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A detailed account of the local atomic structure and disorder at 5~K across the phase diagram of the high temperature superconductor K$_x$Fe$_{2-y}$Se$_{2-z}$S$_z$ $(0 \leq z \leq 2)$ is obtained from neutron total scattering and associated atomic pair distribution function (PDF) approaches. Various model independent and model dependent aspects of the analysis reveal a high level of structural complexity on the nanometer length-scale. Evidence is found for considerable disorder in the $c$-axis stacking of the FeSe$_{1-x}$S$_{x}$ slabs without observable signs of turbostratic character of the disorder. In contrast to the related FeCh (Ch = S, Se) type superconductors, substantial Fe-vacancies are present in K$_x$Fe$_{2-y}$Se$_{2-z}$S$_z$, deemed detrimental for superconductivity when ordered. Our study suggests that the distribution of vacancies significantly modifies the iron-chalcogen bond-length distribution, in agreement with observed evolution of the PDF signal. A crossover like transition is observed at a composition of $z\approx1$, from a predominantly vacancy-disordered state at the selenium end to a more vacancy-ordered (VO) phase closer to the sulfur end of the phase diagram. The S-content dependent measures of the local structure are found to exhibit distinct behavior on either side of this crossover, correlating well with the evolution of the superconducting state to that of a magnetic semiconductor towards the $z\approx2$ end. The behavior reinforces the idea of the intimate relationship of correlated Fe-vacancies order in the local structure and the emergent electronic properties., Comment: 15 pages, 11 figures

Mitsubishi's MD-805, a potent and selective inhibitor of thrombin which contains four stereogenic centers, has been the starting point for an optimization program. A systematic synthetic study resulted in thrombin inhibitors achiral at P2 and P3 but with a 10-fold increase in potency over the original lead. A number of 4-substituted piperidines were synthesized and examined as replacements for 2-carboxy-4-methylpiperidine at P2; 4-fluoroethylpiperidine (FEP) among others provided inhibitors (e.g. 45g) of increased potency. An enantioselective route was developed to 3(R)-methyl-1,2,3,4-tetrahydroquinolinesulfonyl chloride. Inhibitors containing this enantiomerically pure P3 (42d) had similar potency to the racemic material and provided support, with modeling studies, for the preparation of the gem 3,3-disubstituted compounds. A series of inhibitors containing the novel 3, 3-dimethyl-1,2,3,4-tetrahydroquinolinesulfonyl (DMTHQS) P3 (Table 5) were synthesized and showed a similar activity profile as the monomethyl series. The combination of P3-DMTHQS, P2-FEP, and P1-arginine (45g) had a K(i) of 6 nM (MD-805 K(i) = 85 nM). In animal models of both venous and arterial thrombosis, one inhibitor (42e) was shown to produce a dose-dependent inhibition of thrombus formation that in some situations was superior to that of MD-805.

We demonstrate long-lived coherence in internal hyperfine states of a single \Ca{43} trapped-ion qubit $[T_2=1.2(2)\s]$, and in external motional states of a single \Ca{40} trapped-ion qubit $[T_2'=0.18(4)\s]$, in the same apparatus. The motional decoherence rate is consistent with the heating rate, which was measured to be 3(1) quanta/sec. Long coherence times in the external motional states are essential for performing high-fidelity quantum logic gates between trapped-ion qubits. The internal-state $T_2$ time that we observe in \Ca{43}, which has not previously been used as a trapped-ion qubit, is about one thousand times longer than that of physical qubits based on \Ca{40} ions. Using a single spin-echo pulse to ``re-phase'' the internal state, we can detect no decoherence after 1\s, implying an effective coherence time $T_2^{\mbox{\tiny SE}} \gtish 45\s$. This compares with timescales in this trap for single-qubit operations of \ish 1\us, and for two-qubit operations of \ish 10\us., Comment: 4 pages, 4 figures

Objectives: To assess: (i) the size of placental transfusion following a 30 s delay in cord clamping following vaginal and Caesarean births; and (ii) the feasibility of delaying cord clamping in the labour ward and particularly in the operating theatre. Methods: Fourty-six infants born at 26–33 weeks gestation were randomized to having the umbilical cord clamped either immediately or 30 s after birth. The venous haematocrit was measured at 1 and at 4 h of age. Results: There were trends towards higher mean haematocrits in the infants following delayed clamping, but these were not significant either at 1 h (55±7.7 vs 52.9±7) or at 4 h of age (55±7 vs 52.5±7). The trends were more marked in the infants born by Caesarean section, and in those born at 26–29 weeks gestation. Conclusions: A 30 s delay in cord clamping is feasible at both vaginal and Caesarean births, but does not lead to the predicted difference in infant haematocrit. Although physiological studies suggest that a placental transfusion of 15–20 mL/kg occurs within 30 s of delivery, these data suggest that future trials should either delay cord clamping for more than 30 s, or should alter the position of the infant in relation to the uterus in order to facilitate the transfusion. Delayed cord clamping is feasible at Caesarean section.

