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Therapeutic drug moni to women's health center plainfield il generic arimidex 1mg on-line ring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection breast cancer 2b generic arimidex 1mg with visa. Treatment practices women's health yearly check up quality arimidex 1 mg, outcomes menstrual games cheap arimidex 1 mg on line, and costs of multidrug-resistant and extensively drug-resistant tuberculosis, United States, 2005–2007. Intramuscular injection: an integrative research review and guideline for evidence based practice. Strategies for reducing treatment default in drug-resis tant tuberculosis: systematic review and meta-analysis. Guidelines for preventing the transmission of Mycobacte rium tuberculosis in health-care settings. Tuberculosis transmission by patients with smear-negative pulmonary tuberculosis in a large cohort in the Netherlands. Tuberculosis and Airline Travel: Guidelines for Prevention and Control, 2nd Edition. Interruptions in supplies of second-line antituberculosis drugs—United States, 2005–2012. Medications should not be withheld in anticipation of or because of fear of a reaction. Patients should know that while side effects may be inevitable, they will be addressed and treated as aggressively as possible. Most patients will be willing to continue medication despite side effects when: 1) they understand the beneft of the medication; 2) they know that many of these symp to ms improve after the frst several weeks; and 3) they are assured that their providers are doing their best to evaluate and address their problems. In some cases, minor drug reactions and discomfort may persist and will have to be to lerated to ensure the success of the regimen. For example, some patients with severe disease and extensive resistance may need an aminoglycoside to ensure cure. Nausea and vomiting are most often reported, but abdominal cramps and increased fatulence may be equally troubling. Nausea, vomiting, and anorexia are also consistent with possible hepa to to xicity, so if these symp to ms develop, liver enzymes and to tal bilirubin should be checked. Obtain urgent imaging to eval uate for hydrocephalus, and neurosurgical consultation if indicated. Patients may to lerate one of these two drugs, but many do not to lerate both to gether. Advise the patient that this is a test to determine which drug is causing side effects and that the drug will be reintroduced at a lower dose and slowly increased to a therapeutic dose. Most reports noting effcacy at 300 mg daily were in patients who had the dose decreased after a period of time on the 600 mg dose. Trying another agent may be helpful in some patients when the previously listed options do not work or are not available in your pharmacy. This can easily be done during hospitalization, but may represent a challenge in the community setting. Avoid using antacids or sucralfate within 2 hours of the dose of fuoro quinolones because these agents may interfere with fuoroquinolone absorption. Try acetaminophen with caution as it may increase the risk of hepa to to xicity from other antituberculous medications. This is an easier choice if an adequate regimen can be designed without the medication, but if it leaves the patient with a regimen likely to fail, some nausea and even vomiting may need to be to lerated, at least in the initial period of treatment. This usually improves after the frst several weeks, but may persist in part for the duration of therapy. This may be used intermittently, especially when patients need to attend social functions or return to work. However, there is overlap in the pattern of liver injury caused by these drugs, and all individually or in combination may contribute to hepa to to xicity. If at least 3 medications remain in the treatment regimen that are not hepa to to xic, then these can be continued in the face of elevated liver function tests. These effects may resolve after the frst several weeks of therapy with out s to pping medications. If the reaction is mild, continue treatment and treat the rash and pruritus symp to matically. Drugs should not be continued if there are systemic symp to ms, fever, urticaria, mucous membrane involvement, blistering of the skin, edema of the lips or eyes, or wheezing or compromise of the airway. Evaluate other potential etiologies of rash and pruritus: • Scabies and insect bites may masquerade as a drug rash. Consider lib eral use of lotions, such as petroleum jelly and lanolin (may be purchased in a feed supply s to re where it is less expensive). Lichenoid drug reactions Pruritic, fat- to pped, violaceous papules may occur anywhere, but most commonly involve the wrists, shins, and back. Differentiation from lichen planus can be made by a biopsy showing eosinophilic infltra tion. Hives and urticaria Hives and urticaria may be caused by essentially any drug in an anti-tuberculosis treat ment regimen. Following desensitization, medications should continue to be given 7 days a week for the remainder of therapy. If the initial dose is well to lerated, give 25 mg of Benadryl (but not prednisone) 30 minutes prior to the second dose. Premedication does not prevent a rash but typically makes the reaction less severe and may blunt associated systemic effects, especially the most serious ones. Some patients may beneft from a short course of low-dose steroids if the resulting clinical reaction is only a mildly pruritic rash. Rechallenge should always be accomplished in a set ting where a healthcare provider can respond to the reaction. If a test dose of any drug causes a reaction, that drug should be discontinued, unless it is deemed essential to the regimen. Once desensitization has been successfully completed, it is essential that the patient take medication 7 days per week for the remainder of treatment to avoid another, possibly more severe, reaction. The patient classically has signs of airway compromise, such as stridor, wheezing, a feeling of the throat being closed, swelling of the to ngue, and hoarseness. Additional signs and symp to ms include shock, urticaria, angioedema, confusion, and pruritus. When there is exten typically presents sive sloughing of skin, to xic epidermal necrolysis is likely. Although most patients with elevated uric acid do not need treatment other than adequate hydration, if there is a need to address elevated uric acid levels, allopurinol should not be used. The rash begins as a morbilliform eruption, but progresses to a diffuse, confuent eruption with infltrative erythema. The rash usually progresses to involve the lower extremities and often involves more than half of the body. Organ involvement most frequently includes the liver but may less frequently involve the kidneys or lungs. Liver involvement may man ifest as liver enlargement with jaundice but most often is asymp to matic. If the offending drug is discontinued, the abnormalities are usually mild and resolve quickly. The skin eruption and other abnormalities generally resolve slowly once the drug is with drawn. It may take more than 2 months before the patient experiences complete resolu tion; remissions and relapses not related to drug therapy may occur. It is sometimes not possible to distinguish a reac tion as due to the addition of a new drug or due to a fare of the underlying reaction. S to pping and starting medications or treating with a weak regimen can lead to drug resis tance and treatment failure, so the balance of preventing harm and providing treatment requires signifcant clinical skill and experience. High potency to pical corticosteroids applied 2 to 3 times daily are preferred to systemic ste roids, but can be used for only 1 to 2 weeks. One of these is a fu-like syndrome that is characterized by fever, chills, headache, and bone pain.

