A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Rapid Changes in the Light/Dark Cycle Disrupt Memory of Conditioned Fear in Mice

Background: Circadian rhythms govern many aspects of physiology and behavior including cognitive processes. Components of neural circuits involved in learning and memory, e.g., the amygdala and the hippocampus, exhibit circadian rhythms in gene expression and signaling pathways. The functional significance of these rhythms is still not understood. In the present study, we sought to determine the impact of transiently disrupting the circadian system by shifting the light/ dark (LD) cycle. Such ‘‘jet lag’ ’ treatments alter daily rhythms of gene expression that underlie circadian oscillations as well as disrupt the synchrony between the multiple oscillators found within the body. Methodology/Principal Findings: We subjected adult male C57Bl/6 mice to a contextual fear conditioning protocol either before or after acute phase shifts of the LD cycle. As part of this study, we examined the impact of phase advances and phase delays, and the effects of different magnitudes of phase shifts. Under all conditions tested, we found that recall of fear conditioned behavior was specifically affected by the jet lag. We found that phase shifts potentiated the stress-evoked corticosterone response without altering baseline levels of this hormone. The jet lag treatment did not result in overall sleep deprivation, but altered the temporal distribution of sleep. Finally, we found that prior experience of jet lag helps to compensate for the reduced recall due to acute phase shifts. Conclusions/Significance: Acute changes to the LD cycle affect the recall of fear-conditioned behavior. This suggests that

Predictors of mortality in HIV-associated hospitalizations in Portugal: a hierarchical survival model

<p>Abstract</p> <p>Background</p> <p>The beneficial effects of highly active antiretroviral therapy, increasing survival and the prevention of AIDS defining illness development are well established. However, the annual Portuguese hospital mortality is still higher than expected. It is crucial to understand the hospitalization behaviour to better allocate resources. This study investigates the predictors of mortality in HIV associated hospitalizations in Portugal through a hierarchical survival model.</p> <p>Methods</p> <p>The study population consists of 12,078 adult discharges from patients with HIV infection diagnosis attended at Portuguese hospitals from 2005–2007 that were registered on the diagnosis-related groups' database.</p> <p>We used discharge and hospital level variables to develop a hierarchical model. The discharge level variables were: age, gender, type of admission, type of diagnoses-related group, related HIV complication, the region of the patient's residence, the number of diagnoses and procedures, the Euclidean distance from hospital to the centroid of the patient's ward, and if patient lived in the hospital's catchment area. The hospital characteristics include size and hospital classification according to the National Health System. Kaplan-Meier plots were used to examine differences in survival curves. Cox proportional hazard models with frailty were applied to identify independent predictors of hospital mortality and to calculate hazard ratios (HR).</p> <p>Results</p> <p>The Cox proportional model with frailty showed that male gender, older patient, great number of diagnoses and pneumonia increased the hazard of HIV related hospital mortality. On the other hand tuberculosis was associated with a reduced risk of death. Central hospital discharge also presents less risk of mortality.</p> <p>The frailty variance was small but statistically significant, indicating hazard ratio heterogeneity among hospitals that varied between 0.67 and 1.34, and resulted in two hospitals with HR different from the average risk.</p> <p>Conclusion</p> <p>The frailty model suggests that there are unmeasured factors affecting mortality in HIV associated hospitalizations. Consequently, for healthcare policy purposes, hospitals should not all be treated in an equal manner.</p

Modulation of Mouse Coagulation Gene Transcription following Acute In Vivo Delivery of Synthetic Small Interfering RNAs Targeting HNF4α and C/EBPα

