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We report a time-resolved single photon counting (TCSPC) imaging system based on a line-scanning architecture. The system benefits from the high fill-factor, active area, and large dimension of an advanced CMOS single photon avalanche diode (SPAD) array line-sensor. A two-dimensional image is constructed using a moving mirror to scan the line-sensor field-of-view (FOV) across the target, to enable the efficient acquisition of a two-dimensional 0.26 Mpixel TCSPC image. We demonstrate the capabilities of the system for TCSPC imaging and locating objects obscured in scattering media - specifically to locate a series of discrete point sources of light along an optical fibre submerged in a highly scattering solution. We demonstrate that by selectively imaging using early arriving photons which have undergone less scattering than later arriving photons, our TCSPC imaging system is able to locate the position of discrete point sources of light than a non-time-resolved imaging system., 12 pages, 5 figures submitted to Optica: Optics Express

We present a novel implementation of the adaptively annealed thermodynamic integration technique using Hamiltonian Monte Carlo (HMC). Thermodynamic integration with importance sampling and adaptive annealing is an especially useful method for estimating model evidence for problems that use physics-based mathematical models. Because it is based on importance sampling, this method requires an efficient way to refresh the ensemble of samples. Existing successful implementations use binary slice sampling on the Hilbert curve to accomplish this task. This implementation works well if the model has few parameters or if it can be broken into separate parts with identical parameter priors that can be refreshed separately. However, for models that are not separable and have many parameters, a different method for refreshing the samples is needed. HMC, in the form of the MC-Stan package, is effective for jointly refreshing the ensemble under a high-dimensional model. MC-Stan uses automatic differentiation to compute the gradients of the likelihood that HMC requires in about the same amount of time as it computes the likelihood function itself, easing the programming burden compared to implementations of HMC that require explicitly specified gradient functions. We present a description of the overall TI-Stan procedure and results for representative example problems.

BACKGROUND:Despite increasing calls for shared decision making (SDM), the precise mechanisms for its attainment are unclear. Sharing decisions in mental health care may be especially complex. Fluctuations in service user capacity and significant power differences are particular barriers.OBJECTIVE AND DESIGN:We trialled a form of facilitated SDM that aimed to generate patients' treatment preferences in advance of a possible relapse. The 'Joint Crisis Plan' (JCP) intervention was trialled in four mental health trusts in England between 2008 and 2011. This qualitative study used grounded theory methods to analyse focus group and interview data to understand how stakeholders perceived the intervention and the barriers to SDM in the form of a JCP.RESULTS:Fifty service users with psychotic disorders and 45 clinicians participated in focus groups or interviews between February 2010 and November 2011. Results suggested four barriers to clinician engagement in the JCP: (i) ambivalence about care planning; (ii) perceptions that they were 'already doing SDM'; (iii) concerns regarding the clinical 'appropriateness of service users' choices'; and (iv) limited 'availability of service users' choices'. Service users reported barriers to SDM in routine practice, most of which were addressed by the JCP process. Barriers identified by clinicians led to their lack of constructive engagement in the process, undermining the service users' experience.CONCLUSIONS:Future work requires interventions targeted at the engagement of clinicians addressing their concerns about SDM. Particular strategies include organizational investment in implementation of service users' choices and directly training clinicians in SDM communication processes.

This study presents the recent progress made in developing a spiral fiber tracker (SFT) for use in the experiment TREK/E36 planned at the Japan Proton Accelerator Research Complex. This kaon decay experiment uses a stopped positive kaon beam to search for physics beyond the Standard Model through precision measurements of lepton universality and through searches for a heavy sterile neutrino and a dark photon. Detecting and tracking positrons and positive muons from kaon decays are of importance in achieving high-precision measurements; therefore, we designed and are developing the new tracking detector using a scintillating fiber. The SFT was completely assembled, and in a bench test, no dead channel was determined., Proceedings of 2nd International Symposium on Science at J-PARC (J-PARC 2014), to be published in JPS Conf. Proc., 6 pages, 5 figures

PURPOSE:Recent legislation and guidance in England emphasises the importance of service user choice in care planning. However, it is not obvious how best to facilitate choices in care planning, and some clinicians are concerned that service users may make 'unwise' decisions. This study aimed to examine mental health service users' preferences and priorities in the event of a future mental health crisis or relapse.METHOD:Thematic analysis of 221 joint crisis plans (JCP) developed by service users and their clinical team as part of the CRIMSON randomised controlled trial. Participants had a diagnosis of a psychotic disorder, at least one psychiatric admission in the past 2 years, contact with a community mental health team, and complex care needs.RESULTS:Two major categories of preferences were identified: first the manner in which crisis care would be delivered; and second, specific treatment interventions. Most service users requested full involvement in decisions about their care, clear and consistent treatment plans, access to familiar clinicians who knew them well, and to be treated with respect and compassion. Some service users requested hospitalisation, but the majority preferred alternatives. The most frequently preferred intervention was care by a home treatment team. Just under half made a treatment refusal, the majority being for specific medications, alternatives were offered.CONCLUSIONS:Joint crisis planning resulted in service users making choices that were clinically reasonable. The technique employed by JCPs appeared to empower service users by engaging them in a productive dialogue with their clinicians.