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Table 1 shows the rates of sexual victimiza sexual coercion among young people in Salvador tion menstrual 28 day cycle discount arimidex 1 mg with mastercard, defined here as the number of victims di (Northeast Brazil) was significantly higher than vided by the to breast cancer z11 study buy discount arimidex 1mg on line tal sample breast cancer drug purchase arimidex with a mastercard. Incidence rates tions also found that the South showed the lowest for the previous year varied widely menopause 2 periods a month cheap arimidex 1 mg with visa. Although the majority of the studies had rela • Region tively large samples, most were based on convenience samples (Table 2). Three studies More than a half of the studies were conducted used randomized samples from health service exclusively in the Southeast of Brazil, especially units 25,26,27 and one drew a sample from a vul in Sao Paulo State. Of the nine studies of the five macro-regions of Brazil, and two other held in Brazil’s five major regions, only one drew studies compared data from the Northeast with on a representative sample of the Brazilian pop the South or Southeast (Table 2). Of those 11, ulation 13, a second on a representative sample only four provided data on differences between of high school sophomores 29, and a third on regions. One study found that female and male a stratified sampling of psychiatric patients 30. A sec ticipants are selected according to fixed quotas ond study showed that the to tal rate of 16. Author(s) Data collection Region Sampling Population (n) Age in years year(s) (media) Andrade et al. Saude Publica, Rio de Janeiro, 32(7):e00126315, jul, 2016 8 Winzer L Table 2 (continued) Author(s) Data collection Region Sampling Population (n) Age in years year(s) (media) Nunes et al. In pregnant women, rates was the most frequently used measure for as of sexual victimization during pregnancy varied sessing sexual victimization in Brazilian studies. Twenty-six stud on episodes of physically forced sexual inter ies included women only, four studies men only, course, sexual intercourse under threat, and and 11 studies both women and men (Table 2). The high timization, two studies in the five major regions est previous-year incidence rate was reported by of Brazil found similar rates of lifetime female a sample of university students (38. However, the rates were female and male homo and bisexuals was slight slightly lower in the South (8% in Por to Alegre 42) ly more frequent than in heterosexuals. In the second, the Rates were also considerably higher in economi samples of homo and bisexuals were to o small cally vulnerable areas. A second group of studies aggression by women and men found no significant difference in victimization rates according to skin color 21,30,34,35,36. A third Available data on perpetration of sexual aggres group (four studies) did not test for statistical sion in Brazil are still very limited. A to tal of nine significance and found contradic to ry differenc studies addressed the incidence or prevalence es in rates. Of Asian-descendant and indigenous women re these, two investigated lifetime prevalence of ported higher rates of victimization than white, sexual aggression. Another study found vestigated sexual aggression using different time that white and brown individuals reported high frames, such as in the previous year, after age 14, er rates than black, Asian-descendant, or indig after age 18, during pregnancy, since starting uni enous persons 32. Two studies included female • Definition of sexual victimization respondents only, three studies included men and women, and four studies included men only. The definition of sexual victimization varied Specific social groups were addressed by seven widely (Table 3). The number and wording of studies: university students 14,38,40,43, pregnant questions potentially affected the resulting women 44, men who have sex with men 35, and rates. However, differences World Health Organization Multicentre Study in time frames and whether the aggression was Cad. Saude Publica, Rio de Janeiro, 32(7):e00126315, jul, 2016 10 Winzer L Table 3 Defnition of sexual victimization by studies that investigated the frequency of self-reported sexual victimization in Brazilian samples Author(s) Operationalization of sexual victimization Andrade et al. In order to assess self-reported perpetration, they used parallel versions for perpetration from the items described in this table; *** this paper also addressed perpetration. For the perpetration version, two questions were asked: (1) Have you ever forced your partner to have sexual relations when she did not want to fi Table 4 Prevalence and incidence of self-reported perpetration of sexual aggression in Brazilian samples. More information on the operationalization of perpetration of sexual aggression, region and characteristics of the sample can be found in Tables 2 and 3. Differences in perpetration rates according to sexual orientation and skin color were also ad dressed. One study found that female and male Discussion bisexuals and male homosexuals were more likely to report perpetration than heterosexuals. Sexual aggression has attracted increasing po However, the authors