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We have recently reported the synthesis and application of boron–nitrogen dihydroindeno[1,2-b]fluorene derivatives as acceptors in organic photovoltaic devices. Their modest observed efficiencies may be related to the properties of their reduced congeners. In this work, we report two new members of this family of compounds prepared via the electrophilic borylation of 2,5-di- p-tolylpyrazine followed by an arylation of the boron center with ZnAr2 reagents. Two derivatives, 1 (Ar = 2,4,6-F3C6H2) and 2 (Ar = C6F5) were synthesized, and their radical anions, 1•− and 2•−, were formed via chemical reductions with CoCp*2 and CoCp2, respectively. Through comparison of structural parameters, as well as spectroscopic and computational data, the unpaired electron in the radical anions is localized in the planar core of the molecule, and dimerization is disfavored as a result. However, unlike the neutral starting materials, 1•− and 2•− are reactive toward ambient atmosphere. These observations suggest that the reduced compounds are stable toward intrinsic degradation pathways but subject to extrinsic degradation in device operation.

Aims Past research suggests that people report a greater desire to consume alcohol when they experience social threat—or threats to their social selves, such as social exclusion. Nevertheless, experimental research on the role of social threat in alcohol consumption is limited. The present study examined the causal relationship between social threat and wine consumption. Methods Undergraduate students (N = 83; Mage = 21.8 years old, SDage = 1.62 years old; 72.3% women; 61.4% Latinx/Hispanic) participated in a study under the pretense that they were in a focus group gauging students’ opinions of a bar being constructed at their university. During the study, participants and two confederate researchers completed a group activity in which they selected design elements for the bar. Participants were randomly assigned to one of two conditions. In the social threat condition, confederates rejected participants’ design choices and socially excluded them during a follow-up task. In the social acceptance condition, confederates supported participants’ choices and did not socially exclude them. All participants then completed a wine taste test. Results Contrary to predictions, an independent-samples t-test revealed that participants who experienced social threat consumed significantly less wine than those who were socially accepted, t(81) = −2.22, P = 0.03, d = −0.49. Furthermore, a linear regression test revealed that this effect persisted even when controlling for typical alcohol-consumption behavior, b = 56.09, t = −2.50, P = 0.02, d = −0.61. Conclusion The relationship between social threat and alcohol consumption may be more nuanced than anticipated. Discussion centers around two potential moderators including positive affect and identity.

ImportanceMortality prediction among critically ill patients in resource limited settings is difficult. Identifying the best mortality prediction tool is important for counseling patients and families, benchmarking quality improvement efforts, and defining severity of illness for clinical research studies.ObjectiveCompare predictive capacity of the Modified Early Warning Score (MEWS), Universal Vital Assessment (UVA), Tropical Intensive Care Score (TropICS), Rwanda Mortality Probability Model (R-MPM), and quick Sequential Organ Failure Assessment (qSOFA) for hospital mortality among adults admitted to a medical-surgical intensive care unit (ICU) in rural Kenya. We performed a pre-planned subgroup analysis among ICU patients with suspected infection.Design, setting, and participantsProspective single-center cohort study at a tertiary care, academic hospital in Kenya. All adults 18 years and older admitted to the ICU January 2018–June 2019 were included.Main outcomes and measuresThe primary outcome was association of clinical prediction tool score with hospital mortality, as defined by area under the receiver operating characteristic curve (AUROC). Demographic, physiologic, laboratory, therapeutic, and mortality data were collected. 338 patients were included, none were excluded. Median age was 42 years (IQR 33–62) and 61% (n = 207) were male. Fifty-nine percent (n = 199) required mechanical ventilation and 35% (n = 118) received vasopressors upon ICU admission. Overall hospital mortality was 31% (n = 104). 323 patients had all component variables recorded for R-MPM, 261 for MEWS, and 253 for UVA. The AUROC was highest for MEWS (0.76), followed by R-MPM (0.75), qSOFA (0.70), and UVA (0.69) (p < 0.001). Predictive capacity was similar among patients with suspected infection.Conclusion and relevanceAll tools had acceptable predictive capacity for hospital mortality, with variable observed availability of the component data. R-MPM and MEWS had high rates of variable availability as well as good AUROC, suggesting these tools may prove useful in low resource ICUs.

