Near-optimal mean value estimates for multidimensional Weyl sums

We obtain sharp estimates for multidimensional generalisations of Vinogradov's mean value theorem for arbitrary translation-dilation invariant systems, achieving constraints on the number of variables approaching those conjectured to be the best possible. Several applications of our bounds are discussed

Interprofessional training for final year healthcare students: a mixed methods evaluation of the impact on ward staff and students of a two-week placement and of factors affecting sustainability

BACKGROUND: Multiple care failings in hospitals have led to calls for increased interprofessional training in medical education to improve multi-disciplinary teamwork. Providing practical interprofessional training has many challenges and remains uncommon in medical schools in the UK. Unlike most previous research, this evaluation of an interprofessional training placement takes a multi-faceted approach focusing not only on the impact on students, but also on clinical staff delivering the training and on outcomes for patients. METHODS: We used mixed methods to examine the impact of a two-week interprofessional training placement undertaken on a medical rehabilitation ward by three cohorts of final year medical, nursing and therapy students. We determined the effects on staff, ward functioning and participating students. Impact on staff was evaluated using the Questionnaire for Psychological and Social factors at work (QPSNordic) and focus groups. Ward functioning was inferred from standard measures of care including length of stay, complaints, and adverse events. Impact on students was evaluated using the Readiness for Interprofessional Learning Survey (RIPLS) among all students plus a placement survey among medical students. RESULTS: Between 2007 and 2010, 362 medical students and 26 nursing and therapy students completed placements working alongside the ward staff to deliver patient care. Staff identified benefits including skills recognition and expertise sharing. Ward functioning was stable. Students showed significant improvements in the RIPLS measures of Teamwork, Professional Identity and Patient-Centred Care. Despite small numbers of students from other professions, medical students’ rated the placement highly. Increasing student numbers and budgetary constraints led to the cessation of the placement after three years. CONCLUSIONS: Interprofessional training placements can be delivered in a clinical setting without detriment to care and with benefits for all participants. While financial support is a necessity, it appears that having students from multiple professions is not critical for a valuable training experience; staff from different professions and students from a single profession can work successfully together. Difficulty in aligning the schedules of different student professions is commonly cited as a barrier to interprofessional training. Our experience challenges this and should encourage provision of authentic interprofessional training experience

Impact of translational error-induced and error-free misfolding on the rate of protein evolution

Theoretical calculations suggest that, in addition to translational error-induced protein misfolding, a non-negligible fraction of misfolded proteins are error free.We propose that the anticorrelation between the expression level of a protein and its rate of sequence evolution be explained by an overarching protein-misfolding-avoidance hypothesis that includes selection against both error-induced and error-free protein misfolding, and verify this model by a molecular-level evolutionary simulation.We provide strong empirical evidence for the protein-misfolding-avoidance hypothesis, including a positive correlation between protein expression level and stability, enrichment of misfolding-minimizing codons and amino acids in highly expressed genes, and stronger evolutionary conservation of residues in which nonsynonymous changes are more likely to increase protein misfolding

Are female students in general and nursing students more ready for teamwork and interprofessional collaboration in healthcare?

<p>Abstract</p> <p>Background</p> <p>Interprofessional Education (IPE) is now spreading worldwide and many universities are now including IPE in their curricula. The aim of this study was to investigate whether or not such student characteristics as gender, previous working experience in healthcare, educational progress and features of the learning environment, such as educational programmes and curriculum design, have an impact on their open-mindedness about co-operation with other professions.</p> <p>Methods</p> <p>Medical and nursing students at two Swedish universities were invited to fill in the Readiness for Interprofessional Learning Scale (RIPLS). Totally, 955 students were invited and 70.2% (n = 670) participated in the study. A factor analysis of the RIPLS revealed four item groupings (factors) for our empirical data, but only one had sufficient internal consistency. This factor was labelled "Team Player".</p> <p>Results</p> <p>Regardless of the educational programme, female students were more positive to teamwork than male students. Nursing students in general displayed more positive beliefs about teamwork and collaboration than medical students. Exposure to different interprofessional curricula and previous exposure to interprofessional education were only to a minor extent associated with a positive attitude towards teamwork. Educational progress did not seem to influence these beliefs.</p> <p>Conclusions</p> <p>The establishment of interprofessional teamwork is a major challenge for modern healthcare. This study indicates some directions for more successful interprofessional education. Efforts should be directed at informing particularly male medical students about the need for teamwork in modern healthcare systems. The results also imply that study of other factors, such as the student's personality, is needed for fully understanding readiness for teamwork and interprofessional collaboration in healthcare. We also believe that the RIPL Scale still can be further adjusted.</p