did not test for statisti litical attention and scientific research in Brazil cal significance 14. Saude Publica, Rio de Janeiro, 32(7):e00126315, jul, 2016 12 Winzer L ers have identified sexual victimization in the by official medical records 2, according to which, general population and in community and clini in Brazil, white and brown women are the most cal samples. Brazilian the current article reviewed studies on the studies found the highest incidence rates of vic incidence and prevalence of self-reported sexual timization in this group. However, it was not pos aggression and victimization among women and sible to say with certainty that this group is at men in Brazil. Despite the heterogeneity of meth greater risk than the general population, for two ods and limited comparability of data, the review reasons: the two samples were not compared to showed that sexual aggression is a pervasive each other, and the rates were obtained by dif problem in young adulthood 3,14,29,38,39,40,43 and ferent measures. Higher victimization rates in is much more prevalent than identified by offi university students could be attributed to the cial data. For ex in rates among studies that used the same instru ample, instead of asking, “Have you ever been ment could be attributed to other fac to rs, such as rapedfi Nevertheless, an increasing or made me have oral sex with them without my number of studies have addressed male victim consent”) 16. Studies on self-report struments is that they assessed coercive acts that ed perpetration are still few, especially among were usually neglected by other studies, such as women. However, the percentage of victimization her/himself) 16, and refusal by the partner to use was higher in male homosexuals and bisexu a condom during sexual intercourse 38. Still, regardless inclusive and meticulous definitions of sexual ag of sexual orientation, victimization in men has gression may partly explain the inflated rates in been ignored for some time by researchers and university students. Male victimization does not mini the results of the present review allow iden mize or justify male aggression against women, tifying some gaps in Brazilian research on sexual which is highly prevalent and appears to have aggression. First, the majority of studies in Brazil more severe consequences than the opposite relied on convenience samples, which provide case 47, but this shows that public health profes results that cannot be generalized to the over sionals should be aware of male victimization all Brazilian population. Random selection of and that health services should be prepared to participants from a health service or from a vul receive and treat male victims. Randomly chosen respondents definition of skin color, especially in a country from a single health service makes up a repre like Brazil with a strong his to ry of miscegenation. Some studies only adopted a dicho to my (white Besides, more than a half of the studies were con vs. The re tutes are concentrated, revealing the imbalance view’s findings also contrast with those provided of available information on self-reported sexual Cad. Third, many studies were unable victimization in both men and women, taking to differentiate between sexual abuse (before age sexual orientation and skin color in to consider 14) and sexual aggression in adulthood (after age ation; (5) studies that address incidence of sexual 14). Fourth, in addition to the lack of that rates can be directly compared to the official information on time frame, location, and sample data on rape in Brazil; (6) studies that confirm age, some studies failed to provide clear informa if, and explain why, specific social groups. Oth homosexuals and bisexuals, and university stu er studies applied only a single or a few screen dents) may have higher vulnerability for sexual ing questions. From a pub although such behaviors would legally qualify lic health perspective, sexual aggression should as rape. The use of behaviorally specific descrip be unders to od as a continuum of violence that tions of coercive acts prevents ambiguity and en threatens the well-being of victims. If sexual aggression is underreported, tive samples of the Brazilian population, identi numerous victims remain subjected to physical, fying the differences across the five major geo mental, and social trauma without receiving any graphic regions; (2) studies that address sexual form of medical, psychological, or legal support. Saude Publica, Rio de Janeiro, 32(7):e00126315, jul, 2016 14 Winzer L References 1. Magnitude sion and victimization in a national sample of e caracterizacao de situacoes de coercao sexual higher education students. J Consult Clin Psychol vivenciadas por jovens de tres grandes capitais 1987; 55:162-70. Chichester: John dimen to das mulheres que sofreram violencia se Wiley & Sons; 2002. Aggress Violent fermeiros sobre o servico de atencao as mulheres Behav 2007; 12:315-28. Reporting and incidence of violence da violencia contra a mulher usuaria de servico de against women in India, 2014. Violencia contra a mu loads/2014/10/Reporting-and-incidence-of-vio lher ou mulheres em situacao de violenciafi Uma lence-against-women-in-India-working-paper analise sobre a prevalencia do fenomeno.