Lepton family number violation is tested by searching for $\mu^+\to e^+X^0$ decays among the 5.8$\times 10^8$ positive muon decay events analyzed by the TWIST collaboration. Limits are set on the production of both massless and massive $X^0$ bosons. The large angular acceptance of this experiment allows limits to be placed on anisotropic $\mu^+\to e^+X^0$ decays, which can arise from interactions violating both lepton flavor and parity conservation. Branching ratio limits of order $10^{-5}$ are obtained for bosons with masses of 13 - 80 MeV/c$^2$ and with different decay asymmetries. For bosons with masses less than 13 MeV/c$^{2}$ the asymmetry dependence is much stronger and the 90% limit on the branching ratio varies up to $5.8 \times 10^{-5}$. This is the first study that explicitly evaluates the limits for anisotropic two body muon decays., Comment: 7 pages, 5 figures, 2 tables, accepted by PRD

Thrombolysis is advocated as the treatment of choice for hemodynamically important pulmonary embolism. This paper reports the case of a patient with subacute massive pulmonary embolism in which thrombolysis was not considered appropriate because transesophageal echocardiography demonstrated a patent foramen ovale and impending paradoxical embolism.

The 17 beta-hydroxysteroid dehydrogenase 1 gene (HSD17B1) encodes 17HSD1, which catalyzes the final step of estradiol biosynthesis. Despite the important role of HSD17B1 in hormone metabolism, few epidemiologic studies of HSD17B1 and breast cancer have been conducted. This study includes 5,370 breast cancer cases and 7,480 matched controls from five large cohorts in the Breast and Prostate Cancer Cohort Consortium. We characterized variation in HSD17B1 by resequencing and dense genotyping a multiethnic sample and identified haplotype-tagging single nucleotide polymorphisms (htSNP) that capture common variation within a 33.3-kb region around HSD17B1. Four htSNPs, including the previously studied SNP rs605059 (S312G), were genotyped to tag five common haplotypes in all cases and controls. Conditional logistic regression was used to estimate odds ratios (OR) for disease. We found no evidence of association between common HSD17B1 haplotypes or htSNPs and overall risk of breast cancer. The OR for each haplotype relative to the most common haplotype ranged from 0.98 to 1.07 (omnibus test for association: X-2 = 3.77, P = 0.58, 5 degrees of freedom). When cases were subdivided by estrogen receptor (ER) status, two common haplotypes were associated with ER-negative tumors (test for trend, Ps = 0.0009 and 0.0076; n = 353 cases). HSD17B1 variants that are common in Caucasians are not associated with overall risk of breast cancer; however, there was an association among the subset of ER-negative tumors. Although the probability that these ER-negative findings are false-positive results is high, these findings were consistent across each cohort examined and warrant further study.

The Canadian high acceptance orbit spectrometer (CHAOS) is a unique magnetic spectrometer system recently commissioned for studies of pion induced reactions at TRIUMF. It is based on a cylindrical dipole magnet producing vertical magnetic fields up to 1.6 T. The scattering target is located in the center of the magnet. Charged particle tracks produced by pion interactions there are identified using four concentric cylindrical wire chambers surrounding the target. Particle identification and track multiplicity are determined by cylindrical layers of scintillation counters and lead-glass Cherenkov counters, which also provide a first level trigger. A sophisticated second level trigger system permits pion fluxes in excess of 5 MHz to be employed. The detector subtends 360° in the horizontal plane, and ±7° out of this plane for a solid angle coverage approximately 10% of 4π sr. The momentum resolution delivered by the detector system is 1% (σ).

Major malformations of the human eye, including microphthalmia and anophthalmia, are examples of phenotypes that recur in families yet often show no clear Mendelian inheritance pattern. Defining loci by mapping is therefore rarely feasible. Using a candidate-gene approach, we have identified heterozygous coding-region changes in the homeobox gene OTX2 in eight families with ocular malformations. The expression pattern of OTX2 in human embryos is consistent with the eye phenotypes observed in the patients, which range from bilateral anophthalmia to retinal defects resembling Leber congenital amaurosis and pigmentary retinopathy. Magnetic resonance imaging scans revealed defects of the optic nerve, optic chiasm, and, in some cases, brain. In two families, the mutations appear to have occurred de novo in severely affected offspring, and, in two other families, the mutations have been inherited from a gonosomal mosaic parent. Data from these four families support a simple model in which OTX2 heterozygous loss-of-function mutations cause ocular malformations. Four additional families display complex inheritance patterns, suggesting that OTX2 mutations alone may not lead to consistent phenotypes. The high incidence of mosaicism and the reduced penetrance have implications for genetic counseling.

