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Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed. Employing a targeted RNAi screen, we identified the ubiquitin ligase BIRC2 (cIAP1), a repressor of the noncanonical NF-κB pathway, as a potent negative regulator of LTR-dependent HIV-1 transcription. Depletion of BIRC2 through treatment with small molecule antagonists known as Smac mimetics enhanced HIV-1 transcription, leading to a reversal of latency in a JLat latency model system. Critically, treatment of resting CD4+ T cells isolated from ART-suppressed patients with the histone deacetylase inhibitor (HDACi) panobinostat together with Smac mimetics resulted in synergistic activation of the latent reservoir. These data implicate Smac mimetics as useful agents for shock-and-kill strategies to eliminate the latent HIV reservoir., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Mental health clinicians can experience problems communicating distressing diagnostic information to patients and their families, especially about severe mental illnesses such as schizophrenia. Evidence suggests that interpersonal communication skills can be effectively taught, as has been demonstrated in the specialty of oncology. However, very little literature exists with respect to interpersonal communication skills training for psychiatry. This paper provides an overview of the communication skills training literature., Conclusions: The report reveals significant gaps exist and highlights the need for advanced communication skills training for mental health clinicians, particularly about communicating a diagnosis and/or prognosis of schizophrenia. A new communication skills training framework for psychiatry is described, based on that used in oncology as a model. This model promotes applied skills and processes that are easily adapted for use in psychiatry, providing an effective platform for the development of similar training programs for psychiatric clinical practice., (© The Royal Australian and New Zealand College of Psychiatrists 2015.)

There are conflicting data regarding the effect of digoxin use on mortality in patients with atrial fibrillation (AF) or with congestive heart failure (CHF). The aim of this meta-analysis was to provide detailed analysis of the currently available study reports. We performed a MEDLINE and a COCHRANE search (1993-2014) of the English literature dealing with the effects of digoxin on all-cause-mortality in subjects with AF or CHF. Only full-sized articles published in peer-reviewed journals were considered for this meta-analysis. A total of 19 reports were identified. Nine reports dealt with AF patients, seven with patients suffering from CHF, and three with both clinical conditions. Based on the analysis of adjusted mortality results of all 19 studies comprising 326 426 patients, digoxin use was associated with an increased relative risk of all-cause mortality [Hazard ratio (HR) 1.21, 95% confidence interval (CI), 1.07 to 1.38, P < 0.01]. Compared with subjects not receiving glycosides, digoxin was associated with a 29% increased mortality risk (HR 1.29; 95% CI, 1.21 to 1.39) in the subgroup of publications comprising 235 047 AF patients. Among 91.379 heart failure patients, digoxin-associated mortality risk increased by 14% (HR 1.14, 95% CI, 1.06 to 1.22). The present systematic review and meta-analysis of all available data sources suggest that digoxin use is associated with an increased mortality risk, particularly among patients suffering from AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Many tumors become addicted to autophagy for survival, suggesting inhibition of autophagy as a potential broadly applicable cancer therapy. ULK1/Atg1 is the only serine/threonine kinase in the core autophagy pathway and thus represents an excellent drug target. Despite recent advances in the understanding of ULK1 activation by nutrient deprivation, how ULK1 promotes autophagy remains poorly understood. Here, we screened degenerate peptide libraries to deduce the optimal ULK1 substrate motif and discovered 15 phosphorylation sites in core autophagy proteins that were verified as in vivo ULK1 targets. We utilized these ULK1 substrates to perform a cell-based screen to identify and characterize a potent ULK1 small molecule inhibitor. The compound SBI-0206965 is a highly selective ULK1 kinase inhibitor in vitro and suppressed ULK1-mediated phosphorylation events in cells, regulating autophagy and cell survival. SBI-0206965 greatly synergized with mechanistic target of rapamycin (mTOR) inhibitors to kill tumor cells, providing a strong rationale for their combined use in the clinic., (Copyright © 2015 Elsevier Inc. All rights reserved.)

For many patients with symptomatic atrial fibrillation, cardioversion is performed to restore sinus rhythm and relieve symptoms. Cardioversion carries a distinct risk for thromboembolism which has been described to be in the order of magnitude of 1 to 3 %. For almost five decades, vitamin K antagonist therapy has been the mainstay of therapy to prevent thromboembolism around the time of cardioversion although not a single prospective trial has formally established its efficacy and safety. Currently, three new direct oral anticoagulants are approved for stroke prevention in patients with non-valvular atrial fibrillation. For all three, there are data regarding its usefulness during the time of electrical or pharmacological cardioversion. Due to the ease of handling, their efficacy regarding stroke prevention, and their safety with respect to bleeding complications, the new direct oral anticoagulants are endorsed as the preferred therapy over vitamin K antagonists for stroke prevention in non-valvular atrial fibrillation including the clinical setting of elective cardioversion.

