Inhaled PYY(3–36) dry-powder formulation for appetite suppression

Objective: Peptide YY3–36 [PYY(3–36)] has shown efficacy in appetite suppression when dosed by injection modalities (intraperitoneal (IP)/subcutaneous). Transitioning to needle-free delivery, towards inhalation, often utilizes systemic pharmacokinetics as a key endpoint to compare different delivery methods and doses. Systemic pharmacokinetics were evaluated for PYY3–36 when delivered by IP, subcutaneous, and inhalation, the systemic pharmacokinetics were then used to select doses in an appetite suppression pharmacodynamic study.

Methods: Dry-powder formulations were manufactured by spray drying and delivered to mice via nose only inhalation. The systemic plasma, lung tissue, and bronchoalveolar lavage fluid pharmacokinetics of different inhalation doses of PYY(3–36) were compared to IP and subcutaneous efficacious doses. Based on these pharmacokinetic data, inhalation doses of 70:30 PYY(3–36):Dextran T10 were evaluated in a mouse model of appetite suppression and compared to IP and subcutaneous data.

Results: Inhalation pharmacokinetic studies showed that plasma exposure was similar for a 2?×?higher inhalation dose when compared to subcutaneous and IP delivery. Inhalation doses of 0.22 and 0.65?mg/kg were for efficacy studies. The results showed a dose-dependent (not dose proportional) decrease in food consumption over 4?h, which is similar to IP and subcutaneous delivery routes.

Conclusions: The pharmacokinetic and pharmacodynamics results substantiate the ability of pharmacokinetic data to inform pharmacodynamics dose selection for inhalation delivery of the peptide PYY(3–36). Additionally, engineered PYY(3–36):Dextran T10 particles delivered to the respiratory tract show promise as a non-invasive therapeutic for appetite suppression.     

Reduced specificity of autobiographical memory in Cluster C personality disorders and the role of depression, worry, and experiential avoidance.

The study objective was to investigate whether, compared with nonclinical controls, participants with an avoidant, dependent, or obsessive–compulsive Cluster C personality disorder (PD) manifested reduced levels of memory specificity and whether the association of Cluster C PDs with memory specificity is mediated by repetitive negative thoughts and experiential avoidance. The Autobiographical Memory Test (R. J. McNally, N. B. Lasko, M. L. Macklin, & R. K. Pitman, 1995) was administered along with self-report measures (translated into Dutch) for repetitive, uncontrollable, and negative thinking in the form of worry (Penn State Worry Questionnaire; T. J. Meyer, M. L. Miller, R. L. Metzger, & T. D. Borkovec, 1990) and experiential avoidance (Acceptance and Action Questionnaire; S. C. Hayes et al., 2004) to 294 clinical participants diagnosed with Axis I disorders (assessed with the Structured Clinical Interview for DSM–IV Axis I Disorders [SCID-I]; M. B. First, R. L. Spitzer, M. Gibbon, & J. B. W. Williams, 1994) and Axis II disorders (assessed with the SCID-II; M. B. First, R. L. Spitzer, M. Gibbon, & J. B. W. Williams, 1997)—202 with avoidant, 49 with dependent, and 120 with obsessive–compulsive PD—and to 108 matched nonclinical controls. Participants with a Cluster C PD showed lower levels of memory specificity than did nonclinical controls. Depression and worry mediated the effect of Cluster C PDs on memory specificity. Besides depression severity, repetitive, uncontrollable, and negative thinking may constitute a general mechanism mediating the association of various Axis I and II disorders with memory specificity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Robust Higher Order Potentials for Enforcing Label Consistency

This paper proposes a novel framework for labelling problems which is able to combine multiple segmentations in a principled manner. Our method is based on higher order conditional random fields and uses potentials defined on sets of pixels (image segments) generated using unsupervised segmentation algorithms. These potentials enforce label consistency in image regions and can be seen as a generalization of the commonly used pairwise contrast sensitive smoothness potentials. The higher order potential functions used in our framework take the form of the Robust P ⁿ model and are more general than the P ⁿ Potts model recently proposed by Kohli et al. We prove that the optimal swap and expansion moves for energy functions composed of these potentials can be computed by solving a st-mincut problem. This enables the use of powerful graph cut based move making algorithms for performing inference in the framework. We test our method on the problem of multi-class object segmentation by augmenting the conventional crf used for object segmentation with higher order potentials defined on image regions. Experiments on challenging data sets show that integration of higher order potentials quantitatively and qualitatively improves results leading to much better definition of object boundaries. We believe that this method can be used to yield similar improvements for many other labelling problems.     

