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We report the development of a β‐turn mimic that allows the direct formation of cyclic peptides through a spontaneous cyclisation under standard solid phase peptide synthesis (SPPS) cleavage conditions. The mimic is formed via an acylhydrazone, which is either reduced in situ by triisopropylsilane‐trifluoroacetic acid, or which can be isolated and reduced in a separate step. This method uses commercially available reagents and is compatible with manual and automated SPPS methods. The cyclisation is tolerant of polar residues at the C‐terminal position, with the exception of asparagine, for which a subsequent structural rearrangement similar to aspartimide formation was observed. The cyclisation method has been shown to tolerate ring sizes equivalent to 5–10 amino acid residues. We have used this method to design and synthesise potential selective integrin binding sequences with controlled conformations. [ABSTRACT FROM AUTHOR]

Abstract How can we describe and categorize government relationships with pro-government militias (PGMs)? Most research tends to focus on government sponsorship of PGMs. This entails a cooperative relationship and government delegation to PGMs. Yet most government-PGM relations are nuanced, complex, and are often fraught with uncertainty and even conflict and hostility. In this article we discuss the conceptualization of PGMs vis-à-vis a government or state, we then discuss the complexities of government-PGM relations, and then develop a spectrum framework to categorize these relationships. We classify government-PGM relations based on their alignment of interests/objectives, the degree to which a government has control over a PGM and their balance of power, and the extent to which a government provides material support to a PGM. We introduce five categories – government control, delegation, cooperation, acquiescence, and conflict. This spectrum framework aids in a better understanding of the nuances in government-PGM relationships, includes under-explored aspects of their possible relations, such as competition/conflict, and how these relations change over time. [ABSTRACT FROM AUTHOR]

Background: An exponential increase in outpatient telehealth visits occurred early in the pandemic period that has been followed by volumes that, although lower than peak numbers, are substantially greater than the pre-pandemic period. This provided an opportunity to assess provider perceptions regarding the right prevalence going forward and key obstacles to achieving it. Methods: A 10-question survey was distributed to all outpatient providers within the Dartmouth-Hitchcock Health System. Domains included practice location, specialty, professional degree, experience with telehealth, satisfaction, perception of the amount of telehealth that could be adequately delivered going forward, role of audio-only, and obstacles. Results: Three hundred thirty-six providers completed the survey representing 51 specialties. The most common response regarding the proportion of outpatient visits that could be delivered by video going forward was 21–50% (n = 104) followed by 6–20% (n = 99) and >50% (n = 71). A minority of respondents chose ≤5% (n = 17). In terms of the fraction of video visits for which phone was equally effective, a similar percentage of respondents felt that it was 1/10 (22%), 1/4 (20%), or 1/2 (26%) of visits. Fewer felt that all (7%) or 3/4 (15%) of visits were equally effective, and 10% felt that it was none. Common obstacles identified were the need for a physical exam, unique aspects of providers' patients, patient preference, and issues regarding technology and internet speed/connectivity. Conclusions: After a period of exponential growth in virtual visits due to the pandemic, outpatient providers within an academic health system felt that a substantial portion of future visits could be delivered by this modality. [ABSTRACT FROM AUTHOR]

Hydrous Fo91 ringwoodite crystals were synthesized at 20 GPa and high-temperature conditions using a multi-anvil press. Recovered crystals were analyzed using electron microprobe analysis, Raman spectroscopy, infrared spectroscopy, synchrotron Mössbauer spectroscopy, single-crystal X-ray diffraction, and single-crystal Laue neutron diffraction, to carefully characterize the chemistry and crystallography of the samples. Analysis of the combined data sets provides evidence for the presence of tetrahedrally coordinated ferric iron and multiple hydrogen incorporation mechanisms within these blue-colored iron-bearing ringwoodite crystals. Tetrahedral ferric iron is coupled with cation disorder of silicon onto the octahedrally coordinated site. Cation disorder in mantle ringwoodite minerals may be promoted in the presence of water, which could have implications for current models of seismic velocities within the transition zone. Additionally, the presence of tetrahedrally coordinated ferric iron may cause the blue color of many ringwoodite and other high-pressure crystals. [ABSTRACT FROM AUTHOR]