Objective: This research sought to gain insight into the processes used by clinicians to discuss a schizophrenia diagnosis with patients/families, with the aim of informing the development of a communications skills training program., Methods: A generic qualitative methodological approach was used. Sixteen mental health clinicians were recruited. Semi-structured individual interviews were used to explore their perceptions and experiences communicating a schizophrenia diagnosis. Interviews were recorded, transcribed, and thematic analysis undertaken., Results: There were five key themes relating to the process of communication about a diagnosis of schizophrenia: (1) orientation to patient care, (2) planning of communication, (3) the impact of team leadership and inter/intra-professional functioning on communication tasks, (4) the roles of different clinicians in communicating about diagnosis and treatment, and (5) time and resource deficiencies. Despite expressing care and concern for vulnerable patients and embracing the concept of multidisciplinary teams, communicating diagnostic information to patients and families was generally unplanned for, with little consistency regarding leadership approaches, or how the team communicated diagnostic information to the patient and family. This contributed to tensions between different team members., Conclusion: The findings demonstrated a number of issues compromising good communication around a schizophrenia diagnosis, both in terms of clinician skill and clinical context, and support the importance of education and training for all members of the multidisciplinary team about their role in the communication process.

Objective: Important gaps are observed in clinicians' communication with patients and families about psychiatric disorders such as schizophrenia. Communication skills can be taught, and models for education in these skills have been developed in other fields of medicine, such as oncology, providing a framework for training communication skills relevant to psychiatric practice. This study evaluated a pilot communication skills education program for psychiatry trainees, focusing on discussing schizophrenia diagnosis and prognosis., Method: Communication skills training modules were developed based on an existing theoretical framework (ComSkil), adapted for discussing a schizophrenia diagnosis and prognosis. Pre-post training rating of self-reported confidence in a range of communication tasks was obtained, along with trainee views on the training methods., Results: Thirty-eight participants completed the training. Significant improvements in confidence were reported post training for discussing schizophrenia prognosis, including an increased capacity to critically evaluate their own communication skills. Participants reported high levels of satisfaction with the program., Conclusion: This preliminary study provides support for the translation of a well-established educational model to psychiatric training addressing core clinical communication tasks and provides the foundation for the development of a more comprehensive evaluation and an extended curriculum regarding other aspects of care for patients with schizophrenia: ongoing management and recovery, dealing with conflict, and conducting a family interview.

Background: Despite widespread acceptance of the principle that patients should be informed about their diagnosis, many clinicians are reluctant to provide a diagnosis of schizophrenia. This study examines family caregivers' experiences of the communication of a schizophrenia diagnosis and related information., Methods: A generic qualitative methodological approach was used. In all, 13 family caregivers were recruited in regional New South Wales, Australia. Semi-structured interviews were used to explore their experiences and perceptions of discussing the diagnosis, prognosis and treatment of schizophrenia with mental health professionals. Interviews were recorded, transcribed, codes generated and thematic analysis undertaken., Results: Family caregivers described long and difficult pathways to being given a diagnosis, haphazard means of finding out the diagnosis, high unmet needs for information, exclusion from the medical care process and problematic communication and general interactions with mental health clinicians. Caregivers were unanimous about the importance of receiving a timely diagnosis, for them and their relative with schizophrenia., Conclusion: Family caregivers are an integral part of the mental health-care system, and they should be included early in discussions of diagnosis and treatment of a person with schizophrenia. Their perspectives on communicating a diagnosis of schizophrenia provide important information for communication skills training of psychiatrists and other mental health professionals., (© The Author(s) 2014.)

Objective: The aim of this research was to explore mental health clinicians' experiences and perceptions of discussing a diagnosis of schizophrenia with their patients. The results of this research will inform a communication skills training program for psychiatry trainees., Methods: Semistructured interviews were conducted with 16 mental health clinicians from public mental health services in New South Wales, Australia. Interviews were recorded and transcribed for qualitative analysis., Results: Although most clinicians supported the need to give patients a named diagnosis of schizophrenia, most gave multiple reasons for not doing so in practice. The reasons given centered on concerns for the patient; they included fear of making an incorrect diagnosis, fear of the patient's distress, and harm from stigma., Conclusions: Mental health clinicians need to reflect on their own feelings, examine personal identification with their patients, and recognize the subtle interplay of hope and pessimism in their communication of a schizophrenia diagnosis.