The TWIST Collaboration has measured the Michel parameter $\rho$ in normal muon decay, $\mu^+ \to e^+ \nu_e \bar{\nu}_{\mu}$. In the Standard Model, $\rho$ = 3/4. Deviations from this value require mixing of left- and right-handed muon and electron couplings in the muon-decay Lagrangian. We find $\rho$ = 0.75080 $\pm$ 0.00044(stat.) $\pm$ 0.00093(syst.) $\pm$ 0.00023, where the last uncertainty represents the dependence of $\rho$ on the Michel parameter $\eta$. This result sets new limits on the $W_L-W_R$ mixing angle in left-right symmetric models., Comment: 4 pages, 3 figures, submitted to PRL

1. If a purpose of photostasis - absorption of a constant number of photons by the retina, regardless of incident light levels - is to maintain rods at saturation during the light period, then in retinal regions where light intensity is low, rhodopsin concentration should be high, and vice versa. 2. Our ocular transmission photometric measurements revealed that the distribution of light intensity across the rat retina was not as simple as had been thought and, furthermore, that the local concentration of rhodopsin had a high negative correlation with the light intensity. 3. The reciprocity between these two parameters leads to nearly uniform rates of photon absorption in rods across the retina.

When grown on Rambach Propylene Glycol Containing Agar (Rambach agar), 216 of 230 (93.9%) Salmonella organisms isolated from patients and 54 of 62 (87.1%) Salmonella stock cultures produced a crimson-colored growth. Of the 14 clinical Salmonella isolates which displayed colors other than crimson, 8 were Salmonella typhi, 2 were Salmonella paratyphi A, and 4 belonged to other commonly isolated serotypes. All eight Salmonella stock cultures which failed to produce a crimson color belonged to rarely isolated serotypes. In contrast, of 83 non-Salmonella stock cultures distributed among 29 bacterial species, none produced a crimson color. These results suggest that while Rambach agar cannot preidentify S. typhi and S. paratyphi A, the medium can be used for the presumptive identification and can assist in the definitive identification of the overwhelming majority of Salmonella isolates.

Insertion mutagenesis identified two negatively acting gene loci which restrict the ability of Rhizobium leguminosarum bv. trifolii TA1 to infect the homologous host Trifolium subterraneum cv. Woogenellup. One locus was confirmed by DNA sequence analysis as the nodM gene, while the other locus, designated csn-1 (cultivar-specific nodulation), is not located on the symbiosis plasmid. The presence of these cultivar specificity loci could be suppressed by the introduction of the nodT gene from ANU843, a related R. leguminosarum bv. trifolii strain. Other nod genes, present in R. leguminosarum bv. viciae (including nodX) and R. meliloti, were capable of complementing R. leguminosarum bv. trifolii TA1 for nodulation on cultivar Woogenellup. Nodulation studies conducted with F2 seedlings from a cross between cultivar Geraldton and cultivar Woogenellup indicated that a single recessive gene, designated rwt1, is responsible for the Nod- association between strain TA1 and cultivar Woogenellup. Parallels can be drawn between this association and gene-for-gene systems common in interactions between plants and biotrophic pathogens.

Small amounts (0·68-2·7 μg.) of 1,25- dihydroxycholecalciferol (1,25-D.H.C.C.), the hormonally active metabolite of vitamin D 3 , or its synthetic analogue 1α-hydroxycholecalciferol (1α-H.C.C.) rapidly corrected the low plasma-calcium and improved symptoms when given daily to two patients with hypoparathyroidism. The rise in plasma-calcium could be maintained for as long as treatment continued but was readily reversible. The efficacy of minute doses of 1,25-D.H.C.C. and 1α-H.C.C. may indicate that the production of biologically active metabolites of vitamin D is impaired in hypoparathyroidism, and could offer advantages in treatment.

The effects of small oral doses (1-2 microgram/day) of 1alpha-hydroxycholecalciferol, given for 1 to 2 years, have been examined in four nondialysed adolescents with chronic renal failure and bone disease. Treatment increased calcium retention and plasma calcium, and decreased plasma levels of alkaline phosphatase, hydroxyproline, and immunoreactive parathyroid hormone. X-ray abnormalities of bone regressed, and 2 patients underwent successful surgical correction of knock-knees; bone histology in these 2 was normal at the time of operation. 2 patients developed hypercalcaemia which promptly reversed when 1alpha-hydroxycholecalciferol was withdrawn. In one patient treatment was initially successful, but later there was biochemical, radiographic, and histological evidence of relapse. Long-term treatment of such patients with 1alpha-hydroxycholecalciferol may be effective and facilitate the surgical correction of deformities, but this is not invariable. Toxic effects are similar to those of vitamin D itself, but are more readily reversible.

1. 1,25-Dihydroxycholecalciferol (1,25-(OH)2-D3) was given at a dose of 5.0 nmol (2.1 μg) daily by mouth for 4–12 days to three patients with hypophosphataemic (type I), vitamin D-resistant rickets. 2. 1,25-(OH)2-D3 increased intestinal absorption and urinary excretion of calcium without significant effect on the renal handling of phosphate or its plasma concentration. 3. It is concluded that in this type of vitamin D-resistant rickets the renal phosphate abnormality is unlikely to be due to diminished endogenous production of 1,25-(OH)2-D3. 4. The difference between this condition and other hypophosphataemic states is discussed.