Patient-specific stopping power calibration for proton therapy planning based on single-detector proton radiography.

A simple robust optimizer has been developed that can produce patient-specific calibration curves to convert x-ray computed tomography (CT) numbers to relative stopping powers (HU-RSPs) for proton therapy treatment planning. The difference between a digitally reconstructed radiograph water-equivalent path length (DRRWEPL) map through the x-ray CT dataset and a proton radiograph (set as the ground truth) is minimized by optimizing the HU-RSP calibration curve. The function of the optimizer is validated with synthetic datasets that contain no noise and its robustness is shown against CT noise. Application of the procedure is then demonstrated on a plastic and a real tissue phantom, with proton radiographs produced using a single detector. The mean errors using generic/optimized calibration curves between the DRRWEPL map and the proton radiograph were 1.8/0.4% for a plastic phantom and -2.1/ - 0.2% for a real tissue phantom. It was then demonstrated that these optimized calibration curves offer a better prediction of the water equivalent path length at a therapeutic depth. We believe that these promising results are suggestive that a single proton radiograph could be used to generate a patient-specific calibration curve as part of the current proton treatment planning workflow

Modernizing Conceptions of Valuation and Cognitive-Control Deployment in Adolescent Risk Taking

Heightened risk taking in adolescence has long been attributed to valuation systems overwhelming the deployment of cognitive control. However, this explanation of why adolescents engage in risk taking is insufficient given increasing evidence that risk-taking behavior can be strategic and involve elevated cognitive control. We argue that applying the expected-value-of-control computational model to adolescent risk taking can clarify under what conditions control is elevated or diminished during risky decision-making. Through this lens, we review research examining when adolescent risk taking might be due to—rather than a failure of—effective cognitive control and suggest compelling ways to test such hypotheses. This effort can resolve when risk taking arises from an immaturity of the control system itself, as opposed to arising from differences in what adolescents value relative to adults. It can also identify promising avenues for channeling cognitive control toward adaptive outcomes in adolescence

The biomechanical role of the chondrocranium and the material properties of cartilage

The chondrocranium is the cartilage component of the vertebrate braincase. Among jawed vertebrates it varies greatly in structure, mineralisation, and in the extent to which it is replaced by bone during development. In mammals, birds, and some bony fish, most of the chondrocranium is replaced by bone whereas in lizards, amphibians, and chondrichthyan fish it may remain a significant part of the braincase complex in adulthood. To what extent this variation relates to differences in skull biomechanics is poorly understood. However, there have been examinations of chondrocranium histology, in vivo strain, and impact on rostrum growth following partial removal of the chondrocranium. These studies have led to suggestions that the chondrocranium may provide structural support or serve to dampen external loads. Advances in computing-power have also facilitated an increase in the number of three-dimensional computer-based models. These models can be analysed (in silico) to test specific biomechanical hypotheses under specified loading conditions. However, representing the material properties of cartilage is still problematic because these properties differ according to the speed and direction of loading. The relationship between stress and strain is also non-linear. Nevertheless, analyses to date suggest that the chondrocranium does not provide a vertical support in lizards but it may serve to absorb some loads in humans. We anticipate that future models will include ever more detailed representations of the loading, anatomy, and material properties, in tandem with rigorous forms of model validation. However, comparison among a wider range of vertebrate subjects should also be pursued, in particular larvae, juveniles, and very small adult animals

Exploring Norms in Agile Software Teams

The majority of software developers work in teams and are thus influenced by team norms. Norms are shared expectations of how to behave and regulate the interaction between team members. Our aim of this study is to gain more knowledge about team norms in software teams and to increase the understanding of how norms influence teamwork in agile software development projects. We conducted a study of norms in four agile teams located in Norway and Malaysia. The analysis of 22 interviews revealed that we could extract a varied set of both injunctive and descriptive norms. Our results suggest that team norms have an important role in enabling team performance.acceptedVersio

Is group cognitive behaviour therapy for postnatal depression evidence-based practice? A systematic review