Hepatocyte nuclear factor 4α (HNF4α) and CCAAT/enhancer-binding protein α (C/EBPα) are important for the transcriptional control of coagulation factors. To determine in vivo the direct role of HNF4α and C/EBPα in control of genes encoding coagulation factors, a synthetic small interfering (si)RNA approach was used that enabled strong reduction of mouse hepatic HNF4α and C/EBPα under conditions that minimized target-related secondary effects. For both HNF4α and C/EBPα, intravenous injection of specific synthetic siRNAs (siHNF4α and siC/EBPα) resulted in more than 75% reduction in their liver transcript and protein levels 2 days post-injection. For siHNF4α, this coincided with marked and significantly reduced transcript levels of the coagulation genes Hrg, Proz, Serpina5, F11, F12, F13b, Serpinf2, F5, and F9 (in order of magnitude of effect) as compared to levels in control siRNA injected animals. Significant decreases in HNF4α target gene mRNA levels were also observed at 5 days post-siRNA injection, despite a limited level of HNF4α knockdown at this time point. Compared to HNF4α, C/EBPα knockdown had a modest impact on genes encoding coagulation factors. A strong reduction in C/EBPα transcript and protein levels resulted in significantly affected transcript levels of the control genes Pck1 and Fasn and a modest downregulation for coagulation genes Fba, Fbg and F5. F5 and F11 were the sole coagulation genes that were significantly affected upon prolonged (5 day) C/EBPα knockdown. We conclude that in the mouse, HNF4α has a direct and essential regulatory role for multiple hepatic coagulation genes, while a role for C/EBPα is more restricted. In addition, this study demonstrates that synthetic siRNA provides a simple and fast means for determining liver transcription factor involvement in vivo

Mammalian BTBD12 (SLX4) Protects against Genomic Instability during Mammalian Spermatogenesis

The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations of human BTBD12 have been reported in a new sub-type of Fanconi anemia patients. Recent studies have implicated the fly and worm orthologs, MUS312 and HIM-18, in the regulation of meiotic crossovers arising from double-strand break (DSB) initiating events and also in genome stability prior to meiosis. Using a Btbd12 mutant mouse, we analyzed the role of BTBD12 in mammalian gametogenesis. BTBD12 localizes to pre-meiotic spermatogonia and to meiotic spermatocytes in wildtype males. Btbd12 mutant mice have less than 15% normal spermatozoa and are subfertile. Loss of BTBD12 during embryogenesis results in impaired primordial germ cell proliferation and increased apoptosis, which reduces the spermatogonial pool in the early postnatal testis. During prophase I, DSBs initiate normally in Btbd12 mutant animals. However, DSB repair is delayed or impeded, resulting in persistent γH2AX and RAD51, and the choice of repair pathway may be altered, resulting in elevated MLH1/MLH3 focus numbers at pachynema. The result is an increase in apoptosis through prophase I and beyond. Unlike yeast Slx4, therefore, BTBD12 appears to function in meiotic prophase I, possibly during the recombination events that lead to the production of crossovers. In line with its expected regulation by ATM kinase, BTBD12 protein is reduced in the testis of Atm−/− males, and Btbd12 mutant mice exhibit increased genomic instability in the form of elevated blood cell micronucleus formation similar to that seen in Atm−/− males. Taken together, these data indicate that BTBD12 functions throughout gametogenesis to maintain genome stability, possibly by co-ordinating repair processes and/or by linking DNA repair events to the cell cycle via ATM

Complementary therapy use by patients and parents of children with asthma and the implications for NHS care: a qualitative study