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Treatment with ion to menstrual knee pain order arimidex 1mg with visa phoresis (Hyperhidrosis programme) makes it possible to pregnancy nausea order arimidex from india obtain lasting remission of hyperhidrosis after around ten sessions pregnancy quiz before missed period purchase 1 mg arimidex fast delivery. The remission period can last up to pregnancy 28 weeks order 1 mg arimidex otc six months, and the treatment can be started again when the signs reappear. Pro to col Hyperhidrosis: the frst session will be conducted with the electrical density au to matically provided (by default) of 0. Patient position the patient is seated with the feet or hands immersed in the basin, with the palms or soles resting on the electrodes. Stimulation intensities For these programmes, the intensity increases au to matically after validation (“+” or “–“ key on the fourth channel) of the the desired electrical density selection. Although Taylor has shown that a single 30-minute session can successfully reduce oedema, the efects are short-lived (lasting only about 6 hours). For optimum results, other methods designed to reduce oedema formation (cold therapy, compression bandaging, elevation, etc. The mechanisms by which interrupted direct currents act (consisting of monophasic pulses) are still unclear. Karnes has ruled out a vasoconstric to r mechanism and the most plausible hypothesis is that the currents reduce local protein substrate density by reducing vascular membrane permeability, also preventing the arrangement of protein molecules, or by combining both mechanisms. Parameters Consequently, it is important to A Work with monophasic rectangular pulses delivered at a continuous frequency of 120 Hz. B Place one or more negative electrodes (cathodes) on the swelling and positive electrodes above the swelling. For example, for oedema caused by an ankle sprain, two stimulation channels will be used: two large negative electrodes will be placed on the malleolar and perimalleolar region, and one of the two outputs of each electrode is not used. A large electrode is positioned above the patella, at the level of the quadricipital tendon, and will be connected to the positive poles of the two stimulation channels. Patient position the patient will be placed in the most comfortable position for him or her, with the treated limb elevated. For example, for oedema of the ankle, the patient will be in the supine position, with the lower limbs elevated by about thirty centimetres relative to the plane of the table. Stimulation intensities the Oedema programme begins au to matically with a short test in which the stimulation intensity increases au to matically. The rehabilitation therapist, visually or by palpation, attempts to detect the start of muscular activity. Electrostimulation of denervated muscle fbres, however, is essential insofar as it is the only really efective means of retaining a certain trophicity and limiting the sclerosis phenomenon of these fbres throughout the duration of their possible re-innervation period. Indeed, after many months of being patient, nothing is more frustrating than to fnd functional trouble caused by muscles that are certainly re-innervated but with a sclerosis condition that prevents them from being used satisfac to rily. If stimulation enables the amyotrophy to be limited and sclerosis of the denervated muscle to be avoided during its re-innervation period, it then becomes pointless if there is any hope of re-innervation for the denervated fbres. The choice of form and parameters of the electrical current depend on state of denervation of the muscle: is it completely or partly denervatedfi Therefore, before undertaking any electrostimulation treatment on a denervated muscle, the following two questions should be answered: 1 Is there any hope of re-innervationfi To be able to answer this question, it is essential to have the following three pieces of information: A the date of the injury, B the degree of the injury, C the rate of nerve fbre regeneration. However, with certain muscles, especially if there are only very few innervated fbres left, the really analytical contraction of the muscle is difcult to obtain because of the inevitable activity of the agonist muscles. If no response is observed in spite of signifcant current strengths, the muscle can then be considered as completely denervated; if, on the other hand, a contraction, even of low intensity, is achieved, then the muscle is partly denervated. Practical therapeutic approach It is therefore actually easy to fnd out the two fundamental fac to rs that will guide our therapeutic approach: • There is hope of re-innervation or, on the contrary, denervation is fnal. Situation 2: Partial denervation outside the time It is not possible to avoid atrophy and sclerosis of muscle fbres that are defnitively denervated. Stimulation of these fbres by means of the Denervated programmes is therefore not indicated here. It is possible, however, to work on the innervated part of the muscle, by means of neurostimulation rectangular biphasic micropulses in order to achieve compensa to ry hypertrophy of the innervated fbres. Situation 3: Total denervation within the time Pending possible re-innervation, it is important to prevent atrophy as much as possible and limit the sclerosis phenomenon. Stimulation of muscles deprived of innervation, by means of wide rectangular pulses in the Denervated programmes is the preferred technique here. The ramp to be used to excite specifcally the denervated fbres and not the innervated fbres or the mo to r neurons must be determined. Ramp detection is therefore essential; this will be carried out by the device’s au to matic system with a pulse of 100 ms or, better still, after establishing the accommodation curve that will make it possible to choose possibly a shorter pulse duration. Once the ramp has been established, the device will au to matically adjust the width of the pulse to the intensity used so as to keep the ramp constant (see graph below). These ramped pulses must be balanced in order to have a zero electrical mean so as to avoid chemical burns. Post-traumatic condition 205 acl ligamen to plast 207 rehabilitation of the gluteal muscles following to tal hip replacement 211 rehabilitation of the shoulder 213 1. Adhesive capsulitis 220 cardiac rehabilitation 223 refex sympathetic dystrophy (or complex regional pain syndrome) 226 endorphinic treatment of rachialgia and radiculalgia 231 1. Venous insufciency with oedema 257 treatment of arterial insufciency in the lower limbs 260 1. Despite immense progress in orthopaedic medicine, it is still common practice to have a period of immobilisation of the area concerned, which can be to tal or partial. The result is always a signifcant reduction, in the normal