mAbs have revolutionized the treatment of autoimmune disorders. Even though mAbs have shown impressive efficacy in blocking T cell or B cell activation and/or recruitment to sites of inflammation, this group of biologicals are not devoid of adverse effects. The most serious adverse effects include infusion reactions, including the activation of the complement pathway. In this study, we present a detailed structure-function study of an anti-CCL20 humanized IgG1 mAb that neutralizes CCL20 chemokine and prevents the recruitment of Th17 cells to sites of inflammation. We demonstrate that the anti-CCL20 Ab changes significantly following administration to humans and monkeys and exposure to human serum. Analysis of the drug product revealed that the anti-CCL20 Ab has unexpectedly high C1q binding. This high binding was linked to immune complex formation in vivo but not during in vitro serum incubation. The immune complex contained multiple complement components. Anti-CCL20 Ab-mediated, complement-dependent cytotoxicity occurred when the Ab bound to CCL20 tethered to the cell membrane of target cells. Taken together, these results provide a likely cause for the animal toxicity observed. In addition, anti-CCL20 revealed progressive acidification because of N100 (located in CDR) deamidation over time, which did not directly impact Ag binding. Our study demonstrates that the safety profiling of mAbs should include the evaluation of effector functions in addition to typical stressed conditions. [ABSTRACT FROM AUTHOR]

The Church was a powerful institution in early modern times with courts to enforce its laws on the people at large. Most historians, however, consider its disciplinary machinery to be in decline by the 1690s, while Evan Davies claims there was a new vitality in the enforcement of religious conformity in the Diocese of Worcester after the Restoration. What were the nature and extent of the Church's controls over society? Charge sheets in surviving consistory court books show the nature of church concerns and how these changed over time, while analyses of numbers summoned, their attendance at court and completion of business reveal the extent of its controls over society. The article traces trajectories over the seventeenth century to bring a broader perspective than Evan Davies to these questions. It sets Worcester within trends in other dioceses to confirm that the Church was a diminishing force in society. [ABSTRACT FROM AUTHOR]

Thermal SiO2 passivates both moderately and heavily doped silicon surfaces irrespective of the dopant type, which is advantageous in high-efficiency solar cell designs. Commercial photovoltaic cells are submitted to accelerated ageing tests, such as damp-heat exposure, to ensure they maintain their performance for at least 20 yr. We find damp-heat exposure causes a severe and rapid degradation of thermal SiO2 passivation on p+ silicon surfaces. The reaction is so severe that the diffused-region recombination in the degraded state is limited by the diffusion of minority carriers to the Si-SiO2 interface not the density of interface defects Dit. Certainly, this effect renders the thermal-oxide passivation useless if employed on a solar cell. To study the cause of the degradation, we also test the effects of storage in dry heat and room ambient conditions. Examination of the rate of degradation in the tested storage conditions in comparison with modelled diffusion of moisture in SiO2, we find a significant correlation between the time dependent J0e and moisture supplied to the interface, leading us to the conclusion that moisture ingression and subsequent reaction at the SiO2-Si interface are the cause of both damp-heat and room- ambient degradation. [ABSTRACT FROM AUTHOR]

Purpose: To assess a single site's initial experience with SMILE for the treatment of myopic astigmatism and compare outcomes and vector analysis results with the US Food and Drug Administration (FDA) results and published literature. Patients and Methods: Forty-eight eyes (29 patients) with mean preoperative sphere of − 5.11 ± 1.31 diopters (D) and cylinder of − 1.12 ± 0.60 D underwent SMILE. Visual acuity, refractive, and vector analysis outcomes as well as subjective measures were reported at three and twelve months postoperatively and compared with FDA results and the published literature between 2014 and 2020 involving treatment of patients with mean cylinders of >− 0.50 to ≤− 3.00 D. Results: At three and twelve months, 43 and 32 eyes were evaluated, respectively. At twelve months, mean cylinder power was reduced to − 0.38 ± 0.38 D with 78.1% achieving ≤± 0.50 D. Uncorrected distance visual acuity (UDVA) ≥ 20/20 was achieved in 77.4% of eyes by twelve months with 100% achieving ≥ 20/30 UDVA. No loss of corrected distance visual acuity was observed in eyes seen at twelve months. Correction index (CI) at twelve months was 0.90 indicating overall undercorrection of 10%. Twelve-month CI was 0.96, 0.90, and 0.83 in eyes with preoperative cylinders of <− 1.00 D, ≥− 1.00 to <− 2.00 D, and ≥− 2.00 D, respectively. Mean angle of error was − 1.58 ± 11.61° ranging from − 24.22° to 37.75°. Conclusion: We found SMILE to be an effective and safe means of achieving spectacle independence and improving visual acuity in patients with myopic astigmatism. SMILE has the potential for improved clinical outcomes with better nomogram guidance and advancements in technique. However, surgeons must be aware of the potential for undercorrection in with-the-rule astigmatism and at higher preoperative cylinders and as well as the potential for overcorrection in against-the-rule and lower preoperative cylinder astigmatism. [ABSTRACT FROM AUTHOR]