A practical and efficient method for the synthesis of substituted 2-aminopyridines from pyridine N-oxides is reported. Yields of purified, isolated products of up to 84% are observed for the one-pot, two-step process. The reaction involves an in situ deprotection of an isolable N-formylaminopyridine intermediate and facilitates the synthesis of 2-aminopyridines for which other methods fail.

TNF-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent because it shows apoptosis-inducing activity in transformed, but not in normal, cells. As with most anticancer agents, however, its clinical use is restricted by either inherent or acquired resistance by cancer cells. We demonstrate here that small-molecule SMAC mimetics that antagonize the inhibitor of apoptosis proteins (IAP) potently sensitize previously resistant human cancer cell lines, but not normal cells, to TRAIL-induced apoptosis, and that they do so in a caspase-8-dependent manner. We further show that the compounds have no cytotoxicity as single agents. Also, we demonstrate that several IAP family members likely participate in the modulation of cellular sensitivity to TRAIL. Finally, we note that the compounds that sensitize cancer cells to TRAIL are the most efficacious in binding to X-linked IAP, and in inducing cellular-IAP (cIAP)-1 and cIAP-2 degradation. Our studies thus describe valuable compounds that allow elucidation of the signaling events occurring in TRAIL resistance, and demonstrate that these agents act as potent TRAIL-sensitizing agents in a variety of cancer cell lines.

A series of novel, potent antagonists of the inhibitor of apoptosis proteins (IAPs) were synthesized in a highly convergent and rapid fashion (≤6 steps) using the Ugi four-component reaction as the key step, thus enabling rapid optimization of binding potency. These IAP antagonists compete with caspases 3, 7, and 9 for inhibition by X chromosome-linked IAP (XIAP) and bind strongly (nanomolar binding constants) to several crucial members of the IAP family of cancer pro-survival proteins to promote apoptosis, with a particularly unique selectivity for melanoma IAP (ML-IAP). Experiments in cell culture revealed powerful cancer cell growth inhibitory activity in multiple (breast, ovarian, and prostate) cell lines with single agent toxicity at low nanomolar levels against SKOV-3 human ovarian carcinoma cells. Administration of the compounds to human foreskin fibroblast cells revealed no general toxicity to normal cells. Furthermore, computational modeling was performed, revealing key contacts between the IAP proteins and antagonists, suggesting a structural basis for the observed potency.

Herein we report the discovery and SAR of a novel metabotropic glutamate receptor 3 (mGlu(3)) NAM probe (ML289) with 15-fold selectivity versus mGlu(2). The mGlu(3) NAM was discovered via a 'molecular switch' from a closely related, potent mGlu(5) positive allosteric modulator (PAM), VU0092273. This NAM (VU0463597, ML289) displays an IC(50) value of 0.66 μM and is inactive against mGlu(5)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Organ transplantation can provide important treatment benefits in a variety of situations. While a number of live donor procedures are now possible, procurement of organs from dead donors remains the mainstay of transplant programmes. However, cadaveric donation rates remain much lower than anticipated, and some patients who receive organs struggle to adapt to their new body. The reasons for this are not entirely explained by rational or logical means. This paper uses concepts drawn from magical thinking to try to explain some of the less apparent issues at play within the process of cadaveric organ transplantation, including both the donation and receiving of organs. Three themes are explored as potentially relevant: superstitions and rituals around death and the dead body, incorporation and the meanings attached to the transplanted organ, and survivor guilt. All three are shown to be relevant for some part of the transplantation process in at least a minority of cases. It is therefore suggested that focusing not only on the logical and scientific, but also on the ambiguous and magical may enhance the organ donation process and thus increase donation rates and the psychological adjustment of transplant recipients.

Objective: The aim of this paper was to investigate key concerns of overseas trained psychiatrists (OTPs) in Australia and New Zealand surrounding the assessment of their qualifications and their experience of the Fellowship examination process., Method: A survey of OTPs progressing towards Fellowship of the Royal Australian and New Zealand College of Psychiatrists (RANZCP) was conducted using an online survey instrument. The survey aimed to explore OTPs' views regarding the key issues encountered in their progression to Fellowship and to gauge their level of satisfaction with a range of RANZCP support initiatives., Results: Important areas of concern were elicited across a variety of domains, including the examination process itself, issues around immigration, and differences in professional culture and language. The message to the RANZCP was that there were still important areas of dissatisfaction relating to measures taken to address these concerns., Conclusions: The authors recommend specific courses of action to address areas where more support is required, and suggest additional areas where more research is needed.