Medicare/medicaid billing fraud and abuse by psychologists.

Medicare/Medicaid billing fraud and abuse can be prosecuted under a wider array of laws than apply within the private sector. Cases are typically initiated by whistleblowers or through detection of unusual billing patterns. Few psychologists in independent practice have ever been convicted of Medicare/Medicaid billing fraud or abuse, but government antifraud efforts against psychologists appear to be on the rise. These efforts are pursued under the auspices of containing spiraling health care costs, but they can uncover unintentional billing abuse by psychologists, arising from general ignorance of claim-processing procedures, lack of uniformity across insurance programs, constantly changing guidelines, and ambiguous interpretations. Recent investigations in south Texas have especially targeted the use of extenders for psychological and neuropsychological testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Invention from War: a circumstantial modernism for Australian architecture

Between 1942 and 1945, Australian architects and engineers within the Allied Works Council and the US Army Corps of Engineers undertook a vast programme of building works to assist the campaign to drive Japanese forces northward through the Southwest Pacific and avoid invasion.¹ Huge distances, lack of time and the need to wage a campaign from the air lay behind US General Douglas Macarthur’s phrase that it would be an ‘engineer’s war’. By necessity, buildings such as airfields, hospitals, camps, warehouses, and other structures had to be light weight, constructed quickly, and inevitably dropped in by air as easily handled pre-cut packages. With the lack of American and European softwoods in the Australasian region, an unlikely local material was pressed into war service – unseasoned or ‘green’ Australian hardwood. It was a material choice that would have profound implications for two reasons. First, in the years of conflict, circumstances dictated the unprecedented innovation and experiment in light-weight timber structures. Second, in an echo of Lewis Mumford’s poignant maxim that ‘war is the health of the machine’², the systematisation and ruthless economy inherent in wartime timber buildings would influence the development and practice of a particular form of modern architecture in Australia in the late 1940s and the 1950s.     

Pain, depression, and physical functioning following burn injury.

Objective: Little is known about how pain and depression after burn injury may influence long-term outcomes such as physical functioning. This prospective study examined associations between pain, depression, and physical functioning in a sample of burn injury survivors. Design and Participants: Questionnaires assessing pain, depression, and physical functioning were completed by 64 (52% of original sample) adult burn survivors shortly after discharge from burn care and at 1- and 2-year follow-ups. Results: Pain and physical functioning improved over the 2 years of the study, whereas depression levels were stable. Pain and depression were associated with poorer physical functioning over time, but associations varied according to the time span under consideration. Also, the association between pain and physical functioning was strongest among persons with higher depression scores. Conclusions: Pain and depression may contribute independently to compromises in physical functioning. The co-occurrence of pain and depression represents even greater risk for reduced physical functioning over time among burn survivors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patterns of email use by teachers and implications: A Singapore experience

This paper attempts to identify the patterns of email use by schoolteachers. The findings are based on a survey of 2998 Singapore teachers whose teaching experiences ranged from 24 to 48 months. The result shows that teachers use email mainly to communicate with colleagues, and the degree of email use varies according to the school level that the teachers are working in. While the teachers teaching at higher school levels (Grades 11–12) email their colleagues more frequently than their counterparts teaching at lower school levels especially primary school teachers, the latter tend to email parents more frequently than other teachers. Implications of the findings are discussed in relevance to pre-service teacher education, teacher professional development and ICT adoption in organisations.     

The standard enthalpies of formation of some intermetallic compounds of early 4d and 5d transition metals by high temperature direct synthesis calorimetry

The standard enthalpies of formation of some intermetallic compounds of early 4d and 5d transition metals have been measured by high temperature direct synthesis calorimetry at 1373±2 K. The following results (in kJ/mol of atoms) are reported: ZrMn₂(−24.7±2.7); ZrMo₂(−5.8±5.3); Zr₁₁Os₄(−8.9±2.1); HfCr₂(−4.8±4.3); HfMn₂(−20.3±2.0); HfMo₂(−6.4±4.3); NbRh₃(−21.6±1.8); TaRh₃(−14.0±4.0).