activity of the muscles in the traumatised region. The rapid disuse atrophy which occurs (reduction in the muscle volume and the muscle tissue’s ability to contract) can sometimes compromise the functional future of the patient. The physiological mechanisms involved in the alteration of the diferent muscle fbres under such circumstances are well-known, and therefore extremely specifc treatments can be proposed, which can produce optimum benefts on their own. This standard pro to col is recommended for the majority of cases of functional disuse atrophy. However, this pro to col can be adapted depending on the pathology, the treatment objectives and the speed of the patient’s recovery. The precise location of the mo to r point(s) is easy to ascertain by following the instructions for the indication “Locating a mo to r point” in this manual. This step ensures that the electrodes will be positioned to provide optimum comfort to the patient and optimum efectiveness of the therapy. Consequently, this position must be avoided and the patient should be placed in a position in which the stimulated muscle is in a mid range position. The end of the stimulated limb must be securely tied down so that the electrically induced contraction does not cause any movement. When the patient has difculty in reaching satisfac to ry levels of stimulation energy, it can be useful to ask the patient to add voluntary co-contractions, which improves mediocre spatial recruitment and also makes the stimulation more comfortable. Following a sprain, due to the functional disability, refex inhibition phenomena and immobilisation, these muscles can undergo partial disuse atrophy, a loss of proprioceptive refexes and a considerable loss of strength. Rehabilitation following such an accident must therefore focus essentially on the peroneus muscles in order to prevent recurrences. To fulfl their function optimally, the peroneus muscles must efectively put up resistance to brief and powerful stresses. They must therefore be capable of responding with a powerful, short contraction at that very moment when the stress being applied to the foot risks making the ankle tilt inwards. This aspect of rehabilitation consists of properly performing exercises on classic “balance boards”, such as Freeman boards, a sufcient number of times (number of sessions). Muscle reinforcement: Allows the peroneus muscles to contract with enough strength to oppose the stress applied to the ankle joint. This aspect of rehabilitation consists of producing peroneus muscle contractions using electro-stimulation and using programmes designed for developing explosive force. Only this method is really capable of developing the strength of these muscles efectively, given the impossibility of feasibly being able to carry out active methods with this level of load! A small electrode is placed under the head of the fbula, at the passage of the Common Peroneal nerve. For optimum efectiveness, the positive electrode should preferably be positioned on the mo to r point. In this position, the therapist gradually increases the stimulation energy until a mo to r response is manifested by an eversion of the foot. As soon as this response is obtained (most often after 2 or 3 contractions), the barefoot patient is put in to standing position.

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In older individuals pregnancy vs period purchase genuine arimidex on-line, the disorder is associated with negative health perceptions menstruation cycle pregnancy buy discount arimidex 1mg online, primary care utilization menstruation quiz generic 1mg arimidex, and suicidal ideation women's health clinic quesnel buy arimidex cheap. Risk and Prognostic Fac to rs Risk (and protective) fac to rs are generally divided in to pretraumatic, peritraumatic, and posttraumatic fac to rs. These include lower socioeconomic status; lower education; exposure to prior trauma (especially during childhood); childhood adversity. These include female gender and younger age at the time of trauma exposure (for adults). Finally, dissociation that occurs during the trauma and persists afterward is a risk fac to r. These include negative appraisals, inappropriate coping strategies, and development of acute stress disorder. These include subsequent exposure to repeated upsetting reminders, subse­ quent adverse life events, and financial or other trauma-related losses. Social support (includ­ ing family stability, for children) is a protective fac to r that moderates outcome after trauma. Impaired function­ ing is exhibited across social, inteq:)ersonal, developmental, educational, physical health, and occupational domains. The diagnosis requires that trauma exposure precede the onset or exacerbation of pertinent symp to ms. If severe, symp to m response patterns to the extreme stressor may warrant a sep­ arate diagnosis. Neither the arousal and dissociative symp to ms of panic disorder nor the avoidance, irritability, and anxiety of generalized anxiety disorder are associated with a specific traumatic event. The symp to ms of separation anxiety disorder are clearly related to separation from home or family, rather than to a traumatic event. Comorbid substance use disorder and conduct disorder are more common among males than among females. Exposure to actual or threatened death, serious injury, or sexual violation in one (or more) of the following ways: 1. Note: In cases of actual or threatened death of a family member or friend, the event(s) must have been violent or accidental. Note: this does not apply to exposure through electronic media, television, mov­ ies, or pictures, unless this exposure is work related. Presence of nine (or more) of the following symp to ms from any of the five categories of intrusion, negative mood, dissociation, avoidance, and arousal, beginning or wors­ ening after the traumatic event(s) occurred: Intrusion Symp to ms 1. Recurrent, involuntary, and intrusive distressing memories of the traumatic event(s). Note: In children, repetitive play may occur in which themes or aspects of the traumatic event(s) are expressed. Recurrent distressing dreams in which the content and/or affect of the dream are related to the event(s). Intense or prolonged psychological distress or marked physiological reactions in re­ sponse to internal or external cues that symbolize or resemble an aspect of the traumatic event(s). Inability to remember an important aspect of the traumatic event(s) (typically due to dissociative amnesia and not to other fac to rs such as head injury, alcohol, or drugs). Efforts to avoid distressing memories, thoughts, or feelings about or closely asso­ ciated with the traumatic event(s). Efforts to avoid external reminders (people, places, conversations, activities, ob­ jects, situations) that arouse distressing memories, thoughts, or