Although resting-state functional magnetic resonance imaging (rsfMRI) has the potential to offer insights into changes in functional connectivity networks after traumatic brain injury (TBI), there are few studies that examine the effects of moderate TBI for monitoring functional recovery in experimental TBI, and thus the neural correlates of brain recovery from moderate TBI remain incompletely understood. Non-invasive rsfMRI was used to longitudinally investigate changes in interhemispheric functional connectivity (IFC) after a moderate TBI to the unilateral sensorimotor cortex in rats (n = 9) up to 14 days. Independent component analysis of the rsfMRI data was performed. Correlations of rsfMRI sensorimotor networks were made with changes in behavioral scores, lesion volume, and T2- and diffusion-weighted images across time. TBI animals showed less localized rsfMRI patterns in the sensorimotor network compared to sham (n = 6) and normal (n = 5) animals. rsfMRI clusters in the sensorimotor network showed less bilateral symmetry compared to sham and normal animals, indicative of IFC disruption. With time after injury, many of the rsfMRI patterns in the sensorimotor network showed more bilateral symmetry, indicative of IFC recovery. The disrupted IFC in the sensorimotor and subsequent partial recovery showed a positive correlation with changes in behavioral scores. Overall, rsfMRI detected widespread disruption and subsequent recovery of IFC within the sensorimotor networks post-TBI, which correlated with behavioral changes. Therefore, rsfMRI offers the means to probe functional brain reorganization and thus has the potential to serve as an imaging marker to longitudinally stage TBI and monitor for novel treatments.

Post transition metal chalcohalides are an emerging class of semiconductor materials for optoelectronic applications. Within this class, bismuth oxyiodide (BiOI) is of particular interest due to its high environmental stability, low toxicity, and defect tolerance considered typical of ‘ns2’ materials. Here we fabricate BiOI thin films using a solution-processed method that affords pin-hole free highly pure films without any residual carbon or other contaminant species. Based on these films, solution processed all-inorganic solar cells with an architecture ITO/NiO x /BiOI/ZnO/Al are fabricated for the first time. Additional device improvements are realised by templating BiOI thin film growth to attain efficiencies that rival some of the best vacuum deposited devices. The BiOI thin films and devices outlined here are an excellent platform for the further development of solution processed bismuth chalcohalide optoelectronic devices.

Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement). Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms. A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up. The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.

Aim Phenomena within the psychosis continuum that varies in frequency/duration/intensity have been increasingly identified. Different terms describe these phenomena, however there is no standardization within the terminology. This review evaluated the definitions and assessment tools of seven terms - (i) 'psychotic experiences'; (ii) 'psychotic-like experiences'; (iii) 'psychotic-like symptoms'; (iv) 'attenuated psychotic symptoms'; (v) 'prodromal psychotic symptoms'; (vi) 'psychotic symptomatology'; and (vii) 'psychotic symptoms'. Methods EMBASE, MEDLINE, and CINAHL were searched during February-March 2019. Inclusion criteria included 1989-2019, full text, human, and English. Papers with no explicit definition or assessment tool, duplicates, conference abstracts, systematic reviews, meta-analyses, or no access were excluded. Results A total of 2238 papers were identified and of these, 627 were included. Definitions and assessment tools varied, but some trends were found. Psychotic experiences and psychotic-like experiences were transient and mild, found in the general population and those at-risk. Psychotic-like symptoms were subthreshold and among at-risk populations and non-psychotic mental disorders. Attenuated psychotic symptoms were subthreshold but associated with distress, risk, and help-seeking. Prodromal psychotic symptoms referred to the prodrome of psychotic disorders. Psychotic symptomatology included delusions and hallucinations within psychotic disorders. Psychotic symptoms was the broadest term, encompassing a range of populations but most commonly involving hallucinations, delusions, thought disorder, and disorganization. Discussion A model for conceptualizing the required terms is proposed and future directions needed to advance this field of research are discussed.