The efficient, scalable preparation of both enantiomers of 2-(1-hydroxy-2-oxocyclohexyl)acetic acid in enantiomerically pure form is reported using environmentally benign conditions in 30% overall yield (6 steps) for the (S)-isomer, in 27% (7 steps) for the (R)-isomer, from cyclohexanone.

By assessing a group of adults who grew up in a household with a parent affected by Huntington's disease (HD), the authors explored the hypothesis that HD causes major disruption in family life. High rates of family dysfunction were reported. Adverse parenting in the form of parental and maternal overcontrol and paternal abuse were endorsed for both the HD-positive and HD-negative parent. These results illustrate the impact on all members of a family coping with HD. They are particularly stark, given the overall psychological health of the sample, and suggest that there is an urgent need to use a family perspective when assessing the need for psychosocial intervention in HD.

Objective: To overview the field of psychotherapy in the medically ill. Rather than attempting a systematic review of this very extensive area, the article seeks to capture some of the main threads and issues of importance., Method: The subject is looked at under four headings: (i) which illnesses have attracted research interest in psychotherapy; (ii) which outcome measures have been chosen; (iii) which modes of intervention have been used; and (iv) finally a review of the methodology and the results obtained., Results: Some illnesses have attracted much more psychotherapeutic interest than others; the differences are haphazard. Outcome measures on the whole have focused on coping with illness and psychological distress, with a smaller number looking at disease outcome. Only short-term changes have been sought in the main. The most commonly used modalities of therapy have been cognitive-behavioural; additionally, supportive information-giving and group therapy have been trialled. Benefit in terms of all these have been reported, but the majority of studies are weakened by major methodological shortcomings., Conclusion: There is an overall paucity of well-designed studies that clearly demonstrate psychotherapy as an efficacious treatment in the medically ill. The field is hampered by the lack of a clear conceptual thread recognizing the long-term and diverse experience of patients with medical illness and relating this to the question of the part psychotherapy should play. Future work needs to concentrate on appropriate selection of patients who might benefit, as well as including a wider range of more clinically relevant outcome measures and more stringent methodology.

Background: The Renal Transplant Advisory Committee has recently approved nondirected kidney donation. If ratified at state level, it will allow volunteers to anonymously donate a kidney to any patient on the transplant waiting list. General practitioners, as well as more specialised services, may be approached by patients wishing to make such donations., Objective: This article summarises the scant literature on nondirected donation., Discussion: Contrary to commonly held beliefs, this type of donor may not necessarily exhibit psychopathology, and this form of donation may raise fewer ethical concerns than are raised by living related donors.

Objective: The aim was to design and run a three-session training module for psychiatric registrars on professional practice with particular emphasis on boundary setting. This included the concept of boundary transgression, an understanding of how it occurs and how it may be avoided., Method: Drawing on North American experience a curriculum was designed and trialed for trainees at all levels. A variety of media were employed to present a range of common clinical and professional issues. Evaluated were trainee satisfaction, trainee responses to target vignettes at the beginning and at the end of the course, and supervisor awareness and involvement in the process., Results: High attendance and high satisfaction ratings in most areas confirmed that a course such as this is attractive and relevant for psychiatric trainees. Vignette responses suggested some change may have occurred by the end of the course, with a more limited tendency to avoid potentially challenging situations and a higher capacity to explore them. Supervisor involvement remains largely unaddressed despite interest and enthusiasm., Conclusion: The area of interpersonal relatedness in psychiatry, including the issue of sexual attraction and the possibility of sexual misconduct, can be introduced as a training package in a way which is acceptable to trainees and their supervisors in an Australian setting. The impact of the training module on actual registrar behaviour is uncertain.