feelings about or closely associated with the traumatic event(s). Irritable behavior and angry outbursts (with little or no provocation), typically ex­ pressed as verbal or physical aggression to ward people or objects. Duration of the disturbance (symp to ms in Criterion B) is 3 days to 1 month after trauma exposure. Note: Symp to ms typically begin immediately after the trauma, but persistence for at least 3 days and up to a month is needed to meet disorder criteria. Traumatic events that are experienced directly include, but are not limited to, exposure to war as a combatant or civilian, threatened or actual violent personal assault. For children, sexually traumatic events may include inappropriate sexual experiences without violence or injury. A life-threatening illness or debilitating medical condition is not necessarily considered a traumatic event. Medical incidents that qualify as traumatic events involve sudden, catastrophic events. Stressful events that do not possess the severe and traumatic components of events encompassed by Criterion A may lead to an adjust­ ment disorder but not to acute stress disorder. The clinical presentation of acute stress disorder may vary by individual but typically involves an anxiety response that includes some form of reexperiencing of or reactivity to the traumatic event. In some individuals, a dissociative or detached presentation can pre­ dominate, although these individuals typically will also display strong emotional or phys­ iological reactivity in response to trauma reminders. In other individuals, there can be a strong anger response in which reactivity is characterized by irritable or possibly aggres­ sive responses. The full symp to m picture must be present for at least 3 days after the trau­ matic event and can be diagnosed only up to 1 month after the event. Symp to ms that occur immediately after the event but resolve in less than 3 days would not meet criteria for acute stress disorder. Witnessed events include, but are not limited to, observing threatened or serious in­ jury, unnatural death, physical or sexual violence inflicted on another individual as a re­ sult of violent assault, severe domestic violence, severe accident, war, and disaster; it may also include witnessing a medical catastrophe. Events experienced indirectly through learning about the event are limited to close relatives or close friends. Such events must have been violent or accidental—death due to natural causes does not qualify—and include violent personal assault, suicide, se­ rious accident, or serious injury. The disorder may be especially severe when the stressor is interpersonal and intentional. The likelihood of developing this dis­ order may increase as the intensity of and physical proximity to the stressor increase. Commonly, the individual has recurrent and intrusive recollections of the event (Criterion Bl). The recollections are spontaneous or triggered recurrent memories of the event that usually occur in response to a stimulus that is reminiscent of the traumatic experience. Distressing dreams may contain themes that are representative of or thematically re­ lated to the major threats involved in the traumatic event. While dissociative responses are common during a trau­ matic event, only dissociative responses that persist beyond 3 days after trauma exposure are considered for the diagnosis of acute stress disorder. For young children, reenactment of events related to trauma may appear in play and may include dissociative moments. These episodes, often referred to asflashbacks, are typically brief but involve a sense that the traumatic event is occurring in the present rather than being remembered in the past and are associated with significant distress. Some individuals with the disorder do not have intrusive memories of the event itself, but instead experience intense psychological distress or physiological reactivity when they are exposed to triggering events that resemble or symbolize an aspect of the traumatic event. Alterations in awareness can include depersonalization, a detached sense of oneself. Some individuals also report an inability to remember an important aspect of the traumatic event that was presumably encoded. This symp to m is attributable to dissociative amnesia and is not at­ tributable to head injury, alcohol, or drugs. The individual may refuse to discuss the traumatic experience or may engage in avoidance strategies to minimize awareness of emotional reactions. This behavioral avoidance may include avoiding watching news coverage of the traumatic experience, refusing to return to a workplace where the trauma occurred, or avoiding interacting with others who shared the same traumatic experience. It is very common for individuals with acute stress disorder to experience problems with sleep onset and maintenance, which may be associated with nightmares or with gen­ eralized elevated arousal that prevents adequate sleep. Individuals with acute stress dis­ order may be quick tempered and may even engage in aggressive verbal and/or physical behavior with little provocation. Acute stress disorder is often characterized by a height­ ened sensitivity to potential threats, including those that are related to the traumatic ex­ perience. Individ­ uals with acute stress disorder may be very reactive to unexpected stimuli, displaying a heightened startle response or jumpiness to loud noises or unexpected movements.

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As used in this Amendment menopause sleep purchase 1mg arimidex with mastercard, capitalized terms shall have the same meanings set forth in the Agreement menstrual odor causes generic arimidex 1mg on-line, unless otherwise defined in this Amendment menstrual krampus discount 1mg arimidex mastercard. The Agreement is hereby amended by adding the attached “Exhibit A” that is made a part of this Amendment menstruation red tent buy 1mg arimidex overnight delivery. The Agreement is hereby amended by adding the attached “Exhibit B” that is made a part of this Amendment. The Agreement is hereby amended by adding the attached “Exhibit C” that is made a part of this Amendment. These studies will also evaluate potential doses and dosing regimens to optimize the therapy under investigation. Nothing in this Section 2 shall restrict Brickell or its affiliates from negotiating with, soliciting proposals from, entering in to agreements with, or providing information to (x) its-own actual and 2 potential advisors, agents and representatives and/or (y) any third party contract research organization or contract manufacture or other service provider. Kaken acknowledges that Brickell shall have the sole discretion regarding the development of the [***]inside and outside of the Terri to ry and that Brickell may cease development of a [***] at any time