Conditionally-live attenuated SIV upregulates global T effector memory cell frequency under replication permissive conditions.

Background: Live attenuated SIV induces potent protection against superinfection with virulent virus; however the mechanism of this vaccine effect is poorly understood. Such knowledge is important for the development of clinically acceptable vaccine modalities against HIV. Results: Using a novel, doxycycline dependent, replication-competent live-attenuated SIVmac239Δnef (SIVrtTAΔnef), we show that under replication-permissive conditions SIV-rtTAΔnef is fully viable. Twelve rhesus macaques were infected with a peak plasma vRNA on average two log10 lower than in 6 macaques infected with unconditionally replication-competent SIVΔnef. Consistent with the attenuated phenotype of the viruses the majority of animals displayed low or undetectable levels of viraemia by 42-84 days after infection. Next, comparison of circulating T cells before and after chronic infection with parental SIVΔnef revealed a profound global polarisation toward CD28-CCR7- T-effector memory 2 (TEM2) cells within CD95+CD4+ and CD95+CD8+ populations. Critically, a similar effect was seen in the CD95+ CD4+ population and to somewhat lesser extent in the CD95+ CD8+ population of SIV-rtTAΔnef chronically infected macaques that were maintained on doxycycline, but was not seen in animals from which doxycycline had been withdrawn. The proportions of gut-homing T-central memory (TCM) and TEM defined by the expression of α4β7 and CD95 and differential expression of CD28 were increased in CD4 and CD8 cells under replication competent conditions and gut-homing CD4 TCM were also significantly increased under non-permissive conditions. TEM2 polarisation was seen in the small intestines of animals under replication permissive conditions but the effect was less pronounced than in the circulation. Intracellular cytokine staining of circulating SIV-specific T cells for IL-2, IFN-γ, TNF-α and IL-17 showed that the extent of polyfunctionality in CD4 and CD8 T cells was associated with replication permissivity; however, signature patterns of cytokine combinations were not distinguishable between groups of macaques. Conclusion: Taken together our results show that the global T memory cell compartment is profoundly skewed towards a mature effector phenotype by attenuated SIV. Results with the replication-conditional mutant suggest that maintenance of this effect, that may be important in vaccine design, might require persistence of replicating virus

Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated

The emerging "standard of reasonableness" for search and seizure in American public schools : pre and post-New Jersey v. T.L.O.

Search and seizure involving public school children is a relatively recent issue in American public education. Prior to 1985 search situations were litigated in virtually every level of state and federal court except the United States Supreme Court. In December 1985, the Supreme Court decided New Jersey v. T.L.O. The crux of this decision was the annunciation of "reasonable suspicion" as the standard to which school officials would be held. The Court established an inquiry process to assist in determining the legality of a search, but did not define "reasonableness.

Home school curricula : constitutional issues

The purpose of this study was to analyze the extent to which state statutes offer some regulation of the curricula offered in home schooling situations. A further purpose was to analyze court decisions which have had some impact on the curricula of home schools. The analysis of statutes showed that all fifty states have provisions which allow home schooling. Twenty-three states have passed laws specifically related to home schooling. Eighteen states allow home schooling by approval of a governmental agency or body. Home schooling is allowed in two states by case law and in one state by Attorney General's ruling. The remaining six states have statutes that allow home schooling by either licensure or registration as a private religious school or "other acceptable means of education.

A program of extensive research in current methods and problems and future trends in an orientation program in physical education for the college freshman : culminating in an orientation manual including the philosophical, educational, physical and recreational aspects of physical education

Have you asked yourself why you came to college? Has it because Mother and Dad wanted you to? Or because the rest of the crowd was going? Was it because you yourself want to be a more significant person, to live a more richly abundant life? Was it to gain that intellectual and social maturity which makes a professional course more effective or a private life more significant? Modern education demands that a college education should comprise training not only of the mind but of all the capabilities of the individual. A college student may have A's in history and chemistry, but if she has a slouching figure and clumsy movements, if she is a wall flower at a dance and a failure at a swimming party is she your ideal of a college-educated woman? And so physical education offers you an opportunity for acquiring knowledge, skills, and attitudes and values which contribute to complete living now and in the future. Physical education is a phase of total education, and as such aims toward the same goal - that of orienting the individual in the process of meeting the persistent problems of living. Therefore, satisfactory fulfillment of the physical education requirement is necessary for a degree