Objective: Levels of psychological distress, social support factors, and emotional adjustment to illness were measured in a sample of patients with severe asthma. These were then examined in terms of their interrelationships and their ability to predict self-management knowledge., Method: A sample of 80 patients was recruited from a hospital-based asthma clinic designed for patients with severe asthma. Thirty-four percent of consecutive attenders approached took part. Morbidity and asthma management were recorded from case records. Anxiety, depression, social support, emotional adjustment to asthma and asthma knowledge were measured using self-report instruments selected for their acceptability and ease of administration., Results: Twenty-five percent of the sample had possible or definite caseness for anxiety; 10.3% had possible or definite caseness for depression. Twenty-five percent had inadequate social support in some way. Three independent attitudinal factors were found: emotional maladjustment to asthma, the doctor-patient relationship, and asthma-related stigma. Level of asthma knowledge was very low. None of the measures of psychosocial function chosen were predictive of asthma knowledge., Conclusions: Levels of asthma knowledge were dangerously low, despite apparently adequate educational initiatives. In addition, patients with severe asthma have high levels of distress, particularly of anxiety, even between attacks. Their attitudes to their illness are multifactorial, and are significantly correlated with emotional distress, morbidity indices and some demographic factors. While this may point the way to interventions designed to relieve patients' distress, the hypothesis that this might in turn relate to practical asthma knowledge was not confirmed.

Objective: To examine the grief reactions that may result in patients after a death occurs within a treatment setting for chronic illness, and in particular to look at the applicability of the concept of survivor guilt in these situations., Clinical Picture: Two patients with endstage renal disease are described. Both presented states of pathological grief for fellow patients. Vulnerability existed in both patients in terms of previous unresolved mourning and in terms of strong feelings of comradship with the dead patients. Both demonstrated features reminiscent of what has been termed the 'survivor syndrome'., Treatment: The treatment involved supportive psychotherapy allowing exploration of grief and its relationship to current psychosomatic crises., Outcome: Supportive psychotherapy successfully aided the resolution in one patient and made some difference in the other., Conclusion: The impact of death within a treatment unit is emphasised. Surviving patients may have significant distress relating to such bereavement and may need appropriate intervention.

Aim: While asthma education increases knowledge, it is less clear whether education influences actual patient behavior. To determine whether there are differences between asthma self-management knowledge and the actual behavior of patients during an acute severe asthma attack and to determine which clinical and psychosocial factors are associated with knowledge and behavior., Methods: Validated hypothetical scenarios describing the development of life-threatening asthma and patients' reported actual behavior were scored (out of 25) using a system based on Thoracic Society of Australia and New Zealand and British Thoracic Society criteria., Results: In 137 patients admitted to the hospital with severe asthma, the pattern of the index attack was slow onset (> or = 6 h) in 96%. The score for the hypothetical attack (knowledge) was 13.8 +/- 4.6, while that for the timeline (behavior) was 10.2 +/- 3.9 (p < 0.001) with 56% and 84%, respectively, having a score of less than 15 (regarded as inadequate). Certain components showed marked discrepancy (eg, appropriately seeking medical help 82% vs 52% (p < 0.001) and calling ambulance 61% vs 23% (p < 0.001). Factors such as physician-patient relationship, previous asthma morbidity, availability of peak flowmeter, action plan, and oral steroids correlated positively with both measures. Knowledge was negatively associated with being non-European, with anxiety, pessimism, and stigmatization. Behavior (but not knowledge) was negatively associated with lack of knowledge of what to do in the index attack, previous emotional counseling, and business failure. Those factors associated with the difference between knowledge and behavior scores (knowledge-behavior gap) were being non-European, anxiety, pessimism, and stigmatization, concerns about medical costs, and the only income for the household being a Social Security benefit., Conclusion: There are marked differences between patients' self-management knowledge and their actual behavior, particularly in terms of potentially life-saving actions. Psychological, health-care, and socioeconomic factors have a powerful and differential influence on knowledge and behavior. Improved understanding of the discrepancies between knowledge and behavior and which factors influence them may lead to more effective asthma educational interventions.