We discuss the use of electromagnetically modified absorption to achieve selective excitation in atoms: that is, the laser excitation of one transition while avoiding simultaneously exciting another transition whose frequency is the same as or close to that of the first. The selectivity which can be achieved in the presence of electromagnetically induced transparency (EIT) is limited by the decoherence rate of the dark state. We present exact analytical expressions for this effect, and also physical models and approximate expressions which give useful insights into the phenomena. When the laser frequencies are near-resonant with the single-photon atomic transitions, EIT is essential for achieving discrimination. When the laser frequencies are far detuned, the `bright' two-photon Raman resonance is important for achieving selective excitation, while the `dark' resonance (EIT) need not be. The application to laser cooling of a trapped atom is also discussed., Comment: 15 pages, 7 figures

Recent inspection of LANDSAT CCT printouts of New Zealand's Wellington Harbour and Cook Strait revealed that the detection of ships and the identification of related ship parameters are possible. Experience has shown that MSS band 7, because of low radiance values from water and the resultant high S/N ratio, is the best MSS band for a "quick look" inspection of CCT printouts for possible ships. Following verification of the target on the other MSS bands the ship's size, orientation, state of motion, and direction of movement, can be determined from the total number of pixels occupied by the target for each MSS band, the orientation of these pixels, and the target's maximum and total pixel radiance values. Although the smallest positively identified vessel was 127 min length, in theory 30 m long vessels should be identifiable under favourable conditions. This paper presents the procedures used for detecting ships, and discusses the problems and limitations of the overall technique as related to ship parameters, sea state and turbidity, pixel overlap, and relative geometric fidelity between pixels.

Unilateral peripheral vestibular dysfunction (UPVD) is characterized by complaints of dizziness, gaze disturbances and balance impairment. Current management includes medication, physical man oeuvres and exercise regimes, the latter known collectively as vestibular rehabilitation. The aim was to assess the effectiveness of vestibular rehabilitation in people with symptomatic UVPD.A systematic review was conducted for the population of adults diagnosed with symptomatic UPVD, living in the community. We searched all relevant databases and trials registers to identify randomized controlled trials comparing vestibular rehabilitation versus control (e.g. placebo), other treatment (non-vestibular rehabilitation, e.g. pharmacological) or another form of vestibular rehabilitation. We considered possible effectiveness in the domains of symptoms (dizziness) or function (activities, quality of life) and where possible combined results in meta-analyses to provide overall estimates of effect.We included 39 studies involving 2441 participants with UPVD in the review. Individual and pooled analyses of the primary outcome (frequency of dizziness) showed a statistically significant effect in favor of vestibular rehabilitation over control or no intervention (odds ratio (OR) 2.67, 95% confidence interval (CI) 1.85 to 3.86). Secondary outcomes measures related to levels of activity or participation showed a strong trend towards significant differences between the groups (standardized mean difference -0.83, 95% CI -1.02 to -0.64). However when movement-based vestibular rehabilitation was compared to physical maneuvers for benign paroxysmal positional vertigo (BPPV), where the latter was shown to be superior in cure rate in the short term (OR 0.19, 95% CI 0.07 to 0.49). There were no reported adverse effects and risk of bias was generally low across the studies.There is moderate to strong evidence that vestibular rehabilitation is a safe, effective management for UPVD. For the specific diagnostic group of BPPV, physical (repositioning) maneuvers are more effective in the short term than exercise-based vestibular rehabilitation; although a combination of the two is effective for longer-term functional recovery. There is insufficient evidence to discriminate between differing forms of vestibular rehabilitation.

Rationale: Although platelets are considered key inflammatory mediators in respiratory diseases, their role in bronchiectasis has not been fully explored. Objectives: We hypothesized that thrombocytosis in stable state may be associated with bronchiectasis severity and worse clinical outcomes. Methods: Patients with bronchiectasis have been enrolled from 10 centers in Europe and Israel, with platelet count recorded during stable state. The primary outcome was 5-year all-cause mortality. Secondary outcomes included exacerbations, hospitalizations, and mortality at 1, 2, and 3-year follow-up. Analyses were conducted using logistic regression after adjustment for confounding variables. Results: Among the 1,771 patients (median age, 67 yr; 63.4% female) included, 136 (7.7%) had thrombocytosis. Patients with thrombocytosis had a significantly higher disease severity, worse quality of life, higher number of exacerbations and hospitalizations, and higher mortality rate at both 3-year (23 [22.8%] vs. 83 [8.5%], respectively; P,0.01) and 5-year (26 [35.1%] vs. 116 [15.9%], respectively; P,0.01) in comparison with those with normal platelet count. Thrombocytosis was significantly associated with hospitalizations because of severe exacerbations (odds ratio [OR], 1.83; 95% confidence interval [CI], 1.20-2.79; P=0.01) after 1-year followup, as well as increased 3-year (OR, 3.06; 95% CI, 1.74-5.39; P,0.01) and 5-year (OR, 2.46; 95% CI, 1.39-4.37; P,0.01) mortality. Conclusions: Platelets represent a cheap and easy-to-evaluate biomarker, and the presence of thrombocytosis during stable state is associated with disease severity, hospitalizations because of exacerbations, poor quality of life, and mortality in adults with bronchiectasis.

