Unravelling the “Black Box”: Treatment-Staff Perceptions of Hermon Prison’s Drug-Rehabilitation Program

This current qualitative study analyzed treatment-staff perceptions of the advantages and weaknesses of Israeli’s primary prison-based drug rehabilitation program, as implemented in Hermon Prison in Israel. Semi-structured interviews were conducted with 12 social workers and recovery mentors who worked as therapists in Hermon Prison during the research period. The analysis showed that the main advantages described were that the program was varied (included psychotherapy, education, vocational training, and work) and required a 1-year stay in a therapeutic community setting, with intensive exposure to eclectic psychotherapy methods and was delivered in a prison that is organizationally and architecturally designed to serve treatment goals. The primary weaknesses that the therapists perceived were shortages of treatment staff (staff turnover was high), individual psychological therapy and of follow-up treatment in the community. The research suggests that reducing these deficiencies may improve the program’s effectiveness, and it offers an initial theoretical model for creating an effective drug rehabilitation program

Asymptotic Expansions for Stationary Distributions of Perturbed Semi-Markov Processes

New algorithms for computing of asymptotic expansions for stationary distributions of nonlinearly perturbed semi-Markov processes are presented. The algorithms are based on special techniques of sequential phase space reduction, which can be applied to processes with asymptotically coupled and uncoupled finite phase spaces.Comment: 83 page

Circumventing antivector immunity: potential use of nonhuman adenoviral vectors

Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

The problem of equilibration and the computation of correlation functions on a quantum computer

We address the question of how a quantum computer can be used to simulate experiments on quantum systems in thermal equilibrium. We present two approaches for the preparation of the equilibrium state on a quantum computer. For both approaches, we show that the output state of the algorithm, after long enough time, is the desired equilibrium. We present a numerical analysis of one of these approaches for small systems. We show how equilibrium (time)-correlation functions can be efficiently estimated on a quantum computer, given a preparation of the equilibrium state. The quantum algorithms that we present are hard to simulate on a classical computer. This indicates that they could provide an exponential speedup over what can be achieved with a classical device.Comment: 25 pages LaTex + 8 figures; various additional comments, results and correction

A new microvertebrate assemblage from the Mussentuchit Member, Cedar Mountain Formation: insights into the paleobiodiversity and paleobiogeography of early Late Cretaceous ecosystems in western North America

The vertebrate fauna of the Late Cretaceous Mussentuchit Member of the Cedar Mountain Formation has been studied for nearly three decades, yet the fossil-rich unit continues to produce new information about life in western North America approximately 97 million years ago. Here we report on the composition of the Cliffs of Insanity (COI) microvertebrate locality, a newly sampled site containing perhaps one of the densest concentrations of microvertebrate fossils yet discovered in the Mussentuchit Member. The COI locality preserves osteichthyan, lissamphibian, testudinatan, mesoeucrocodylian, dinosaurian, metatherian, and trace fossil remains and is among the most taxonomically rich microvertebrate localities in the Mussentuchit Member. To better refine taxonomic identifications of isolated theropod dinosaur teeth, we used quantitative analyses of taxonomically comprehensive databases of theropod tooth measurements, adding new data on theropod tooth morphodiversity in this poorly understood interval. We further provide the first descriptions of tyrannosauroid premaxillary teeth and document the earliest North American record of adocid remains, extending the appearance of this ancestrally Asian clade by 5 million years in western North America and supporting studies of pre-Cenomaninan Laurasian faunal exchange across Beringia. The overabundance of mesoeucrocodylian remains at the COI locality produces a comparatively low measure of relative biodiversity when compared to other microvertebrate sites in the Mussentuchit Member using both raw and subsampling methods. Much more microvertebrate research is necessary to understand the roles of changing ecology and taphonomy that may be linked to transgression of the Western Interior Seaway or microhabitat variation

Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

Disease and treatment-related burden in patients with acromegaly who are biochemically controlled on injectable somatostatin receptor ligands

Medical treatment for acromegaly commonly involves receiving intramuscular or deep subcutaneous injections of somatostatin receptor ligands (SRLs) in most patients. In addition to side effects of treatment, acromegaly patients often still experience disease symptoms even when therapy is successful in controlling GH and IGF-1 levels. Symptoms and side effects can negatively impact patients' health-related quality of life. In this study, we examine the disease- and treatment-related burden associated with SRL injections as reported through the use of the Acromegaly Treatment Satisfaction Questionnaire (Acro-TSQ(C)) and clinician-reported symptom severity through the Acromegaly Index of Severity (AIS). Patients included in this analysis were enrolled in a randomized phase 3 study, were biochemically-controlled (an IGF-1 = 6 months with a stable dose of either long- acting octreotide or lanreotide monotherapy for >= 4 months. The sample (N = 91) was 65% female, 91% Caucasian, with a mean [standard deviation (SD)] age of 53 (1) years. Two-thirds of patients reported that they still experience acromegaly symptoms; 82% of these said they experience symptoms all of the time. Three-fourths experienced gastrointestinal (GI) side effects after injections, and 77% experienced treatment-related injection site reactions (ISRs). Patients commonly reported that these interfered with their daily life, leisure, and work activities. Those with higher symptom severity, as measured by the AIS, scored significantly worse on several Acro-TSQ domains: Symptom Interference, GI Interference, Treatment Satisfaction, and Emotional Reaction. Despite being biochemically controlled with injectable SRLs, most patients reported experiencing acromegaly symptoms that interfere with daily life, leisure, and work. GI side effects and ISRs were also common. This study highlights the significant disease burden that still persists for patients with acromegaly that have achieved biochemical control with the use of injectable SRLs.Diabetes mellitus: pathophysiological changes and therap