Background: There is evidence that psychological therapies including cognitive behaviour therapy (CBT) may be effective in reducing postnatal depression (PND) when offered to individuals. In clinical practice, this is also implemented in a group therapy format, which, although not recommended in guidelines, is seen as a cost-effective alternative. To consider the extent to which group methods can be seen as evidence-based, we systematically review and synthesise the evidence for the efficacy of group CBT compared to currently used packages of care for women with PND, and we discuss further factors which may contribute to clinician confidence in implementing an intervention. Methods: Seventeen electronic databases were searched. All full papers were read by two reviewers and a third reviewer was consulted in the event of a disagreement on inclusion. Selected studies were quality assessed, using the Cochrane Risk of Bias Tool, were data extracted by two reviewers using a standardised data extraction form and statistically synthesised where appropriate using the fixed-effect inverse-variance method. Results: Seven studies met the inclusion criteria. Meta-analyses showed group CBT to be effective in reducing depression compared to routine primary care, usual care or waiting list groups. A pooled effect size of d = 0.57 (95% CI 0.34 to 0.80, p < 0.001) was observed at 10–13 weeks post-randomisation, reducing to d = 0.28 (95% CI 0.03 to 0.53, p = 0.025) at 6 months. The non-randomised comparisons against waiting list controls at 10–13 weeks was associated with a larger effect size of d = 0.94 (95% CI 0.42 to 1.47, p < 0.001). However due to the limitations of the available data, such as ill-specified definitions of the CBT component of the group programmes, these results should be interpreted with caution. Conclusions: Although the evidence available is limited, group CBT was shown to be effective. We argue, therefore, that there is sufficient evidence to implement group CBT, conditional upon routinely collected outcomes being benchmarked against those obtained in trials of individual CBT, and with other important factors such as patient preference, clinical experience, and information from the local context taken into account when making the treatment decision

A systems approach to model natural variation in reactive properties of bacterial ribosomes

<p>Abstract</p> <p>Background</p> <p>Natural variation in protein output from translation in bacteria and archaea may be an organism-specific property of the ribosome. This paper adopts a systems approach to model the protein output as a measure of specific ribosome reactive properties in a ribosome-mediated translation apparatus. We use the steady-state assumption to define a transition state complex for the ribosome, coupled with mRNA, tRNA, amino acids and reaction factors, as a subsystem that allows a focus on the completed translational output as a measure of specific properties of the ribosome.</p> <p>Results</p> <p>In analogy to the steady-state reaction of an enzyme complex, we propose a steady-state translation complex for mRNA from any gene, and derive a maximum specific translation activity, <it>T</it>_{<it>a</it>(max)}, as a property of the ribosomal reaction complex. <it>T</it>_{<it>a</it>(max)}has units of <it>a</it>-protein output per time per <it>a</it>-specific mRNA. A related property of the ribosome, <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula>, has units of <it>a</it>-protein per time per total RNA with the relationship <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> = <it>ρ</it>_{<it>a </it>}<it>T</it>_{<it>a</it>(max)}, where <it>ρ</it>_{<it>a </it>}represents the fraction of total RNA committed to translation output of <it>P</it>_{<it>a </it>}from gene <it>a </it>message. <it>T</it>_{<it>a</it>(max)}as a ribosome property is analogous to <it>k</it>_catfor a purified enzyme, and <inline-formula><m:math name="1752-0509-2-62-i1" xmlns:m="http://www.w3.org/1998/Math/MathML"><m:semantics><m:mrow><m:msub><m:mover accent="true"><m:mi>T</m:mi><m:mo>˜</m:mo></m:mover><m:mrow><m:mi>a</m:mi><m:mo stretchy="false">(</m:mo><m:mi>max</m:mi><m:mo>⁡</m:mo><m:mo stretchy="false">)</m:mo></m:mrow></m:msub></m:mrow><m:annotation encoding="MathType-MTEF"> MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi=xH8viVGI8Gi=hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY=rqGqVepae9pg0db9vqaiVgFr0xfr=xfr=xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGafmivaqLbaGaadaWgaaWcbaGaemyyaeMaeiikaGIagiyBa0MaeiyyaeMaeiiEaGNaeiykaKcabeaaaaa@3464@</m:annotation></m:semantics></m:math></inline-formula> is analogous to enzyme specific activity in a crude extract.</p> <p>Conclusion</p> <p>Analogy to an enzyme reaction complex led us to a ribosome reaction model for measuring specific translation activity of a bacterial ribosome. We propose to use this model to design experimental tests of our hypothesis that specific translation activity is a ribosomal property that is subject to natural variation and natural selection much like <it>V</it>_maxand <it>K</it>_mfor any specific enzyme.</p

Epidemic infectious gastrointestinal illness aboard U.S. Navy ships deployed to the Middle East during peacetime operations – 2000–2001