Rationale: Testing for underlying etiology is a key part of bronchiectasis management, but it is unclear whether the same extent of testing is required across the spectrum of disease severity. Objectives: The aim of the present study was to identify the etiology of bronchiectasis across European cohorts and according to different levels of disease severity. Methods: We conducted an analysis of seven databases of adult outpatients with bronchiectasis prospectively enrolled at the bronchiectasis clinics of university teaching hospitals in Monza, Italy; Dundee and Newcastle, United Kingdom; Leuven, Belgium; Barcelona, Spain; Athens, Greece; and Galway, Ireland. All the patients at every site underwent the same comprehensive diagnostic workup as suggested by the British Thoracic Society. Measurements and Main Results: Among the 1,258 patients enrolled, an etiology of bronchiectasis was determined in 60%, including postinfective (20%), chronic obstructive pulmonary disease related (15%), connective tissue disease related (10%), immunodeficiency related (5.8%), and asthma related (3.3%). An etiology leading to a change in patient's management was identified in 13% of the cases. No significant differences in the etiology of bronchiectasis were present across different levels of disease severity, with the exception of a higher prevalence of chronic obstructive pulmonary disease-related bronchiectasis (P < 0.001) and a lower prevalence of idiopathic bronchiectasis (P = 0.029) in patients with severe disease. Conclusions: Physicians should not be guided by disease severity in suspecting specific etiologies in patients with bronchiectasis, although idiopathic bronchiectasis appears to be less common in patients with the most severe disease.

Introduction Although bronchiectasis particularly affects people ≥65 years of age, data describing clinical characteristics of the disease in this population are lacking. This study aimed at evaluating bronchiectasis features in older adults and elderly, along with their clinical outcomes. Methods This was a secondary analysis of six European databases of prospectively enrolled adult outpatients with bronchiectasis. Bronchiectasis characteristics were compared across three study groups: younger adults (18–65 years), older adults (66–75 years), and elderly (and ≥76 years). 3-year mortality was the primary study outcome. Results Among 1258 patients enrolled (median age: 66 years; 42.5% males), 50.9% were ≥65 years and 19.1 ≥ 75 years old. Elderly patients were more comorbid, had worse quality of life and died more frequently than the others. Differences were detected among the three study groups with regard to neither the etiology nor the severity of bronchiectasis, nor the prevalence of chronic infection with P. aeruginosa. In multivariate regression model, age (OR: 1.05; p-value

Bronchiectasis is a heterogeneous disease. This study aimed at identifying discrete groups of patients with different clinical and biological characteristics and long-term outcomes.This was a secondary analysis of five European databases of prospectively enrolled adult outpatients with bronchiectasis. Principal component and cluster analyses were performed using demographics, comorbidities, and clinical, radiological, functional and microbiological variables collected during the stable state. Exacerbations, hospitalisations and mortality during a 3-year follow-up were recorded. Clusters were externally validated in an independent cohort of patients with bronchiectasis, also investigating inflammatory markers in sputum.Among 1145 patients (median age 66 years; 40% male), four clusters were identified driven by the presence of chronic infection withPseudomonas aeruginosaor other pathogens and daily sputum: “Pseudomonas” (16%), “Other chronic infection” (24%), “Daily sputum” (33%) and “Dry bronchiectasis” (27%). Patients in the four clusters showed significant differences in terms of quality of life, exacerbations, hospitalisations and mortality during follow-up. In the validation cohort, free neutrophil elastase activity, myeloperoxidase activity and interleukin-1β levels in sputum were significantly different among the clusters.Identification of four clinical phenotypes in bronchiectasis could favour focused treatments in future interventional studies designed to alter the natural history of the disease.

Many simulations of networks in computational neuroscience assume completely homogenous random networks of the Erdös–Rényi type, or regular networks, despite it being recognized for some time that anatomical brain networks are more complex in their connectivity and can, for example, exhibit the “scale-free” and “small-world” properties. We review the most well known algorithms for constructing networks with given non-homogeneous statistical properties and provide simple pseudo-code for reproducing such networks in software simulations. We also review some useful mathematical results and approximations associated with the statistics that describe these network models, including degree distribution, average path length, and clustering coefficient. We demonstrate how such results can be used as partial verification and validation of implementations. Finally, we discuss a sometimes overlooked modeling choice that can be crucially important for the properties of simulated networks: that of network directedness. The most well known network algorithms produce undirected networks, and we emphasize this point by highlighting how simple adaptations can instead produce directed networks. Refereed/Peer-reviewed

Rationale: There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research. Objectives: This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI). Methods: Derivationof theBSI used data fromaprospective cohort study (Edinburgh, UK, 2008-2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253);Monza, Italy (n = 105); and Newcastle, UK (n = 126). Measurements and Main Results: Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 , 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74-0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84-0.91) for hospitalization, respectively. Therewas a clear difference in exacerbation frequency and quality of life using the St. George's Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P