The Cauchy problem for Schrödinger flows into Kähler manifolds

We prove local well-posedness of the Schrödinger flow from ℝ n into a compact Kähler manifold N with initial data in H[superscript s+1] (ℝ[superscript n],N) for 3≥ [n/2]+4

MRI radiomic features are independently associated with overall survival in soft tissue sarcoma

Purpose: Soft tissue sarcomas (STS) represent a heterogeneous group of diseases, and selection of individualized treatments remains a challenge. The goal of this study was to determine whether radiomic features extracted from magnetic resonance (MR) images are independently associated with overall survival (OS) in STS. Methods and Materials: This study analyzed 2 independent cohorts of adult patients with stage II-III STS treated at center 1 (N = 165) and center 2 (N = 61). Thirty radiomic features were extracted from pretreatment T1-weighted contrast-enhanced MR images. Prognostic models for OS were derived on the center 1 cohort and validated on the center 2 cohort. Clinical-only (C), radiomics-only (R), and clinical and radiomics (C+R) penalized Cox models were constructed. Model performance was assessed using Harrell\u27s concordance index. Results: In the R model, tumor volume (hazard ratio [HR], 1.5) and 4 texture features (HR, 1.1-1.5) were selected. In the C+R model, both age (HR, 1.4) and grade (HR, 1.7) were selected along with 5 radiomic features. The adjusted c-indices of the 3 models ranged from 0.68 (C) to 0.74 (C+R) in the derivation cohort and 0.68 (R) to 0.78 (C+R) in the validation cohort. The radiomic features were independently associated with OS in the validation cohort after accounting for age and grade (HR, 2.4; Conclusions: This study found that radiomic features extracted from MR images are independently associated with OS when accounting for age and tumor grade. The overall predictive performance of 3-year OS using a model based on clinical and radiomic features was replicated in an independent cohort. Optimal models using clinical and radiomic features could improve personalized selection of therapy in patients with STS

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45

Background: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). Case Report: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45. An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of the WDR45 coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls. Discussion: An extended search for deletions should be performed in apparently WDR45-negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia

Protoplanets with core masses below the critical mass fill in their Roche lobe

We study the evolution of a protoplanet of a few earth masses embedded in a protoplanetary disc. If we assume that the atmosphere of the protoplanet, i.e. the volume of gas in hydrostatic equilibrium bound to the core, has a surface radius smaller than the Roche lobe radius, we show that it expands as it accretes both planetesimals and gas at a fixed rate from the nebula until it fills in the Roche lobe. The evolution occurs on a timescale shorter than the formation or migration timescales. Therefore, we conclude that protoplanets of a few earth masses have an atmosphere that extends to the Roche lobe surface, where it matches to the nebula. This is true even when the Bondi radius is smaller than the Roche lobe radius. This is in contrast to the commonly used models in which the static atmosphere extends up to the Bondi radius and is surrounded by a cold accretion flow. As a result, any calculation of the tidal torque exerted by the disc onto the protoplanet should exclude the material present in the Roche lobe, since it is bound to the protoplanet.Comment: 17 pages, 1 figure, accepted by MNRA

The impact of child soldiers on rebel groups’ fighting capacities

Several rebel groups actively recruit children to serve among their ranks. While this constitutes one of the most egregious violations of children’s rights, it remains unclear what impact recruited children have on the fighting capacities of these armed groups. The existing research suggests that, on the one hand, armed groups drafting children might also be militarily effective, since it is cheaper to provide for children, they are more obedient and aggressive than adults, and easily manipulable. On the other hand, children may negatively affect rebel groups’ fighting capacities as they are less proficient combatants than adults and often difficult to control. We add to this debate by systematically analyzing the quantitative evidence on the impact of child soldiers on rebel groups’ fighting capacities. Based on the analysis of newly compiled data on child recruitment by rebel groups between 1989 and 2010, our analyses show that children may actually increase rebel groups’ fighting capacities. That said, rebels’ ability to procure arms and the access to resources seem to be more important determinants of fighting capacity. The authors discuss these findings in light of policy implications and avenues for future research. </jats:p

Neocortical Connectivity during Episodic Memory Formation

During the formation of new episodic memories, a rich array of perceptual information is bound together for long-term storage. However, the brain mechanisms by which sensory representations (such as colors, objects, or individuals) are selected for episodic encoding are currently unknown. We describe a functional magnetic resonance imaging experiment in which participants encoded the association between two classes of visual stimuli that elicit selective responses in the extrastriate visual cortex (faces and houses). Using connectivity analyses, we show that correlation in the hemodynamic signal between face- and place-sensitive voxels and the left dorsolateral prefrontal cortex is a reliable predictor of successful face–house binding. These data support the view that during episodic encoding, “top-down” control signals originating in the prefrontal cortex help determine which perceptual information is fated to be bound into the new episodic memory trace