Despite the potential for the chemokine class as therapeutic targets in immune mediated disease, success has been limited. Many chemokines can bind to multiple receptors and many receptors have multiple ligands, with few exceptions. One of those exceptions is CCL20, which exclusively pairs to CCR6 and is associated with several immunologic conditions, thus providing a promising therapeutic target. Following successful evaluation in a single dose, first time in human clinical study, GSK3050002—a humanized IgG1 monoclonal antibody against human CCL20—was evaluated in a 26-week cynomolgus monkey toxicology study. A high incidence of unexpected vascular and organ inflammation was observed microscopically, leading to the decision to halt clinical development. Here we report a dose-responsive increase in the incidence and severity of inflammation in multiple organs from monkeys receiving 30 and 300 mg/kg/week by either subcutaneous or intravenous injection. Histomorphological changes resembled an immune complex-mediated pathology, which is often due to formation of anti-drug antibodies in monkeys receiving a human protein therapeutic and thus not predictive of clinical outcome. However, the presentation was atypical in that there was a clear dose response with a very high incidence of inflammation with a low incidence of ADA that did not correlate well individually. Additionally, the immunohistologic presentation was atypical in that the severity and distribution of tissue inflammation was greater than the numbers of associated immune complexes (i.e., granular deposits). An extensive ex vivo analysis of large molecular weight protein complexes in monkey serum from this study and in human serum samples demonstrated a time-dependent aggregation of GSK3050002, that was not predicted by in vitro assays. The aggregates also contained complement components. These findings support the hypothesis that immune complexes of drug aggregates, not necessarily including anti-drug antibodies, can fix complement, accumulate over time, and trigger immune complex disease. A situation which may have increased clinical relevance than typical anti-drug antibody-associated immune complex disease in monkeys administered human antibody proteins. [ABSTRACT FROM AUTHOR]

George Morley was Bishop of Worcester for only eighteen months but at a critical juncture: the Restoration of the Church and the Monarchy. The purpose of this article is to describe and assess his achievement. The episcopal apparatus had to be revived after fourteen years of abolition. In addition to routine activities, such as institutions of clergy, diocesan visitations, confirmations and the church court, the treatment of intruder clergy and a backlog of building repairs made his agenda particularly challenging. Worcester was an important diocese and was probably seen as a training ground for a top post in the Church. This article surveys Morley's record as far as surviving documents allow and attempts to place it in context. Despite shortcomings, Morley more than fulfilled his promise which no doubt led to his swift translation to Winchester. [ABSTRACT FROM AUTHOR]

Abstract Biotransformation monitoring involves tracking drug modification occurring during in-life studies. Critical Quality Attribute monitoring from forced degraded drug material or in-life sample sets can provide an in-depth assessment of product quality for support in early- or late-stage drug development. For Critical Quality Attribute analysis, biotherapeutic monoclonal antibody (mAb) subunit analysis and peptide mapping liquid chromatography–mass spectrometry (LC-MS) approaches are used, although typically from an in vitro setting (e.g., formulation buffer) not involving biological samples or material. Here, samples from a high-dose rat study (in vivo) are subjected to analysis by ligand binding assay, mAb subunit LC-MS, and peptide mapping by LC-MS. Taken together, data from the 3 analytical approaches provide information regarding drug concentration in circulation, biotransformation, and biotherapeutic drug product quality. The concept of a multitier workflow for preclinical or clinical sample sets can be applied to other biotherapeutic mAb products such as bispecific mAbs, fusions proteins, or antibody-drug conjugates. [ABSTRACT FROM AUTHOR]

Adopted guidelines reflect a harmonised European approach to a specific scientific issue and should reflect the most recent scientific knowledge. However, whilst EU regulations are mandatory for all member states and EU directives must be followed by national laws in line with the directive, EMA guidelines do not have legal force and alternative approaches may be taken, but these obviously require more justification. This new series of the BJCP, developed in collaboration with the EMA, aims to address this issue by providing an annotated version of some relevant EMA guidelines and regulatory documents by experts. Hopefully, this will help in promoting their diffusion and in opening a forum for discussion with our readers. [ABSTRACT FROM AUTHOR]