A Genetic Analysis of the Relationship Between Life-history Variation and Heat-shock Tolerance in Drosophila buzzatii

Although exposure to environmental stress is common in most populations, and the physiological effects of stress on individuals are well studied, the evolutionary importance of stress to populations is not well understood. To address multitrait responses to environmental change and potential constraints on character evolution, we analysed, in 100 isofemale lines of Drosophila buzzatii, the genetic relationships between resistance to a short heat shock and several life-history traits: survival in benign conditions, larval developmental time, fecundity and longevity. Estimates of heritability of larval thermotolerance were low, but significant, and all life-history traits varied significantly among isofemale lines. Several of these traits covaried significantly. Most correlations indicated positive life-history relationships, but males and females from lines where female fecundity was higher developed more slowly in the absence of stress, which is a negative life-history relationship. The stress reduced or negated many trait associations, and showed one additional relationship; more larvae from lines that developed fast at 25°C survived to adult after stress than did larvae from slow developing lines. These shifts in fitness relationships, when a single stress bout is applied, suggest that even small increases in environmental stress can have profound effects on evolutionary relationships among life-history traits

Inefficient Quality Control of Thermosensitive Proteins on the Plasma Membrane

BACKGROUND: Misfolded proteins are generally recognised by cellular quality control machinery, which typically results in their ubiquitination and degradation. For soluble cytoplasmic proteins, degradation is mediated by the proteasome. Membrane proteins that fail to fold correctly are subject to ER associated degradation (ERAD), which involves their extraction from the membrane and subsequent proteasome-dependent destruction. Proteins with abnormal transmembrane domains can also be recognised in the Golgi or endosomal system and targeted for destruction in the vacuole/lysosome. It is much less clear what happens to membrane proteins that reach their destination, such as the cell surface, and then suffer damage. METHODOLOGY/PRINCIPAL FINDINGS: We have tested the ability of yeast cells to degrade membrane proteins to which temperature-sensitive cytoplasmic alleles of the Ura3 protein or of phage lambda repressor have been fused. In soluble form, these proteins are rapidly degraded upon temperature shift, in part due to the action of the Doa10 and San1 ubiquitin ligases and the proteasome. When tethered to the ER protein Use1, they are also degraded. However, when tethered to a plasma membrane protein such as Sso1 they escape degradation, either in the vacuole or by the proteasome. CONCLUSIONS/SIGNIFICANCE: Membrane proteins with a misfolded cytoplasmic domain appear not to be efficiently recognised and degraded once they have escaped the ER, even though their defective domains are exposed to the cytoplasm and potentially to cytoplasmic quality controls. Membrane tethering may provide a way to reduce degradation of unstable proteins

Systematic inclusion of mandatory interprofessional education in health professions curricula at Gunma University: a report of student self-assessment in a nine-year implementation

<p>Abstract</p> <p>Background</p> <p>The mandatory interprofessional education programme at Gunma University was initiated in 1999. This paper is a statistical evaluation of the programme from 1999 to 2007.</p> <p>Methods</p> <p>A questionnaire of 10 items to assess the achievement levels of the programme, which was developed independently of other assessment systems published previously, was distributed, as well as two or three open-ended questions to be answered at the end of each annual module. A multivariate analysis of variance model was used, and the factor analysis of the responses was performed with varimax rotation.</p> <p>Results</p> <p>Over all, 1418 respondents of a possible 1629 students completed the survey, for a total response rate of 87.1%. Cronbach's alpha of 10 items was 0.793, revealing high internal consistency. Our original questionnaire was categorized into four subscales as follows: "Role and responsibilities", "Teamwork and collaboration", "Structure and function of training facilities", and "Professional identity". Students in the Department of Occupational Therapy reached a relatively lower level of achievement. In the replies to the open-ended questions, requests for the participation of the medical students were repeated throughout the evaluation period.</p> <p>Conclusion</p> <p>The present four subscales measure "understanding", and may take into account the development of interprofessional education programmes with clinical training in various facilities. The content and quality of clinical training subjects may be remarkably dependent on training facilities, suggesting the importance of full consultation mechanisms in the local network with the relevant educational institutes for medicine, health care and welfare.</p