We have recently reported the synthesis and application of boron-nitrogen dihydroindeno[1,2-b]fluorene derivatives as acceptors in organic photovoltaic (OPV) devices. Their modest observed efficiencies may be related to the properties of their reduced congeners. In this work, we report two new members of this family of compounds prepared via the electrophilic borylation of 2,5-di-p-tolylpyrazine followed by an arylation of the boron centre with ZnAr2 reagents. Two derivatives, 1 (Ar = 2,4,6-F3C6H2) and 2 (Ar = C6F5) were synthesized, and their radical anions, 1•− and 2•−, were formed via chemical reductions with CoCp*2 and CoCp2, respectively. Through comparison of structural parameters, as well as spectroscopic and computational data, the unpaired electron in the radical anions is localized in the planar core of the molecule, and dimerization is disfavored as a result. However, unlike the neutral starting materials, 1•− and 2•− are reactive towards ambient atmosphere. These observations suggest that the reduced compounds are stable towards intrinsic degradation pathways but subject to extrinsic degradation in device operation.

Introduction Cinnamaldehyde (CA) elicits itch sensation in humans. We investigated if CA elicits scratching behavior in mice and determined the roles for TRPV1, TRPA1, and TRPV4. Materials and methods Scratching behavior elicited by intradermal injection of CA was assessed in wildtype (WT) mice and knockout (KO) mice lacking TRPV1, TRPA1, TRPV4, or deficient in mast cells. We also assessed scratching and wet dog shakes elicited by low-threshold mechanical stimulation of skin treated topically with CA or vehicle. Using calcium imaging we tested if CA activates dorsal root ganglion (DRG) neurons of each genotype. Results Intradermal cheek injection of CA elicited dose-dependent hindlimb scratch bouts, with fewer forelimb wipes and facial groom bouts that were not dose-dependent. CA elicited significantly fewer scratch bouts in TRPV1 and TRPV4 KO mice, but not TRPA1KOs, compared with WTs. There were no sex differences across genotypes. The histamine H1 antagonist cetirizine did not affect CA-evoked scratching, which was normal in mast cell deficient mice, indicating lack of histamine involvement. Scores for alloknesis were significantly greater following topical application of CA compared with vehicle. Post-CA alloknesis scores were significantly higher in TRPV4KOs of both sexes and in female TRPV1 and TRPA1KOs, compared with WTs. Low threshold mechanical stimuli also elicited significantly more wet dog shakes in mice treated topically with 20% CA, with significantly fewer in TRPV1, TRPA1, and TRPV4KOs compared with WTs. In calcium imaging studies, CA excited 24% of WT DRG cells, significantly fewer (11.5%) in cells from TRPV4KOs, and none in TRPA1KOs. Responses of cells of all genotypes exhibited significant sensitization to repeated CA stimulation. Sensitization was significantly enhanced by IL-4, which itself excited 16% of WT DRG cells and none from TRPA1KOs. Discussion The results indicate that TRPA1 is dispensable for CA-evoked scratching, which depends partly on TRPV1 and TRPV4.

Osteoarthritis (OA) is a leading cause of chronic disability. It is a progressive disease, involving pathological changes to the entire joint, resulting in joint pain, stiffness, swelling, and loss of mobility. There is currently no disease-modifying pharmaceutical treatment for OA, and the treatments that do exist suffer from significant side effects. An increasing understanding of the molecular pathways involved in OA is leading to many potential drug targets. However, both current and new therapies can benefit from a targeted approach that delivers drugs selectively to joints at therapeutic concentrations, while limiting systemic exposure to the drugs. Delivery systems including hydrogels, liposomes, and various types of particles have been explored for intra-articular drug delivery. This review will describe progress over the past several years in the development of polymer-based particles for OA treatment, as well as their in vitro, in vivo, and clinical evaluation. Systems based on biopolymers such as polysaccharides and polypeptides, as well as synthetic polyesters, poly(ester amide)s, thermoresponsive polymers, poly(vinyl alcohol), amphiphilic polymers, and dendrimers will be described. We will discuss the role of particle size, biodegradability, and mechanical properties in the behavior of the particles in the joint, and the challenges to be addressed in future research.