Still-life drawing and figure drawing

This thesis consists of still-life drawings and figure drawings. The drawings consist of lines of different intensities and lengths which define interior space as well as exterior space, without the use of crosshatching or other shading devices. The drawings are kept on a rather small scale so that more spontaneity and line control are possible. Most of the flowers used for the drawings were in a dry or wilted condition which gave greater angularity. Sunflowers were well suited to this drawing technique in that the surfaces have so much contrast. The leaves, stems and calyx were sharp and irregular, which contrasted with the geometric conformation of the seeds. Concise lines were also used in the figure drawings in order to show the movement of the muscles around the body rather than depicting the figures as simple contour lines and shading. The lines of different intensities helped to project the muscle structure of the body more successfully than simply shading the figures might have. Much consideration was given to the depth and proportion of the works as well as the conformation of the figures. Although many of the drawings are studies of the figure only, some of the figures were placed in an environment which gives an added dimension to the work and the relationship of the figure to the objects surrounding it

Equilibrium configurations of two charged masses in General Relativity

An asymptotically flat static solution of Einstein-Maxwell equations which describes the field of two non-extreme Reissner - Nordstr\"om sources in equilibrium is presented. It is expressed in terms of physical parameters of the sources (their masses, charges and separating distance). Very simple analytical forms were found for the solution as well as for the equilibrium condition which guarantees the absence of any struts on the symmetry axis. This condition shows that the equilibrium is not possible for two black holes or for two naked singularities. However, in the case when one of the sources is a black hole and another one is a naked singularity, the equilibrium is possible at some distance separating the sources. It is interesting that for appropriately chosen parameters even a Schwarzschild black hole together with a naked singularity can be "suspended" freely in the superposition of their fields.Comment: 4 pages; accepted for publication in Phys. Rev.

True Colors: Police Officers and Rape Myth Acceptance

Institutionally, significant advancements in rape law reform have occurred. Culturally, police officers sometimes fail to adopt these changes. A survey designed to assess acceptance of rape myths was administered to 891 police officers in two southeastern states. The study found that the majority of police officers view the overall crime of rape as a serious one, however, approximately 6% provided sexist feedback that supports rape myths. These findings indicate that more work is needed in altering the attitudes of police officers

North Carolina Sexual Offender Legislation: Policy Placebo?

Current legislation at the state and federal level is largely based on the premise that we can best protect children by prohibiting sexual offenders’ access to children through the use of residency restrictions, employment sanctions, and community notification. While well intentioned, these policies are short sighted and based more on public misperceptions than empirical research. In this study, the authors assess sexual offenders’ perceptions of residency restrictions in the state of North Carolina. The study population was comprised of a nonrandom sample of 231 adult sexual offenders from 11 outpatient sexual offender treatment sites in North Carolina. The majority (151) of sexual offenders stated that housing restrictions do nothing to prevent them from reoffending. More than half (135) indicated that no residency restrictions would serve as an effective deterrent. These findings indicate the need for a more comprehensive approach to the community management of sexual offenders

Behind the Blue Line: Investigating Police Officers’ Attitudes toward Rape

The current study contributes to what is known about police officers’ attitudes toward rape. A survey was administered to 891 sworn police officers in two states in the southeastern United States. The surveys were designed to assess police officers’ acceptance of rape myths. It was hypothesized that police officers would be accepting of rape myths, which are inherently misogynistic. Attitudes toward rape were expected to vary according to educational attainment and experience with rape investigations, such that higher levels of education and more experience with rape investigations would lead to the rejection of rape myths. There was a significant difference in the acceptance of rape myths with varying levels of educational attainment and experience with rape investigations