BACKGROUND: Infectious gastrointestinal illness (IGI) outbreaks have been reported in U.S. Navy ships and could potentially have an adverse mission impact. Studies to date have been anecdotal. METHODS: We conducted a retrospective analysis of weekly reported disease and non-battle injury health data collected in 2000 – 2001 from 44 U.S. Navy ships while sailing in the 5(th )Fleet (Persian Gulf and nearby seas). RESULTS: During this period, 11 possible IGI outbreaks were identified. Overall, we found 3.3 outbreaks per 100 ship-weeks, a mean outbreak duration of 4.4 weeks, and a mean cumulative ship population attack rate of 3.6%. Morbidity, represented by days lost due to personnel being placed on sick-in-quarters status, was higher during outbreak weeks compared to non-outbreak weeks (p = 0.002). No clear seasonal distribution was identified. CONCLUSION: Explosive outbreaks due to viruses and bacteria with the potential of incapacitating large proportions of the crew raise serious concerns of mission impact and military readiness

Objectively assessed physical activity and subsequent health service use of UK adults aged 70 and over: A four to five year follow up study

Objectives: To examine the associations between volume and intensity of older peoples' physical activity, with their subsequent health service usage over the following four to five years. Study Design: A prospective cohort design using baseline participant characteristics, objectively assessed physical activity and lower limb function provided by Project OPAL (Older People and Active Living). OPAL-PLUS provided data on numbers of primary care consultations, prescriptions, unplanned hospital admissions, and secondary care referrals, extracted from medical records for up to five years following the baseline OPAL data collection. Participants and Data Collection: OPAL participants were a diverse sample of 240 older adults with a mean age of 78 years. They were recruited from 12 General Practitioner surgeries from low, middle, and high areas of deprivation in a city in the West of England. Primary care consultations, secondary care referrals, unplanned hospital admissions, number of prescriptions and new disease diagnoses were assessed for 213 (104 females) of the original 240 OPAL participants who had either consented to participate in OPAL-PLUS or already died during the follow-up period. Results: In regression modelling, adjusted for socio-economic variables, existing disease, weight status, minutes of moderate-to-vigorous physical activity (MVPA) per day predicted subsequent numbers of prescriptions. Steps taken per day and MVPA also predicted unplanned hospital admissions, although the strength of the effect was reduced when further adjustment was made for lower limb function. Conclusions: Community-based programs are needed which are successful in engaging older adults in their late 70s and 80s in more walking, MVPA and activity that helps them avoid loss of physical function. There is a potential for cost savings to health services through reduced reliance on prescriptions and fewer unplanned hospital admissions. © 2014 Simmonds et al

Hsp90β inhibition modulates nitric oxide production and nitric oxide-induced apoptosis in human chondrocytes

<p>Abstract</p> <p>Background</p> <p>Hsp90β is a member of the Hsp90 family of protein chaperones. This family plays essential roles in the folding, maturation and activity of many proteins that are involved in signal transduction and transcriptional regulation. The role of this protein in chondrocytes is not well understood, although its increase in osteoarthritic cells has been reported. The present study aimed to explore the role of Hsp90β in key aspects of OA pathogenesis.</p> <p>Methods</p> <p>Human OA chondrocytes were isolated from cartilage obtained from patients undergoing joint replacement surgery, and primary cultured. Cells were stimulated with proinflammatory cytokines (IL-1β or TNF-α) and nitric oxide donors (NOC-12 or SNP). For Hsp90β inhibition, two different chemical inhibitors (Geldanamycin and Novobiocin) were employed, or siRNA transfection procedures were carried out. Gene expression was determined by real-time PCR, apoptosis was quantified by flow cytometry and ELISA, and nitric oxide (NO) production was evaluated by the Griess method. Indirect immunofluorescence assays were performed to evaluate the presence of Hsp90β in stimulated cells.</p> <p>Results</p> <p>Hsp90β was found to be increased by proinflammatory cytokines. Inhibition of Hsp90β by the chemicals Geldanamycin (GA) and Novobiocin (NB) caused a dose-dependent decrease of the NO production induced by IL-1β in chondrocytes, up to basal levels. Immunofluorescence analyses demonstrate that the NO donors NOC-12 and SNP also increased Hsp90β. Chemical inhibition or specific gene silencing of this chaperone reduced the DNA condensation and fragmentation, typical of death by apoptosis, that is induced by NO donors in chondrocytes.</p> <p>Conclusions</p> <p>The present results show how Hsp90β modulates NO production and NO-mediated cellular death in human OA chondrocytes.</p