BackgroundThe large volume and suboptimal image quality of portable chest X-rays (CXRs) as a result of the COVID-19 pandemic could post significant challenges for radiologists and frontline physicians. Deep-learning artificial intelligent (AI) methods have the potential to help improve diagnostic efficiency and accuracy for reading portable CXRs.PurposeThe study aimed at developing an AI imaging analysis tool to classify COVID-19 lung infection based on portable CXRs.Materials and methodsPublic datasets of COVID-19 (N = 130), bacterial pneumonia (N = 145), non-COVID-19 viral pneumonia (N = 145), and normal (N = 138) CXRs were analyzed. Texture and morphological features were extracted. Five supervised machine-learning AI algorithms were used to classify COVID-19 from other conditions. Two-class and multi-class classification were performed. Statistical analysis was done using unpaired two-tailedttests with unequal variance between groups. Performance of classification models used the receiver-operating characteristic (ROC) curve analysis.ResultsFor the two-class classification, the accuracy, sensitivity and specificity were, respectively, 100%, 100%, and 100% for COVID-19 vs normal; 96.34%, 95.35% and 97.44% for COVID-19 vs bacterial pneumonia; and 97.56%, 97.44% and 97.67% for COVID-19 vs non-COVID-19 viral pneumonia. For the multi-class classification, the combined accuracy and AUC were 79.52% and 0.87, respectively.ConclusionAI classification of texture and morphological features of portable CXRs accurately distinguishes COVID-19 lung infection in patients in multi-class datasets. Deep-learning methods have the potential to improve diagnostic efficiency and accuracy for portable CXRs.

BACKGROUND Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are increasingly affecting younger populations, particularly African Americans in the southern United States. Access to preventive and therapeutic services, biological factors, and social determinants of health (ie, structural racism, resource limitation, residential segregation, and discriminatory practices) all combine to exacerbate health inequities and their resultant disparities in morbidity and mortality. These factors manifest early in life and have been shown to impact health trajectories into adulthood. Early detection of and intervention in emerging risk offers the best hope for preventing race-based differences in adult diseases. However, young-adult populations are notoriously difficult to recruit and retain, often because of a lack of knowledge of personal risk and a low level of concern for long-term health outcomes. OBJECTIVE This study aims to develop a system design for the MOYO mobile platform. Further, we seek to addresses the challenge of primordial prevention in a young, at-risk population (ie, Southern-urban African Americans). METHODS Urban African Americans, aged 18 to 29 years (n=505), participated in a series of co-design sessions to develop MOYO prototypes (ie, HealthTech Events). During the sessions, participants were orientated to the issues of CVD risk health disparities and then tasked with wireframing prototype screens depicting app features that they considered desirable. All 297 prototype screens were subsequently analyzed using NVivo 12 (QSR International), a qualitative analysis software. Using the grounded theory approach, an open-coding method was applied to a subset of data, approximately 20% (5/25), or 5 complete prototypes, to identify the dominant themes among the prototypes. To ensure intercoder reliability, 2 research team members analyzed the same subset of data. RESULTS Overall, 9 dominant design requirements emerged from the qualitative analysis: customization, incentive motivation, social engagement, awareness, education, or recommendations, behavior tracking, location services, access to health professionals, data user agreements, and health assessment. This led to the development of a cross-platform app through an agile design process to collect standardized health surveys, narratives, geolocated pollution, weather, food desert exposure data, physical activity, social networks, and physiology through point-of-care devices. A Health Insurance Portability and Accountability Act–compliant cloud infrastructure was developed to collect, process, and review data, as well as generate alerts to allow automated signal processing and machine learning on the data to produce critical alerts. Integration with wearables and electronic health records via fast health care interoperability resources was implemented. CONCLUSIONS The MOYO mobile platform provides a comprehensive health and exposure monitoring system that allows for a broad range of compliance, from passive background monitoring to active self-reporting. These study findings support the notion that African Americans should be meaningfully involved in designing technologies that are developed to improve CVD outcomes in African American communities.