A four-year, systems-wide intervention promoting interprofessional collaboration

Background: A four-year action research study was conducted across the Australian Capital Territory health system to strengthen interprofessional collaboration (IPC) through multiple intervention activities. Methods: We developed 272 substantial IPC intervention activities involving 2,407 face-to-face encounters with health system personnel. Staff attitudes toward IPC were surveyed yearly using Heinemann et al’s Attitudes toward Health Care Teams and Parsell and Bligh’s Readiness for Interprofessional Learning scales (RIPLS). At study’s end staff assessed whether project goals were achieved. Results: Of the improvement projects, 76 exhibited progress, and 57 made considerable gains in IPC. Educational workshops and feedback sessions were well received and stimulated interprofessional activities. Over time staff scores on Heinemann’s Quality of Interprofessional Care subscale did not change significantly and scores on the Doctor Centrality subscale increased, contrary to predictions. Scores on the RIPLS subscales of Teamwork & Collaboration and Professional Identity did not alter. On average for the assessment items 33% of staff agreed that goals had been achieved, 10% disagreed, and 57% checked ‘neutral’. There was most agreement that the study had resulted in increased sharing of knowledge between professions and improved quality of patient care, and least agreement that between-professional rivalries had lessened and communication and trust between professions improved. Conclusions: Our longitudinal interventional study of IPC involving multiple activities supporting increased IPC achieved many project-specific goals, but improvements in attitudes over time were not demonstrated and neutral assessments predominated, highlighting the difficulties faced by studies targeting change at the systems level and over extended periods

The Mammalian Disaggregase Machinery: Hsp110 Synergizes with Hsp70 and Hsp40 to Catalyze Protein Disaggregation and Reactivation in a Cell-Free System

Bacteria, fungi, protozoa, chromista and plants all harbor homologues of Hsp104, a AAA+ ATPase that collaborates with Hsp70 and Hsp40 to promote protein disaggregation and reactivation. Curiously, however, metazoa do not possess an Hsp104 homologue. Thus, whether animal cells renature large protein aggregates has long remained unclear. Here, it is established that mammalian cytosol prepared from different sources possesses a potent, ATP-dependent protein disaggregase and reactivation activity, which can be accelerated and stimulated by Hsp104. This activity did not require the AAA+ ATPase, p97. Rather, mammalian Hsp110 (Apg-2), Hsp70 (Hsc70 or Hsp70) and Hsp40 (Hdj1) were necessary and sufficient to slowly dissolve large disordered aggregates and recover natively folded protein. This slow disaggregase activity was conserved to yeast Hsp110 (Sse1), Hsp70 (Ssa1) and Hsp40 (Sis1 or Ydj1). Hsp110 must engage substrate, engage Hsp70, promote nucleotide exchange on Hsp70, and hydrolyze ATP to promote disaggregation of disordered aggregates. Similarly, Hsp70 must engage substrate and Hsp110, and hydrolyze ATP for protein disaggregation. Hsp40 must harbor a functional J domain to promote protein disaggregation, but the J domain alone is insufficient. Optimal disaggregase activity is achieved when the Hsp40 can stimulate the ATPase activity of Hsp110 and Hsp70. Finally, Hsp110, Hsp70 and Hsp40 fail to rapidly remodel amyloid forms of the yeast prion protein, Sup35, or the Parkinson's disease protein, alpha-synuclein. However, Hsp110, Hsp70 and Hsp40 enhanced the activity of Hsp104 against these amyloid substrates. Taken together, these findings suggest that Hsp110 fulfils a subset of Hsp104 activities in mammals. Moreover, they suggest that Hsp104 can collaborate with the mammalian disaggregase machinery to rapidly remodel amyloid conformers