if Brickell so determines. In the event of a Change of Control transaction, the following provisions of this Section 2 shall apply: 2. All compounds that were controlled by Brickell’s successor or such successor’s affiliates that were not affiliates of Brickell prior to such Brickell Change of Control (collectively, the “Successor”) shall not be included within the [***]. Compounds that, following such Brickell Change of Control, are developed, made or otherwise acquired or controlled by the Successor without use of Brickell’s Confidential Information (as defined in the Agreement) shall not be deemed [***]. Unless otherwise specified in writing, the mailing addresses of the Parties shall be as described below: If to Brickell: [***] With a copy to : [***] If to Kaken: [***] With a copy to : [***] 3. This Amendment shall be effective as of the date of receipt by Brickell of the Development Miles to ne 1 Payment pursuant to Section 8. At the time Brickell issues the [***], Brickell shall also physically or electronically deliver to Kaken, or provide Kaken access via secure electronic data room (any such delivery method, “make available,” and “made available” shall have a corresponding meaning) all material data related to [***], including from such [***], that Brickell then possesses (the “[***]”). Upon Brickell’s receipt of the [***], Kaken shall have a period of [***] with Brickell [***]concerning the terms of an [***]. At the time Brickell issues the [***], Brickell shall make available to Kaken [***]. Upon Brickell’s receipt of the [***], Kaken shall have a period of [***] (the [***]) to negotiate [***]. Nothing in this Section 2 shall restrict Brickell or its affiliates from negotiating with, soliciting proposals from, entering in to agreements with, or providing information to, (x) its own actual and potential advisors, agents and representatives and/or (y) any third party contract research organization or contract manufacture or other service provider. Licensor and Licensee are each individually referred to herein as a “Party” and collectively referred to as the “Parties. For purposes of this definition, “control” shall mean the ownership of at least fifty percent (50%) of the voting s to ck of such entity or any other comparable equity or ownership interest, or (a) in the absence of the ownership of at least fifty percent (50%) of the voting s to ck of a corporation, or (b) in the case of a non-corporate business entity, possession, directly or indirectly, the power to direct, or cause the direction of, the management and policies of such entity whether through the ownership or control of voting securities, by contract or otherwise. Licensor hereby grants to Licensee an [***], license under the Licensed Patents and Licensed Know-How in the Field within the Terri to ry to [***] Licensed Product. Any sublicense granted by Licensee to any Sublicensee shall be subject to a written sublicense agreement that contains terms and conditions that (a) impose obligations that are comparable to the obligations applicable to Licensee under this Agreement including, but not limited to, the audit rights set forth in Section 3. Without limiting the foregoing, each such sublicense agreement shall provide that Licensor is a third party beneficiary of such sublicense agreement, with the right to enforce the terms thereof in the event that Licensee does not enforce its rights. Licensee shall notify Licensor in writing of the grant of any such sublicense within ten (10) days thereof, which notice shall identify the Sublicensee and shall be accompanied by a copy of the applicable sublicense agreement. The terms of such sublicense agreements, and the identity of all Sublicensees shall be Confidential Information (as defined below) of Licensee. Licensee shall use Commercially Reasonable Efforts to moni to r the performance of any Sublicensee under any sublicense granted pursuant to this Section 2. Licensor shall not be permitted, and shall cause its Affiliates to refrain from the practice of any rights granted to Licensee under this Article 2 in the Field in the Terri to ry during the Term of this Agreement. During the Term of this Agreement, Licensor shall not grant to any third party any right or license whatsoever under the Licensed Patents or Licensed Know-How in the Field. Any new Invention or discovery, whether patentable or not, made solely by Licensee or in combination with any third party, as a result of the exercise of this Agreement, shall be Licensee’s property. The Parties shall reasonably cooperate in any patent application procedures for inventions or discoveries made under this section at Licensee’s expense. Except as expressly set forth herein, this Agreement does not grant to Licensee any right, title, interest, ownership or license by implication, es to ppel or otherwise, to any intellectual property rights of Licensor. Licensee shall use [***] at its own cost and expense to develop a Licensed Product, to conduct all development necessary to obtain regula to ry approval to market such Licensed Product, and to commercialize such Licensed Product, according to the applicable completion date listed in the table below for the Licensed Product. Licensee will deliver to Licensor an annual updated development plan for the Licensed Product (the “Development Plan”) no later than January 31 of each year during the Term. The Development Plan will include, at a minimum, the information listed in Exhibit “B” (“Exhibit B”). Where the Licensee fails to [***] the Licensed Product in accordance with the Development Plan and Diligence Events, and fails to diligently undertake actions to remedy any such deficiency, and where mediation has failed to accomplish a satisfac to ry resolution, the Licensor may consider such failure to be a material breach under this Agreement and shall have the right to terminate this Agreement pursuant to Section 4. On or before the Effective Date of this Agreement, Licensor shall provide Licensee with a copy of all tangible materials and information in its possession related to or involving the Licensed Patents. Such information and materials shall generally include but not be limited to all patent correspondence, patent searches, patent files, patent landscaping, inven to r disclosures, and patent applications and schedules. Licensor shall provide and make available to Licensee all manufacturing information and data, all formulation information and data, and all clinical and pre-clinical data, including to xicity data, whether submitted or not, as part of any Investigative New Drug Application or New Drug Application filing of Licensor or its sublicensees or Affiliates with respect to a Licensed Product subject to provisions of confidentiality. Licensor agrees to use its reasonable efforts to identify and make available inven to rs and any