Certain migrant groups have been identified as being at increased risk of developing a psychotic disorder, but there is limited research on the outcomes for migrants who develop a first episode of psychosis (FEP). We investigated symptomatic outcomes (remission and relapse rates), functional outcomes (occupational status and relationships) and service utilization (hospital admission and engagement).Young people, aged between 15 and 24, who presented with FEP to the Early Psychosis Prevention and Intervention Centre (EPPIC) at Orygen between 01.01.11 and 31.12.16 were included. Place of birth was recorded at the time of presentation. To determine remission, symptoms were scored at three-month intervals using the short-form Scale for the Assessment of Positive Symptoms.A total of 1220 young people presented with FEP over the six-year period (mean age = 19.6 ± 2.8). Of these, 58.1% were male and 24.0% were first-generation migrants. While there was no difference in overall rates of admission after presentation, migrants were more likely to have an involuntary admission after presentation (31.4% vs. 24.6%, aHR = 1.54, 95% CI [1.19, 2.01]) and this risk was greatest for African migrants (HR = 1.98, 95% C.I. [1.37, 2.86]. The rates of remission and relapse were similar in migrants and those born in Australia and there was no difference in functional outcomes, such as employment rates at follow-up.The outcomes for migrants who experience FEP appear to be largely similar to those for the Australian-born population. Our finding that a greater rate of involuntary admission for migrants at presentation supports existing literature and needs further exploration to improve clinical care.

Although women remain underrepresented in U.S. elective office, female candidates have experienced similar or greater electoral success compared to their male counterparts. Research suggests both selection effects (the uniquely strong characteristics and qualifications of women who run for office) and selective candidacy (the decisions to run or not run for office based on the electoral context) contribute to this phenomenon. I leverage a large data set of candidate characteristics and electoral outcomes in state supreme court elections spanning 1990-2012 to clarify the causal mechanisms behind the electoral success of female candidates. I find that the success of female candidates in state supreme court elections is driven by the most capable women selectively running for open seats. I conclude that this phenomenon may be reflective of a broader gender gap in political ambition, with implications for tactics to improve gender representation in politics.

As the senior population in the United States increases, the aging LGBT (lesbian, gay, bisexual, transgender) population should also see comparable growth rates. Health care providers and social se...

Purpose The purpose of this paper is to present proposed solutions and interventions to some of the major barriers to providing adequate access to healthcare in Kenya. Specific business models are proposed to improve access to quality healthcare in low- and middle-income countries. Finally, strategies are developed for the retail clinic concept (RCC). Design/methodology/approach Google Scholar, PubMed and EBSCOhost were among the databases used to collect articles relevant to the purpose in Kenya. Various governmental and news articles were collected from Google searches. Relevant business models from other sectors were considered for potential application to healthcare and the retail clinic concept. Findings After a review of current methodologies and approaches to business and franchising models in various settings, the most relevant models are proposed as solutions to improving quality healthcare in Kenya through the RCC. For example, authors reviewed physician recruitment strategies, insurance plans and community engagement. The paper is informed by existing literature and reports as well as key informants. Research limitations/implications This paper lacks primary data collection within Kenya and is limited to a brief scoping review of literature. The findings provide effective strategies for various business and franchising models in healthcare. Originality/value The assembling of relevant information specific to Kenya and potential business models provides effective means of improving health delivery through business and franchising, focusing on innovative approaches and models that have proven effective in other settings.