Responding to burgeoning scholarship examining discrete positive emotions, the overarching goals of the current review are to provide a summary of 28 enjoyable emotions and to offer an initial classification of these emotions into families. The families of discrete enjoyable emotions, many proposed for the first time, are as follows: (1) Self-praising emotions (authentic pride, fiero, naches, feeling respected), (2) other-praising emotions (admiration, elevation, gratitude, inspiration), (3) past-oriented emotions (forgiveness, nostalgia, relief), (4) future-oriented emotions (anticipatory enthusiasm, courage, determination, hope), (5) hazardous emotions (lust, schadenfreude, hubristic pride), (6) affectionate emotions (love, attachment love, tenderness, positive empathy), (7) arousal-defined emotions (euphoria, serenity), (8) violation-elicited emotions (amusement, awe, curiosity, positive surprise).This review describes how the 28 enjoyable emotions were selected, outlines the classification process generating the families of enjoyable emotions, provides a brief summary of current scholarship on each emotion, and concludes with a discussion of fertile future directions. [ABSTRACT FROM AUTHOR]

This article provides an investigation into claims that paramilitary violence in Colombia can pose a threat to the peace agreement signed in 2016 between the Colombian government and the FARC rebels. These claims highlight the capacity for paramilitary groups to 'spoil' the peace deal. Hitherto, however, there is a lack of scholarly research to investigate the potential of paramilitary spoiling. Firstly, this article highlights the flaws in the government's perspective that paramilitarism no longer exists in Colombia. Instead, the government argues that Colombia is plagued by criminal bands (known as BACRIMs). Secondly, through fieldwork interviews and questionnaires conducted in FARC demobilisation camps, together with descriptive data analysed through a uniquely coded dataset on violence in western Colombia, this article supports claims that successor paramilitary groups represent a key spoiler threat to the current government-FARC peace process. On the one hand, the paramilitaries can represent a direct spoiler threat by, for instance, violently targeting demobilising FARC guerrillas. On the other hand, successor paramilitary groups represent a key indirect spoiler threat, as paramilitary violence is exacerbating the root causes of the conflict that the peace deal seeks to address, with negative implications for the prospects for peace. [ABSTRACT FROM AUTHOR]

Bayesian methods have been proposed as a natural fit for pediatric extrapolation, as they allow the incorporation of relevant external data to reduce the required sample size and hence trial burden for the pediatric patient population. In this paper we will discuss our experience and perspectives with these methods in pediatric trials. We will present some of the background and thinking underlying pediatric extrapolation and discuss the use of Bayesian methods within this context. We will present two recent case examples illustrating the value of a Bayesian approach in this setting and present perspectives on some of the issues that we have encountered in these and other cases. [ABSTRACT FROM AUTHOR]

Introduction: Fluid management is a cornerstone of treatment in acute pancreatitis (AP). Methods: Identification of existing randomized prospective trials of patients with AP, in which intravenous fluid management was a significant parameter in the experimental design, was undertaken using the PubMed and ENDOBASE databases. Results: Included patients in the seven studies identified were on the whole very unwell with deaths occurring in six trials. Fluid regimens in AP included crystalloid alone, combinations of crystalloid and colloid and in two studies, plasma. In most studies, patients with premorbid major organ failure and advanced age were excluded. Study entry within 6 h of presentation occurred in three trials. Initial fluid administration rates varied from 1 to 2 mL/kg/h to 15 mL/kg/h. Rapid fluid rates were associated with increased morbidity and mortality except in one study in which a high fluid regimen (20 mL/kg bolus within 4 h of presentation followed by 3 mL/kg) led to a better clinical outcome than a more conservative regimen. Use of Ringer's lactate led to improved surrogate outcome markers compared to that of normal saline in one study. Administration of colloid as part of the fluid management was associated with lower morbidity and lower fluid requirements. Conclusion: Rapid infusion of crystalloid very early in the course of AP may be beneficial but rapid infusion of fluid later in the course of the illness may be deleterious. Colloid administration and the use of Ringer's lactate solution in preference to normal saline may improve outcome. [ABSTRACT FROM AUTHOR]

Three online studies assessed a new approach for increasing help seeking among people with depressive symptomatology (i.e. a positive emotion infusion, PEI). A PEI refers to the induction of positive emotion such that people’s mindsets – including perceptions of help-seeking – are temporarily altered. Study 1 (n = 382) indicated that help-seeking intentions are negatively correlated with depressive symptomatology and positively correlated with elevation and gratitude. Studies 2 and 3 implemented fully randomized experimental designs. In Study 2, two elevation-based (Study 2a, n = 285) and two gratitude-based (Study 2b, n = 338) emotion inductions increased levels of elevation and gratitude, respectively. Results of Study 3a (n = 390) indicate a causal relationship between experiencing the story-based elevation induction and increased help-seeking intentions. The two gratitude-based PEIs (Study 3b, n = 466) were unsuccessful at influencing help-seeking; auxiliary analyses indicate the possibility of iatrogenic effects. Overall, the potential of PEIs was indicated, as was need for caution. [ABSTRACT FROM AUTHOR]