BACKGROUND: Patients are increasingly using complementary therapies, often for chronic conditions. Asthma is the most common chronic condition in the UK. Previous research indicates that some asthma patients experience gaps in their NHS care. However, little attention has been given to how and why patients and parents of children with asthma use complementary therapies and the implications for NHS care. METHODS: Qualitative study, comprising 50 semi-structured interviews with a purposeful sample of 22 adults and 28 children with asthma (plus a parent), recruited from a range of NHS and non-NHS settings in Bristol, England. Data analysis was thematic, drawing on the principles of constant comparison. RESULTS: A range of complementary therapies were being used for asthma, most commonly Buteyko breathing and homeopathy. Most use took place outside of the NHS, comprising either self-treatment or consultation with private complementary therapists. Complementary therapies were usually used alongside not instead of conventional asthma treatment. A spectrum of complementary therapy users emerged, including "committed", "pragmatic" and "last resort" users. Motivating factors for complementary therapy use included concerns about conventional NHS care ("push factors") and attractive aspects of complementary therapies ("pull factors"). While participants were often uncertain whether therapies had directly helped their asthma, breathing techniques such as the Buteyko Method were most notably reported to enhance symptom control and enable reduction in medication. Across the range of therapies, the process of seeking and using complementary therapies seemed to help patients in two broad ways: it empowered them to take greater personal control over their condition rather than feel dependant on medication, and enabled exploration of a broader range of possible causes of their asthma than commonly discussed within NHS settings. CONCLUSION: Complementary therapy use reflects patients' and parents' underlying desire for greater self-care and need of opportunities to address some of their concerns regarding NHS asthma care. Self-management of chronic conditions is increasingly promoted within the NHS but with little attention to complementary therapy use as one strategy being used by patients and parents. With their desire for self-help, complementary therapy users are in many ways adopting the healthcare personas that current policies aim to encourage

Using and Reporting the Delphi Method for Selecting Healthcare Quality Indicators: A Systematic Review

OBJECTIVE: Delphi technique is a structured process commonly used to developed healthcare quality indicators, but there is a little recommendation for researchers who wish to use it. This study aimed 1) to describe reporting of the Delphi method to develop quality indicators, 2) to discuss specific methodological skills for quality indicators selection 3) to give guidance about this practice. METHODOLOGY AND MAIN FINDING: Three electronic data bases were searched over a 30 years period (1978-2009). All articles that used the Delphi method to select quality indicators were identified. A standardized data extraction form was developed. Four domains (questionnaire preparation, expert panel, progress of the survey and Delphi results) were assessed. Of 80 included studies, quality of reporting varied significantly between items (9% for year's number of experience of the experts to 98% for the type of Delphi used). Reporting of methodological aspects needed to evaluate the reliability of the survey was insufficient: only 39% (31/80) of studies reported response rates for all rounds, 60% (48/80) that feedback was given between rounds, 77% (62/80) the method used to achieve consensus and 57% (48/80) listed quality indicators selected at the end of the survey. A modified Delphi procedure was used in 49/78 (63%) with a physical meeting of the panel members, usually between Delphi rounds. Median number of panel members was 17(Q1:11; Q3:31). In 40/70 (57%) studies, the panel included multiple stakeholders, who were healthcare professionals in 95% (38/40) of cases. Among 75 studies describing criteria to select quality indicators, 28 (37%) used validity and 17(23%) feasibility. CONCLUSION: The use and reporting of the Delphi method for quality indicators selection need to be improved. We provide some guidance to the investigators to improve the using and reporting of the method in future surveys

Sentencing drug offenders under the 2003 Criminal Justice Act: Challenges for the probation service

For the most part the 2003 Criminal Justice Act, which came into effect in England and Wales in April 2005, was accepted by the probation service with relatively little opposition. Given the enormity of its impact acquiescence to this degree of change ought to come as something of a surprise. The 2003 Act changed fundamentally the nature of community supervision, it brought to an end the traditional range of non-custodial penalties and replaced them with a single community order to which sentencers could add any of 12 possible requirements. This paper considers the impact of the 2003 legislation on one particular offender group - drug misusers. Drug misusing offenders have the potential to pose serious difficulties for probation officers; the habitual nature of drug addiction and a tendency toward an irregular lifestyle make drug misusers particularly susceptible to breach. Under the new legislation courts have significantly fewer options available to them when responding to incidents of offender non-compliance. This paper argues that many of the provisions of the 2003 Act together with developments elsewhere in the UK are likely to have impacted disproportionately on those groups whose lifestyles are chaotic and whose routines are incompatible with the terms and conditions of modern day probation practice. It concludes that greater flexibility towards non-compliance, supported by regular and consistent judicial review, would encourage improved rates of compliance and retention in treatment and improved outcomes for offenders

