Politicisation and managerial values: Responses from New Zealand councillors

This study assesses the proposition that politicisation of public sector employment leads to government managers moving away from neutrality values and adopting responsive values. Results of a survey of well over 100 councillors in the New Zealand local government system provided limited support to this proposition. Most councillors report managers adopting neutrality values and combining them with elements from trustee and responsive value types in the area of managerial advice. We argue that although most managers accept the traditional role distribution between councillors and managers a small percentage of managers tend to believe that managers have an obligation to ensure that their view of community interest is heard in the policy process

The Competition of Charge Remote and Charge Directed Fragmentation Mechanisms in Quaternary Ammonium Salt Derivatized Peptides—An Isotopic Exchange Study

Derivatization of peptides as quaternary ammonium salts (QAS) is a promising method for sensitive detection by electrospray ionization tandem mass spectrometry (Cydzik et al. J. Pept. Sci.2011, 17, 445–453). The peptides derivatized by QAS at their N-termini undergo fragmentation according to the two competing mechanisms – charge remote (ChR) and charge directed (ChD). The absence of mobile proton in the quaternary salt ion results in ChR dissociation of a peptide bond. However, Hofmann elimination of quaternary salt creates an ion with one mobile proton leading to the ChD fragmentation. The experiments on the quaternary ammonium salts with deuterated N-alkyl groups or amide NH bonds revealed that QAS derivatized peptides dissociate according to the mixed ChR-ChD mechanism. The isotopic labeling allows differentiation of fragments formed according to ChR and ChD mechanisms

Immune-Complex Mimics as a Molecular Platform for Adjuvant-Free Vaccine Delivery

Protein-based vaccine development faces the difficult challenge of finding robust yet non-toxic adjuvants suitable for humans. Here, using a molecular engineering approach, we have developed a molecular platform for generating self-adjuvanting immunogens that do not depend on exogenous adjuvants for induction of immune responses. These are based on the concept of Immune Complex Mimics (ICM), structures that are formed between an oligomeric antigen and a monoclonal antibody (mAb) to that antigen. In this way, the roles of antigens and antibodies within the structure of immune complexes are reversed, so that a single monoclonal antibody, rather than polyclonal sera or expensive mAb cocktails can be used. We tested this approach in the context of Mycobacterium tuberculosis (MTB) infection by linking the highly immunogenic and potentially protective Ag85B with the oligomeric Acr (alpha crystallin, HspX) antigen. When combined with an anti-Acr monoclonal antibody, the fusion protein formed ICM which bound to C1q component of the complement system and were readily taken up by antigen-presenting cells in vitro. ICM induced a strong Th1/Th2 mixed type antibody response, which was comparable to cholera toxin adjuvanted antigen, but only moderate levels of T cell proliferation and IFN-γ secretion. Unfortunately, the systemic administration of ICM did not confer statistically significant protection against intranasal MTB challenge, although a small BCG-boosting effect was observed. We conclude that ICM are capable of inducing strong humoral responses to incorporated antigens and may be a suitable vaccination approach for pathogens other than MTB, where antibody-based immunity may play a more protective role

The impact of point mutations in the human androgen receptor : classification of mutations on the basis of transcriptional activity

Peer reviewedPublisher PD

A primary care, multi-disciplinary disease management program for opioid-treated patients with chronic non-cancer pain and a high burden of psychiatric comorbidity

BACKGROUND: Chronic non-cancer pain is a common problem that is often accompanied by psychiatric comorbidity and disability. The effectiveness of a multi-disciplinary pain management program was tested in a 3 month before and after trial. METHODS: Providers in an academic general medicine clinic referred patients with chronic non-cancer pain for participation in a program that combined the skills of internists, clinical pharmacists, and a psychiatrist. Patients were either receiving opioids or being considered for opioid therapy. The intervention consisted of structured clinical assessments, monthly follow-up, pain contracts, medication titration, and psychiatric consultation. Pain, mood, and function were assessed at baseline and 3 months using the Brief Pain Inventory (BPI), the Center for Epidemiological Studies-Depression Scale scale (CESD) and the Pain Disability Index (PDI). Patients were monitored for substance misuse. RESULTS: Eighty-five patients were enrolled. Mean age was 51 years, 60% were male, 78% were Caucasian, and 93% were receiving opioids. Baseline average pain was 6.5 on an 11 point scale. The average CESD score was 24.0, and the mean PDI score was 47.0. Sixty-three patients (73%) completed 3 month follow-up. Fifteen withdrew from the program after identification of substance misuse. Among those completing 3 month follow-up, the average pain score improved to 5.5 (p = 0.003). The mean PDI score improved to 39.3 (p < 0.001). Mean CESD score was reduced to 18.0 (p < 0.001), and the proportion of depressed patients fell from 79% to 54% (p = 0.003). Substance misuse was identified in 27 patients (32%). CONCLUSIONS: A primary care disease management program improved pain, depression, and disability scores over three months in a cohort of opioid-treated patients with chronic non-cancer pain. Substance misuse and depression were common, and many patients who had substance misuse identified left the program when they were no longer prescribed opioids. Effective care of patients with chronic pain should include rigorous assessment and treatment of these comorbid disorders and intensive efforts to insure follow up