The term elevation (also referred to as moral elevation), described by Thomas Jefferson and later coined by Jonathan Haidt, refers to the suite of feelings people may experience when witnessing an instance of moral beauty. The construct of elevation signifies the emotion felt when a person is a witness to, but not a recipient of, the moral behavior of others. Scholarship examining elevation has burgeoned since Haidt first introduced the construct. Researchers have explored the antecedents of, and outcomes associated with, witnessing instances of moral beauty. The current review will outline the existing scholarship on elevation, highlight conflicting findings, point out critical gaps in the current state of elevation research, and delineate fertile future directions for basic and applied research. Continued investigation of the affective, motivational, and behavioral responses associated with witnessing virtuous actions of others is warranted. [ABSTRACT FROM AUTHOR]

We suspected that corneal nerves were more likely severed with a temporal incision than with a superior incision, and this can contribute to triggering HSV keratitis reactivation.[5] The corneal nerves are derived from the long ciliary nerves of the ophthalmic division of the fifth (trigeminal) cranial nerve; these nerves enter the limbus predominantly at the 9- and 3-o'clock positions. The prevalence was significantly higher with a temporal corneal incision approach than with a superior corneal incision approach; 10 of the 11 patients with HSV keratitis had temporal corneal incisions, and 1 patient had a superotemporal incisional location. We read with great interest the study by Al-Ani et al., in which the authors evaluated factors associated with recurrent herpes simplex virus (HSV)-related keratitis after cataract surgery.[1] In their retrospective study, the authors reported recurrent HSV keratitis after cataract surgery in 17 (45.9%) of the 37 eyes with previous diagnosis of ocular herpes disease. [Extracted from the article]

Phacoemulsification cataract surgery in patients receiving novel oral anticoagulant medications. Modifying hematologic factors to decrease intraocular bleeding (eg, halting anticoagulants) did not significantly affect the intraocular bleeding in clear corneal cataract surgery in our study. We read with great interest the study by Reilly et al., in which the authors described complications and outcomes of clear corneal incision cataract surgery in a large cohort of patients with thrombocytopenia.[1] In their retrospective review, the authors found only 2 cases (1%) of intraoperative iris hemorrhage of 196 eyes from 150 thrombocytopenic patients. [Extracted from the article]

The iron-sulfur cluster containing protein Fumarate and Nitrate Reduction (FNR) is the master regulator for the switch between anaerobic and aerobic respiration in Escherichia coli and many other bacteria. The [4Fe-4S] cluster functions as the sensory module, undergoing reaction with O2 that leads to conversion to a [2Fe-2S] form with loss of high-affinity DNA binding. Here, we report studies of the FNR cluster conversion reaction using time-resolved electrospray ionization mass spectrometry. The data pro- vide insight into the reaction, permitting the detection of cluster conversion intermediates and products, including a [3Fe-3S] cluster and persulfide-coordinated [2Fe-2S] clusters [[2Fe-2S](S)n, where n = 1 or 2]. Analysis of kinetic data revealed a branched mechanism in which cluster sulfide oxidation occurs in parallel with cluster conversion and not as a subsequent, secondary reaction to generate [2Fe-2S](S)n species. This methodology shows great potential for broad application to studies of protein cofactor-small molecule interactions. [ABSTRACT FROM AUTHOR]

Background Vascular endothelial growth factor (VEGF) and its receptors (VEGFR-1 and VEGFR-2) regulate vascular permeability and endothelial cell survival. We hypothesized that hemorrhagic shock (HS) and chronic stress (CS) would increase expression of lung VEGF and its receptors, potentiating pulmonary edema in lung tissue. Materials and methods Male Sprague–Dawley rats aged 8-9 wk were randomized: naïve control, lung contusion (LC), LC followed by HS (LCHS), and LCHS with CS in a restraint cylinder for 2 h/d (LCHS/CS). Animals were sacrificed on days 1 and 7. Expressions of lung VEGF, VEGFR-1, and VEGFR-2 were determined by polymerase chain reaction. Lung Injury Score (LIS) was graded on light microscopy by inflammatory cell counts, interstitial edema, pulmonary edema, and alveolar integrity (range: 0 = normal; 8 = severe injury). Results Seven days after LC, lung VEGF and VEGFR-1 were increased, and lung tissue healed (LIS: 0.8 ± 0.8). However, 7 d after LCHS and LCHS/CS, lung VEGF and VEGFR-1 expressions were decreased. VEGFR-2 was also decreased after LCHS/CS. LIS was elevated 7 d after LCHS and LCHS/CS (6.5 ± 1.0 and 8.2 ± 0.8). Increased LIS after LCHS and LCHS/CS was because of higher inflammatory cell counts, increased interstitial edema, and loss of alveolar integrity, whereas pulmonary edema was unchanged. Conclusions Elevation of lung VEGF and VEGFR-1 expressions after LC alone was associated with healing of injured lung tissue. Expressions of VEGF, VEGFR-1, and VEGFR-2 were reduced after LCHS and LCHS/CS, and injured lung tissue did not heal. Persistent lung injury after severe trauma was because of inflammation rather than pulmonary edema. [ABSTRACT FROM AUTHOR]