Interplay between Synaptonemal Complex, Homologous Recombination, and Centromeres during Mammalian Meiosis

The intimate synapsis of homologous chromosome pairs (homologs) by synaptonemal complexes (SCs) is an essential feature of meiosis. In many organisms, synapsis and homologous recombination are interdependent: recombination promotes SC formation and SCs are required for crossing-over. Moreover, several studies indicate that initiation of SC assembly occurs at sites where crossovers will subsequently form. However, recent analyses in budding yeast and fruit fly imply a special role for centromeres in the initiation of SC formation. In addition, in budding yeast, persistent SC–dependent centromere-association facilitates the disjunction of chromosomes that have failed to become connected by crossovers. Here, we examine the interplay between SCs, recombination, and centromeres in a mammal. In mouse spermatocytes, centromeres do not serve as SC initiation sites and are invariably the last regions to synapse. However, centromeres are refractory to de-synapsis during diplonema and remain associated by short SC fragments. Since SC–dependent centromere association is lost before diakinesis, a direct role in homolog segregation seems unlikely. However, post–SC disassembly, we find evidence of inter-centromeric connections that could play a more direct role in promoting homolog biorientation and disjunction. A second class of persistent SC fragments is shown to be crossover-dependent. Super-resolution structured-illumination microscopy (SIM) reveals that these structures initially connect separate homolog axes and progressively diminish as chiasmata form. Thus, DNA crossing-over (which occurs during pachynema) and axis remodeling appear to be temporally distinct aspects of chiasma formation. SIM analysis of the synapsis and crossover-defective mutant Sycp1−/− implies that SCs prevent unregulated fusion of homolog axes. We propose that SC fragments retained during diplonema stabilize nascent bivalents and help orchestrate local chromosome reorganization that promotes centromere and chiasma function

Oxamniquine resistance alleles are widespread in Old World Schistosoma mansoni and predate drug deployment

Do mutations required for adaptation occur de novo, or are they segregating within populations as standing genetic variation? This question is key to understanding adaptive change in nature, and has important practical consequences for the evolution of drug resistance. We provide evidence that alleles conferring resistance to oxamniquine (OXA), an antischistosomal drug, are widespread in natural parasite populations under minimal drug pressure and predate OXA deployment. OXA has been used since the 1970s to treat Schistosoma mansoni infections in the New World where S. mansoni established during the slave trade. Recessive loss-of-function mutations within a parasite sulfotransferase (SmSULT-OR) underlie resistance, and several verified resistance mutations, including a deletion (p.E142del), have been identified in the New World. Here we investigate sequence variation in SmSULT-OR in S. mansoni from the Old World, where OXA has seen minimal usage. We sequenced exomes of 204 S. mansoni parasites from West Africa, East Africa and the Middle East, and scored variants in SmSULT-OR and flanking regions. We identified 39 non-synonymous SNPs, 4 deletions, 1 duplication and 1 premature stop codon in the SmSULT-OR coding sequence, including one confirmed resistance deletion (p.E142del). We expressed recombinant proteins and used an in vitro OXA activation assay to functionally validate the OXA-resistance phenotype for four predicted OXA-resistance mutations. Three aspects of the data are of particular interest: (i) segregating OXA-resistance alleles are widespread in Old World populations (4.29–14.91% frequency), despite minimal OXA usage, (ii) two OXA-resistance mutations (p.W120R, p.N171IfsX28) are particularly common (>5%) in East African and Middle-Eastern populations, (iii) the p.E142del allele has identical flanking SNPs in both West Africa and Puerto Rico, suggesting that parasites bearing this allele colonized the New World during the slave trade and therefore predate OXA deployment. We conclude that standing variation for OXA resistance is widespread in S. mansoni