Proteomic Comparison of Entamoeba histolytica and Entamoeba dispar and the Role of E. histolytica Alcohol Dehydrogenase 3 in Virulence

The protozoan intestinal parasite Entamoeba histolytica infects millions of people worldwide and is capable of causing amebic dysentery and amebic liver abscess. The closely related species Entamoeba dispar colonizes many more individuals, but this organism does not induce disease. To identify molecular differences between these two organisms that may account for their differential ability to cause disease in humans, we used two-dimensional gel-based (DIGE) proteomic analysis to compare whole cell lysates of E. histolytica and E. dispar. We observed 141 spots expressed at a substantially (>5-fold) higher level in E. histolytica HM-1∶IMSS than E. dispar and 189 spots showing the opposite pattern. Strikingly, 3 of 4 proteins consistently identified as different at a greater than 5-fold level between E. histolytica HM-1∶IMSS and E. dispar were identical to proteins recently identified as differentially expressed between E. histolytica HM-1∶IMSS and the reduced virulence strain E. histolytica Rahman. One of these was E. histolytica alcohol dehydrogenase 3 (EhADH3). We found that E. histolytica possesses a higher level of NADP-dependent alcohol dehydrogenase activity than E. dispar and that some EhADH3 can be localized to the surface of E. histolytica. Episomal overexpression of EhADH3 in E. histolytica trophozoites resulted in only subtle phenotypic differences in E. histolytica virulence in animal models of amebic colitis and amebic liver abscess, making it difficult to directly link EhADH3 levels to virulence differences between E. histolytica and less-pathogenic Entamoeba

Robust Bounds on Choosing from Large Tournaments

Tournament solutions provide methods for selecting the "best" alternatives from a tournament and have found applications in a wide range of areas. Previous work has shown that several well-known tournament solutions almost never rule out any alternative in large random tournaments. Nevertheless, all analytical results thus far have assumed a rigid probabilistic model, in which either a tournament is chosen uniformly at random, or there is a linear order of alternatives and the orientation of all edges in the tournament is chosen with the same probabilities according to the linear order. In this work, we consider a significantly more general model where the orientation of different edges can be chosen with different probabilities. We show that a number of common tournament solutions, including the top cycle and the uncovered set, are still unlikely to rule out any alternative under this model. This corresponds to natural graph-theoretic conditions such as irreducibility of the tournament. In addition, we provide tight asymptotic bounds on the boundary of the probability range for which the tournament solutions select all alternatives with high probability.Comment: Appears in the 14th Conference on Web and Internet Economics (WINE), 201

A mobile phone application for the assessment and management of youth mental health problems in primary care: a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Over 75% of mental health problems begin in adolescence and primary care has been identified as the target setting for mental health intervention by the World Health Organisation. The <it>mobiletype </it>program is a mental health assessment and management mobile phone application which monitors mood, stress, coping strategies, activities, eating, sleeping, exercise patterns, and alcohol and cannabis use at least daily, and transmits this information to general practitioners (GPs) via a secure website in summary format for medical review.</p> <p>Methods</p> <p>We conducted a randomised controlled trial in primary care to examine the mental health benefits of the <it>mobiletype </it>program. Patients aged 14 to 24 years were recruited from rural and metropolitan general practices. GPs identified and referred eligible participants (those with mild or more mental health concerns) who were randomly assigned to either the intervention group (where mood, stress, and daily activities were monitored) or the attention comparison group (where only daily activities were monitored). Both groups self-monitored for 2 to 4 weeks and reviewed the monitoring data with their GP. GPs, participants, and researchers were blind to group allocation at randomisation. Participants completed pre-, post-, and 6-week post-test measures of the Depression, Anxiety, Stress Scale and an Emotional Self Awareness (ESA) Scale.</p> <p>Results</p> <p>Of the 163 participants assessed for eligibility, 118 were randomised and 114 participants were included in analyses (intervention group n = 68, comparison group n = 46). Mixed model analyses revealed a significant group by time interaction on ESA with a medium size of effect suggesting that the <it>mobiletype </it>program significantly increases ESA compared to an attention comparison. There was no significant group by time interaction for depression, anxiety, or stress, but a medium to large significant main effect for time for each of these mental health measures. Post-hoc analyses suggested that participation in the RCT lead to enhanced GP mental health care at pre-test and improved mental health outcomes.</p> <p>Conclusions</p> <p>Monitoring mental health symptoms appears to increase ESA and implementing a mental health program in primary care and providing frequent reminders, clinical resources, and support to GPs substantially improved mental health outcomes for the sample as a whole.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00794222">NCT00794222</a>.</p