Pediatric patient asthma-related emergency department visits and admissions in Washington, DC, from 2001–2004, and associations with air quality, socio-economic status and age group

BACKGROUND: The District of Columbia (DC) Department of Health, under a grant from the US Centers for Disease Control and Prevention, established an Environmental Public Health Tracking Program. As part of this program, the goals of this contextual pilot study are to quantify short-term associations between daily pediatric emergency department (ED) visits and admissions for asthma exacerbations with ozone and particulate concentrations, and broader associations with socio-economic status and age group. METHODS: Data included daily counts of de-identified asthma-related pediatric ED visits for DC residents and daily ozone and particulate concentrations during 2001–2004. Daily temperature, mold, and pollen measurements were also obtained. After a cubic spline was applied to control for long-term seasonal trends in the ED data, a Poisson regression analysis was applied to the time series of daily counts for selected age groups. RESULTS: Associations between pediatric asthma ED visits and outdoor ozone concentrations were significant and strongest for the 5–12 year-old age group, for which a 0.01-ppm increase in ozone concentration indicated a mean 3.2% increase in daily ED visits and a mean 8.3% increase in daily ED admissions. However, the 1–4 yr old age group had the highest rate of asthma-related ED visits. For 1–17 yr olds, the rates of both asthma-related ED visits and admissions increased logarithmically with the percentage of children living below the poverty threshold, slowing when this percentage exceeded 30%. CONCLUSION: Significant associations were found between ozone concentrations and asthma-related ED visits, especially for 5–12 year olds. The result that the most significant ozone associations were not seen in the age group (1–4 yrs) with the highest rate of asthma-related ED visits may be related to the clinical difficulty in accurately diagnosing asthma among this age group. We observed real increases in relative risk of asthma ED visits for children living in higher poverty zip codes versus other zip codes, as well as similar logarithmic relationships for visits and admissions, which implies ED over-utilization may not be a factor. These results could suggest designs for future epidemiological studies that include more information on individual exposures and other risk factors

An international randomised controlled trial to compare TARGeted Intraoperative radioTherapy (TARGIT) with conventional postoperative radiotherapy after breast-conserving surgery for women with early-stage breast cancer (the TARGIT-A trial)