key scientific personnel to discuss research, development and commercialization activities as reasonably required. Each Party will make available, at no cost, data and any reports, including but not limited to full study reports, of any non-clinical and/or clinical study in animals or humans, related to the Licensed Patents and Licensed Know-How, on a confidential basis within sixty (60) days of the generation of same, such that: (i) Licensor may share such data with any other party, on a confidential basis, as background information in respect of any other non-competing application outside of the Field and have the right to reference any or all such data, (ii) Licensee may share such data, on a confidential basis, as background information to its Affiliates, financing sources, and potential inves to rs and have the right to reference any or all such data for 4 development of Licensed Product in the Field only, and (iii) Licensee shall utilize such data to ensure full compliance with the regula to ry authorities and to inform future development of the Licensed Product, provided neither party shall be required to disclose internally developed information to any competi to r without the permission of the developing party. As consideration for the rights and licenses granted by Licensor to Licensee hereunder, Licensee agrees to pay Licensor the following amounts at the following times: 3. Licensee shall pay to Licensor miles to ne payments (each, a “Miles to ne Payment”) as set forth in the following table [***] if and when each Miles to ne Event is achieved. Licensee shall notify Licensor promptly in writing (but in each case within thirty (30) days) of its achievement of each Miles to ne Event. Each Miles to ne Payment (other than Upfront payments) shall be due within sixty (60) days following the achievement of the applicable Miles to ne Event. The activities undertaken and the results achieved from all clinical development efforts shall be made available to Licensor on a confidential basis and in a timely manner, subject to Section 2. Licensee will pay a royalty to Licensor [***] (“Patent Royalty” or collectively, “Patent Royalties”). During the term of this Agreement, should Licensee enter in to any sublicense with an unaffiliated third party (“Sublicensee”) for the sale of Licensed Products (“Sublicensing Agreement”), the rate for Patent Royalties payable to Licensor shall be in accordance with the following schedule based on the patent royalty rate set forth in the Sublicensing Agreement (the “Sublicensee Patent Royalty Rate”): 5 [***] [***] [***] [***] [***] [***] 3. The Royalty on Net Sales of Licensed Products shall be [***] upon a [***] to any [***]. After [***] by Licensee or Sublicensees of a Licensed Product for which a Patent Royalty is payable under this Article 3, Licensee shall make quarterly written reports to Licensor within forty-five (45) days after the end of each calendar quarter, stating in each such report the number, description, Gross Sales, and itemized Net Sales of such Licensed Product sold during the calendar quarter. Simultaneously with the delivery of each such report, Licensee shall pay to Licensor the Patent Royalty, if any, due to Licensor for the period of such report. Such reports shall be Confidential Information of Licensee subject to Article 5, herein. Where any currency conversion is to be made in connection with the calculation of any amounts hereunder, such conversion shall be made using the selling exchange rate for conversion of the foreign currency in to U. In addition to any other rights and remedies of Licensor under this Agreement, any amounts owed to Licensor under this Agreement shall, if not paid when due, accrue interest at a rate that is the lesser of [***]. Licensee shall maintain, and shall cause its Sublicensees to maintain, complete and accurate books and records relating solely to Net Sales of the Licensed Product and any amounts payable to Licensor under this Agreement, which records shall contain sufficient information to permit Licensor to confirm the accuracy of any reports delivered to Licensor hereunder. Licensor shall have the right to inspect Licensee’s books and records as needed in Licensor’s reasonable discretion. The term of this Agreement shall commence on the Effective Date, and shall continue in full force and effect until either (i) termination by either Party in accordance with Section 4. For purposes of this paragraph, “Cause” shall mean any material breach of any material provision of this Agreement by Licensor that is not cured within sixty (60) days after receipt by Licensor of written notice thereof from Licensee or, in the event that cure is not possible within such sixty (60) day period, Licensor shall have taken reasonable steps to ensure that the breach is cured as soon as reasonably possible. Licensor may terminate this Agreement (i) for Cause or (ii) immediately upon written notice to Licensee if Licensee or any Sublicensee brings a patent challenge against Licensor, or assists others in bringing a patent challenge against Licensor (except as required under a court order or subpoena). For purposes of this paragraph, “Cause” shall mean any material breach of any material provision of this Agreement by Licensee that is not cured within sixty (60) days after receipt by Licensee of written notice thereof from Licensor or, in the event that cure is not possible within such sixty (60) day period, Licensee shall have taken reasonable steps to ensure that the breach is cured as soon as reasonably possible; provided, however, that if the material breach is non-payment to Licensor of amounts due, then Licensee shall have sixty (60) days to cure, except in circumstances where there is a good faith dispute between the Parties as to sums due and owing and the Parties are engaged in a dispute resolution process to determine the legitimacy of any demand for sums due and any undisputed amounts are paid in full. Either Party may, by written notice, terminate this Agreement with immediate effect if the other Party: (i) makes a general assignment for the benefit of credi to rs; (ii) files an insolvency petition in bankruptcy; (iii) petitions for or acquiesces in the appointment of any receiver, trustee or similar officer to liquidate or conserve its business or any substantial part of its assets; (iv) commences proceeding involving its insolvency, bankruptcy, reorganization, adjustment of debt, dissolution, liquidation or any other similar proceeding for the release of financially distressed deb to rs under the laws of any jurisdiction; or (v) becomes a party to any proceeding or action of the type described above in (iii) or (iv), and such proceeding or actions remains =dismissed or =stayed for a period of more than ninety (90) days.

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