Photovoltaic cell and module manufactures optimise their products according to power measurements performed at a set of standard-test conditions. A key parameter for the financing of a solar project is yield under field or realistic conditions. Field testing modules is time consuming and costly. Hence, we develop a methodology for simulating PV module yield based on the optical, thermal and electrical properties of the components, and the module configuration regarding the cell spacing, interconnection and module layers. With our procedure, we model the performance of standard, half cell and encapsulant free modules in different locations. We present results using our cell to module yield framework for 16 different locations in Australia based on one-minute ground measured solar irradiance and ambient temperature values. We find low-light irradiance losses are directly correlated to the number of cloudy days at a given site. The majority of fielded losses are due to temperature effects, which can be predicted by the average temperature at 3 p.m. We note that wind speed is not accounted for and it will be incorporated in future studies. [ABSTRACT FROM AUTHOR]

Purpose: To develop a cohort of patients with T2DM treated with insulin using CPRD to obtain an accurate diagnosis date. This was used to analyse time from T2DM diagnosis to first ever insulin prescription between 01/01/2000 and 30/06/2012, for patients in England and Wales. Methods: Patients aged 18 years and over at diagnosis, were included if prescribed an anti-diabetic drug and were excluded if first diagnosis-specific code was inconsistent with a T2DM diagnosis. Diagnosis codes were split into 8 categories based on whether they related to specific T2DM or non-specific diabetes codes. Patients were excluded if they had non-specific diagnosis codes and were prescribed insulin as their first-ever treatment for diabetes. Descriptive statistics for time from T2DM diagnosis to insulin initiation were calculated. Results: Two hundred and fifty-six codes were identified which were consistent with a first-ever diagnosis of T2DM. 7 codes were considered to clearly define a diagnosis of T2DM, which were reported for 64% of patients. The final cohort comprised 11,917 patients and the median time to first insulin prescription from the date of diagnosis was 4.4 years. Conclusions: A clear definition of cohort development is required to compare and interpret results from studies. Use of diagnosis and product codes is essential when examining use of drugs such as insulin, where competing diagnoses need to be considered separately. [ABSTRACT FROM AUTHOR]

This article examines how civilian defense militias shape violence during civil war. We define civilian defense forces as a sedentary and defensive form of pro-government militia that incumbents often use to harness the participation of civilians during a counterinsurgency campaign. We argue that civilian defense forces reduce the problem of insurgent identification. This leads to a reduction in state violence against civilians. However, we also claim that these actors undermine civilian support for insurgents, which leads to an increase in rebel violence against civilians and overall intensification of conflict. A statistical analysis of government and rebel violence against civilians from 1981 to 2005 and a qualitative assessment of a civilian defense force operating in Iraq from 2005 to 2009 offer strong support for our theoretical claims. These findings provide further insight into pro-government militias and their effects on violence. They also have wider ethical implications for the use of civilian collaborators during civil war. [ABSTRACT FROM AUTHOR]

The report from Kohli et al. ([1]), an impressively large albeit retrospective comparison of endoscopic versus radiological gastrostomy tube placement, confirmed earlier literature, with the risk of colonic perforation being 0.12% and 0.24% and the risk of peritonitis being 1.9% and 2.7% in the endoscopic and radiological groups, respectively. In this regard, it has been my practice for many years to perform an abdominal CT scan on every single patient being considered for gastrostomy. In an exemplary study ([2]) from Missouri, the natural extension of my approach was used with the use of CT scan-guided gastrostomy tube placement in particularly challenging cases. [Extracted from the article]