Background: Based on our laboratory work and clinical trials we hypothesised that radiotherapy after lumpectomy for breast cancer could be restricted to the tumour bed. In collaboration with the industry we developed a new radiotherapy device and a new surgical operation for delivering single-dose radiation to the tumour bed – the tissues at highest risk of local recurrence. We named it TARGeted Intraoperative radioTherapy (TARGIT). From 1998 we confirmed its feasibility and safety in pilot studies. Objective: To compare TARGIT within a risk-adapted approach with whole-breast external beam radiotherapy (EBRT) over several weeks. Design: The TARGeted Intraoperative radioTherapy Alone (TARGIT-A) trial was a pragmatic, prospective, international, multicentre, non-inferiority, non-blinded, randomised (1 : 1 ratio) clinical trial. Originally, randomisation occurred before initial lumpectomy (prepathology) and, if allocated TARGIT, the patient received it during the lumpectomy. Subsequently, the postpathology stratum was added in which randomisation occurred after initial lumpectomy, allowing potentially easier logistics and a more stringent case selection, but which needed a reoperation to reopen the wound to give TARGIT as a delayed procedure. The risk-adapted approach meant that, in the experimental arm, if pre-specified unsuspected adverse factors were found postoperatively after receiving TARGIT, EBRT was recommended. Pragmatically, this reflected how TARGIT would be practised in the real world. Setting: Thirty-three centres in 11 countries. Participants: Women who were aged ≥ 45 years with unifocal invasive ductal carcinoma preferably ≤ 3.5 cm in size. Interventions: TARGIT within a risk-adapted approach and whole-breast EBRT. Main outcome measures: The primary outcome measure was absolute difference in local recurrence, with a non-inferiority margin of 2.5%. Secondary outcome measures included toxicity and breast cancer-specific and non-breast-cancer mortality. Results: In total, 3451 patients were recruited between March 2000 and June 2012. The following values are 5-year Kaplan–Meier rates for TARGIT compared with EBRT. There was no statistically significant difference in local recurrence between TARGIT and EBRT. TARGIT was non-inferior to EBRT overall [TARGIT 3.3%, 95% confidence interval (CI) 2.1% to 5.1% vs. EBRT 1.3%, 95% CI 0.7% to 2.5%; p = 0.04; Pnon-inferiority = 0.00000012] and in the prepathology stratum (n = 2298) when TARGIT was given concurrently with lumpectomy (TARGIT 2.1%, 95% CI 1.1% to 4.2% vs. EBRT 1.1%, 95% CI 0.5% to 2.5%; p = 0.31; Pnon-inferiority = 0.0000000013). With delayed TARGIT postpathology (n = 1153), the between-group difference was larger than 2.5% and non-inferiority was not established for this stratum (TARGIT 5.4%, 95% CI 3.0% to 9.7% vs. EBRT 1.7%, 95% CI 0.6% to 4.9%; p = 0.069; Pnon-inferiority = 0.06640]. The local recurrence-free survival was 93.9% (95% CI 90.9% to 95.9%) when TARGIT was given with lumpectomy compared with 92.5% (95% CI 89.7% to 94.6%) for EBRT (p = 0.35). In a planned subgroup analysis, progesterone receptor (PgR) status was found to be the only predictor of outcome: hormone-responsive patients (PgR positive) had similar 5-year local recurrence with TARGIT during lumpectomy (1.4%, 95% CI 0.5% to 3.9%) as with EBRT (1.2%, 95% CI 0.5% to 2.9%; p = 0.77). Grade 3 or 4 radiotherapy toxicity was significantly reduced with TARGIT. Overall, breast cancer mortality was much the same between groups (TARGIT 2.6%, 95% CI 1.5% to 4.3% vs. EBRT 1.9%, 95% CI 1.1% to 3.2%; p = 0.56) but there were significantly fewer non-breast-cancer deaths with TARGIT (1.4%, 95% CI 0.8% to 2.5% vs. 3.5%, 95% CI 2.3% to 5.2%; p = 0.0086), attributable to fewer deaths from cardiovascular causes and other cancers, leading to a trend in reduced overall mortality in the TARGIT arm (3.9%, 95% CI 2.7% to 5.8% vs. 5.3%, 95% CI 3.9% to 7.3%; p = 0.099]. Health economic analyses suggest that TARGIT was statistically significantly less costly than EBRT, produced similar quality-adjusted life-years, had a positive incremental net monetary benefit that was borderline statistically significantly different from zero and had a probability of \u3e 90% of being cost-effective. There appears to be little uncertainty in the point estimates, based on deterministic and probabilistic sensitivity analyses. If TARGIT were given instead of EBRT in suitable patients, it might potentially reduce costs to the health-care providers in the UK by £8–9.1 million each year. This does not include environmental, patient and societal costs. Limitations: The number of local recurrences is small but the number of events for local recurrence-free survival is not as small (TARGIT 57 vs. EBRT 59); occurrence of so few events (\u3c 3.5%) also implies that both treatments are effective and any difference is unlikely to be large. Not all 3451 patients were followed up for 5 years; however, more than the number of patients required to answer the main trial question (n = 585) were followed up for \u3e 5 years. Conclusions: For patients with breast cancer (women who are aged ≥ 45 years with hormone sensitive invasive ductal carcinoma that is up to 3.5 cm in size), TARGIT concurrent with lumpectomy within a risk-adapted approach is as effective as, safer than and less expensive than postoperative EBRT. Future work: The analyses will be repeated with longer follow-up. Although this may not change the primary result, the larger number of events may confirm the effect on overall mortality and allow more detailed subgroup analyses. The TARGeted Intraoperative radioTherapy Boost (TARGIT-B) trial is testing whether or not a tumour bed boost given intraoperatively (TARGIT) boost is superior to a tumour bed boost given as part of postoperative EBRT. Trial registration: Current Controlled Trials ISRCTN34086741 and ClinicalTrials.gov NCT00983684. Funding: University College London Hospitals (UCLH)/University College London (UCL) Comprehensive Biomedical Research Centre, UCLH Charities, Ninewells Cancer Campaign, National Health and Medical Research Council and German Federal Ministry of Education and Research (BMBF). From September 2009 this project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 73. See the NIHR Journals Library website for further project information

Entrepreneurs’ mental health and well-being:A review and research agenda

Interest in entrepreneurs’ mental health and well-being (MWB) is growing in recognition of the role of MWB in entrepreneurs’ decision making, motivation, and action. Yet relevant knowledge is dispersed across disciplines, which makes what we currently understand about entrepreneurs’ MWB unclear. In this systematic review I integrate insights from 144 empirical studies. These studies show that research is focused on three research questions: (1) Do different types of entrepreneurs differ in their MWB? What are the (2) antecedents and (3) consequences of entrepreneurs’ MWB? The review systematizes evidence on known antecedents and consequences of entrepreneurs’ MWB but also reveals overlooked and undertheorized sources and outcomes of entrepreneurs’ MWB. The review provides a mapping and framework that advance research on entrepreneurs’ MWB and help to position entrepreneurs’ MWB more centrally in management and entrepreneurship research. It calls for researchers to go beyond applying models developed for employees to understand entrepreneurs. Instead, the findings point the way to developing a dedicated theory of entrepreneurial work and MWB that is dynamic, socialized, and open to considering context and acknowledges variability and fluidity across entrepreneurs’ life domains, as well as the centrality of work for entrepreneurs’ identity