Aims: To develop an instrument for the measurement of, and to determine the level of, practical knowledge of self-management of acute asthma., Methods: Eighty patients with moderate/severe asthma attending a hospital-based asthma clinic responded to an interviewer-administered questionnaire. Subjects were asked to describe the action they would take in response to each of two hypothetical evolving attacks: (1) one of gradually increasing severity and (2) the other developing rapidly. Responses were scored according to the appropriateness of actions taken relevant to the stage of the attack. Transcripts of the responses were scored independently by three of the investigators according to a system based on Thoracic Society of Australia and New Zealand (TSANZ) and British Thoracic Society (BTS) consensus statements on asthma management. A 25-point scale was used on which 0 represented a total lack of appropriate responses and a score of 25 was an optimal response., Results: Interrater and intrarater reliability were excellent. Mean (+/- SD) scores for the slow and rapid onset attacks were 12.8 +/- 4.0 and 13.9 +/- 4.8, respectively. The scores for the two scenarios were predicted by each other (p = 0.002) and by the interviewer's rating of asthma management knowledge (p = 0.0004, p = 0.0001), but not by age, sex, race, previous asthma morbidity, depression, or anxiety. In both scenarios, most patients indicated that they would increase inhaled beta-agonist (85% for slow-onset scenarios and 94% for rapid-onset scenarios, respectively) and use their action plan and/or seek urgent medical advice at an appropriate time (74% and 70%). Although some would measure peak expiratory flow (PEF) initially (54% and 30%), only a minority would continue to monitor PEF in the context of worsening acute asthma (30% and 24%). When a severe life-threatening situation was described, only 50% and 64%, respectively, indicated that they would call emergency services., Conclusions: Scenarios describing hypothetical asthma attacks are a useful and reproducible method of assessing practical knowledge of self-management of acute asthma. Patients presented with scenarios frequently made errors in their hypothetical responses. The errors made with scenarios, which parallel errors reported in real clinical situations, occurred despite the fact that this patient population had received considerable education and training about how to manage asthma. Most indicated they would not monitor PEF even in an exacerbation of asthma and would not call emergency services despite life-threatening asthma. These scenarios may allow us to explore the gap between knowledge about treatment and actual practice, and perhaps to help close that gap and thus reduce asthma morbidity and mortality.

Discussions on the role of self-disclosure during times of personal crisis have been mostly confined to the theoretical. Little clinical material has been published. For the writer, this lack contributed further to the sense of loneliness following bereavement, and to uncertainty in terms of how to provide adequate information to patients while protecting herself at a time of great vulnerability. Using case vignettes, the impact of a therapist's bereavement on patients treated in an outpatient consultation-liaison service is explored. Four patients are described--one woman and two men with very serious physical conditions bringing their own frailty and death very near, and one woman with a psychophysiological condition as part of a borderline personality disorder. The impact of personal crisis is discussed, in an attempt to review how such a situation should be handled, and particularly whether and how patients should be informed.

Objective: Was to construct a classification system of the body image specifically relevant to patient experience of chronic physical disorder., Method: To review both previous writings on body image and also data on psychosocial factors relevant to a variety of chronic illnesses. From this were derived four component parts of body image: comfort, competence, appearance and predictability. These are discussed in general and disease-specific terms., Results: Using this format, a classification system is offered. This is intended to be simple enough for routine clinical use and yet to offer some insight into body experience. An example is given., Conclusion: Separating out the aspects of body image relevant to physical illness provides a clinically useful classification system. Further work is needed to determine its applicability as a research tool.

Two cases of mania in homosexual men with AIDS are presented. Particular emphasis is placed on the psychodynamic and psychosocial factors thought to be aetiologically significant. AIDS is seen both as an example of a terminal illness, and also as creating unique difficulties. It is suggested that integrative rather than reductionist thinking is needed in cases which under DSM-III-R would simply be classified as "organic mood disorder", that is, that all causal and contributory factors need to be considered in affective disorder occurring in the physically ill.

To investigate the importance of body image concerns relating to hand appearance in rheumatoid arthritis, a questionnaire was devised and administered to 80 female out-patients. Subjective judgements of hand attractiveness, feelings about hands, and behaviours relating to hand adornment and concealment were sought. Objective ratings of hand attractiveness were obtained from photographs taken at this time of the women's hands. Factor analysis indicated four principal orthogonal factors describe these body image items. Evaluative and affective elements were found to be independent of each other. The hypothesis that body image, thus rated, is relevant to desire for reparative hand surgery was tested using a two-stage general linear modelling procedure. Body image concerns, particularly negative feelings about hands, emerged as significant predictors of desire for surgery, and remained significant after the removal of variance accounted for by duration of arthritis, age, grip strength and objectively rated hand attractiveness. It is suggested that in rheumatoid arthritis, self-perception of hands and the associated emotional response, may be a covert agenda in women's decision to have surgery, and need specific clinical consideration.

Methylphenidate was administered to each of 12 adult volunteers in a double-blind, placebo-controlled, crossover study for purposes of comparison with previous studies in hyperactive children. Statistically significant changes occurred only on a minority of measures, but the results were generally in the direction of facilitated performance, reduced physical activity and increased emotional responsivity. As these results are similar to those in hyperactive and normal children, this appears to support the contention that stimulant drug effects in hyperactive children are not paradoxical or atypical.