Raman spectroscopic data were obtained for (Mg,Fe)2SiO4 samples during compression to 57 GPa. Single crystals of San Carlos olivine compressed hydrostatically above 41 GPa showed appearance of a new "defect" peak in the 820–840 cm–1 region associated with SiOSi linkages appearing between adjacent SiO44– tetrahedra to result in five- or sixfold-coordinated silicate species. Appearance of this feature is accompanied by a broad amorphous background. The changes occur at lower pressure than metastable crystalline transitions of end-member Mg2SiO4 forsterite (Fo-I) into Fo-II and Fo-III phases described recently. We complemented our experimental study using density functional theory (DFT) calculations and anisotropic ion molecular dynamics (AIMD) simulations to study the Raman spectra and vibrational density of states (VDOS) of metastably compressed Mg2SiO4 olivine, Fo-II and Fo-III, and quenched melts at high and low pressures. By 54 GPa all sharp crystalline peaks disappeared from observed Raman spectra indicating complete pressure-induced amorphization (PIA). The amorphous (Mg,Fe)2SiO4 spectrum contains Si-O stretching bands at lower wavenumber than expected for SiO44– indicating high coordination of the silicate units. The amorphous spectrum persisted on decompression to ambient conditions but with evidence for reappearance of tetrahedrally coordinated units. Nonhydrostatic compression of polycrystalline olivine samples showed similar appearance of the defect feature and broad amorphous features between 43–44 GPa. Both increased in intensity as the sample was left at pressure overnight but they disappeared during decompression below 17 GPa with recovery of the starting olivine Raman signature. A hydrated San Carlos olivine sample containing 75–150 ppm OH was also studied. Significant broadening of the SiO44– stretching peaks was observed above 43 GPa but without immediate appearance of the defect or broad amorphous features. However, both of these characteristics emerged after leaving the sample at 47 GPa overnight followed by complete amorphization that occurred upon subsequent pressurization to 54 GPa. During decompression the high-density amorphous spectrum was retained to 3 GPa but on final pressure release a spectrum similar to thermally quenched low-pressure olivine glass containing isolated SiO44– groups was obtained. Leaving this sample overnight resulted in recrystallization of olivine. Our experimental data provide new insights into the metastable structural transformations and relaxation behavior of olivine samples including material recovered from meteorites and laboratory shock experiments. [ABSTRACT FROM AUTHOR]

The equation of state of the orthorhombic phase of NiSi with Pmmn symmetry has been determined at room temperature from synchrotron-based X-ray diffraction measurements of its lattice parameters, made in a diamond anvil cell. Measurements were performed up to 44 GPa, using Ne as the pressure medium and Au as the pressure standard. The resulting pressure-volume ( P- V) data have been fitted with a Birch-Murnaghan equation of state of third order to yield V0 = 11.650 (7) Å3 atom−1, K0 = 162 (3) GPa and K0′ = 4.6 (2). In addition, P- V data have been collected on Ni53Si47 in the B20 structure using both Ne and He as the pressure media and Cu and Au as the pressure standards, also to 44 GPa. A fit using the same Birch-Murnaghan equation of state of third order yields V0 = 11.364 (6) Å3 atom−1, K0 = 171 (4) GPa and K0′ = 5.5 (3). [ABSTRACT FROM AUTHOR]

We develop a method for interpolating the optical properties of silicon nitride formed with different deposition parameters. Published refractive index measurements for eight silicon nitride films formed by in-line microwave plasma-enhanced chemical-vapour deposition with a range of ammonia to silane gas-flow ratios are modelled and interpolated. The measurements are fitted by a physical model for the optical properties of silicon nitride. The model considers 16 different silicon-centred, silicon, nitrogen, hydrogen tetrahedron bond configurations in an effective medium with vacuum. An average root mean squared error (RMSE) of 0.36, was calculated when using the physical model, which is high when compared to a simple semi-physical model which achieves an average RMSE of 0.06. The semi-physical model is similar to the tetrahedron model. However, the scale and shifts variables are used as fit parameters compared to being calculated for a physical tetrahedron configuration. The poor fitting of the tetrahedron model empirically suggests that additional bond arrangements need be considered, in particular tetrahedra with vacant bonds. Our global interpolation over the optical properties measured for multiple films mitigates measurement and modelling error. It leads to a smooth optical function with changing gas ratio which aides in optimisation of multi-layer and graded anti-reflection coatings. [ABSTRACT FROM AUTHOR]

Agmatine deiminases (AgDs) catalyze the hydrolytic conversion of agmatine (decarboxylated arginine) to N -carbamoylputrescine with concomitant release of ammonia. These enzymes, which are encoded by some pathogenic bacterial species, confer a competitive survival advantage by virtue of energy production and acid tolerance through agmatine catabolism. Herein we report the development of a clickable activity-based protein profiling (ABPP) probe that targets the AgD encoded by Streptococcus mutans with high selectivity and sensitivity. [ABSTRACT FROM AUTHOR]

This article assesses the effect that leveraging civilian defense force militias has on the dynamics of violence in civil war. We argue that the delegation of security and combat roles to local civilians shifts the primary targets of insurgent violence toward civilians, in an attempt to deter future defections, and re-establish control over the local population. This argument is assessed through an analysis of the Sunni Awakening and ancillary Sons of Iraq paramilitary program. The results suggest that at least in the Al-Anbar province of Iraq, the utilization of the civilian population in counterinsurgent roles had significant implications for the targets of insurgent violence. [ABSTRACT FROM PUBLISHER]

The design of protein sequences that fold into prescribed de novo structures is challenging. General solutions to this problem require geometric descriptions of protein folds and methods to fit sequences to these. The α-helical coiled coils present a promising class of protein for this and offer considerable scope for exploring hitherto unseen structures. For α-helical barrels, which have more than four helices and accessible central channels, many of the possible structures remain unobserved. Here, we combine geometrical considerations, knowledge-based scoring, and atomistic modeling to facilitate the design of new channel-containing α-helical barrels. X-ray crystal structures of the resulting designs match predicted in silico models. Furthermore, the observed channels are chemically defined and have diameters related to oligomer state, which present routes to design protein function. [ABSTRACT FROM AUTHOR]

Cereal straw, including wheat, barley and rice, offers a renewable and sustainable resource stream for a variety of construction products, including compressed board panels, thatched roofing and bales. The successful use of straw bales as thermal insulation within the external envelope of buildings has been demonstrated by the increasing number of successful contemporary projects around the world. However, the warranty, insurance and financing of such projects is often still not as straightforward as competing solutions, which can be attributed to concerns relating to the long-term durability of the straw. This paper presents findings from an on-going experimental study into the condition monitoring of modern straw bale construction, and also reports on a study investigating the degradation behaviour of wheat straw cyclically exposed to elevated humidity levels. The findings of the study provide encouraging insight into the robustness of straw bale construction. [ABSTRACT FROM AUTHOR]

Agmatine deiminases (AgDs) belong to a family of enzymes known as guanidinium group modifying enzymes (GMEs). Many pathogenic bacteria encode an AgD that participates in the catabolism of agmatine (decarboxylated arginine). This catabolism may confer a competitive survival advantage, by virtue of energy production and increased acid tolerance, making this sub-family of enzymes a potential therapeutic target that warrants further study. Herein we report the development of an activity-based protein profiling (ABPP) probe that selectively targets the AgD from Streptococcus mutans . Due to the selectivity and covalent nature of the modification, this probe could prove to be a valuable tool for the study of other AgD family members. [ABSTRACT FROM AUTHOR]

Elevation has garnered empirical support as the emotional response to witnessing moral beauty. The current studies investigated elevation’s construct validity by experimentally testing whether feelings of elevation are distinct from gratitude, another moral and ‘other-praising’ emotion. Study 1 demonstrated that feelings of elevation are distinct from gratitude, serenity (i.e. a secondary comparison condition), and boredom (i.e. a control condition). Study 2 added a behavioral outcome measure in the form of monetary donations to a moral charity. The third study expanded on Study 2 by randomly assigning participants to an elevation or gratitude mood induction and then randomly assigning them to have the opportunity to donate to either a moral or an amoral charity. Together, these studies support Haidt’s conceptualization of elevation, clarify Algoe and Haidt’s qualitative assessment of the emotional differences between elevation and gratitude, and reveal that elevation results in different behavioral responses than gratitude. [ABSTRACT FROM PUBLISHER]

Mentoring is a prosocial behavior in which an experienced person guides someone with less experience. Elevation refers to the responses elicited when a person witnesses others upholding the highest standards of moral virtue. Three experimental studies bring these two domains together. For all three studies, participants were randomly assigned to either read a story of someone exhibiting moral excellence or to a control condition. Participants in the elevation condition reported feeling more elevated, more positive attitudes toward mentoring, less negative attitudes toward mentoring, greater intentions to become a mentor (Study 1); an increased proclivity to gather information about becoming a mentor (Study 2a); and, an increased tendency to engage in mentoring directly via submitting advice to students (Study 2b). In their totality, the current studies link another prosocial outcome with elevation and demonstrate a condition under which individuals are more likely to be motivated to become a mentor. [ABSTRACT FROM AUTHOR]