Background Cardiovascular diseases (CVDs) are the leading cause of death worldwide and are increasingly affecting younger populations, particularly African Americans in the southern United States. Access to preventive and therapeutic services, biological factors, and social determinants of health (ie, structural racism, resource limitation, residential segregation, and discriminatory practices) all combine to exacerbate health inequities and their resultant disparities in morbidity and mortality. These factors manifest early in life and have been shown to impact health trajectories into adulthood. Early detection of and intervention in emerging risk offers the best hope for preventing race-based differences in adult diseases. However, young-adult populations are notoriously difficult to recruit and retain, often because of a lack of knowledge of personal risk and a low level of concern for long-term health outcomes. Objective This study aims to develop a system design for the MOYO mobile platform. Further, we seek to addresses the challenge of primordial prevention in a young, at-risk population (ie, Southern-urban African Americans). Methods Urban African Americans, aged 18 to 29 years (n=505), participated in a series of co-design sessions to develop MOYO prototypes (ie, HealthTech Events). During the sessions, participants were orientated to the issues of CVD risk health disparities and then tasked with wireframing prototype screens depicting app features that they considered desirable. All 297 prototype screens were subsequently analyzed using NVivo 12 (QSR International), a qualitative analysis software. Using the grounded theory approach, an open-coding method was applied to a subset of data, approximately 20% (5/25), or 5 complete prototypes, to identify the dominant themes among the prototypes. To ensure intercoder reliability, 2 research team members analyzed the same subset of data. Results Overall, 9 dominant design requirements emerged from the qualitative analysis: customization, incentive motivation, social engagement, awareness, education, or recommendations, behavior tracking, location services, access to health professionals, data user agreements, and health assessment. This led to the development of a cross-platform app through an agile design process to collect standardized health surveys, narratives, geolocated pollution, weather, food desert exposure data, physical activity, social networks, and physiology through point-of-care devices. A Health Insurance Portability and Accountability Act–compliant cloud infrastructure was developed to collect, process, and review data, as well as generate alerts to allow automated signal processing and machine learning on the data to produce critical alerts. Integration with wearables and electronic health records via fast health care interoperability resources was implemented. Conclusions The MOYO mobile platform provides a comprehensive health and exposure monitoring system that allows for a broad range of compliance, from passive background monitoring to active self-reporting. These study findings support the notion that African Americans should be meaningfully involved in designing technologies that are developed to improve CVD outcomes in African American communities.

Piezoelectric fans have attracted attentions in the past decades because of their low energy consumption, low noise level, light weight and reliability. A novel form of piezoelectric flapping fan is characterized experimentally and numerically. An experimental setup was built to measure the pressure and flow rate of piezoelectric fans with low static pressure at various frequencies. The fan performance curve was established. A high speed camera system was used to analyze the oscillation motion of the fan wings. The displacement of the leading edge and trailing edge of the piezoelectric fan wings are used as inputs to describe the deflection of the fan in the numerical model. The flow field obtained from the model is analyzed. The vortex shedding is observed and discussed. The pressure and flow rate obtained from the 2D numerical model are compared with the experimental results. The results provide a fundamental understanding of a piezoelectric fan with opposing oscillating wings.

This paper presents a novel piezoelectric flapping fan. The fan includes a bio-inspired thin wing attached to piezoelectric bending actuator supported through two connecting members. When activated by an AC signal, the piezoelectric actuator deflects up and down, inducing the wings to oscillate around their neutral position, generating a net air flow. The performance of the fan was characterized experimentally using a custom flow measurement system based on pressure difference and a high-speed camera. The cooling capability of the fan was also demonstrated with a fan-heatsink setup. The experimental results show this fan is capable of generating significant flow rate, thus making it a promising candidate for electronics cooling.

This chapter maps the landscape of health sciences librarian outreach to LGBTQ+ people. The authors develop this theme through case studies of health science librarians providing health information to the LGBTQ+ community and healthcare professionals. Following an overview of advocacy for LGBTQ+ health by the US National Network of Libraries of Medicine and professional information organizations, they conclude the chapter by discussing the “pioneering” nature of these projects and the common threads uniting them, and by identifying the next steps for continued successful outreach through the development of an evidence base and tailoring of outreach and resources to address other demographic aspects of the members of the LGBTQ+ community.

The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.

We monitored the effect of different gel aging temperatures (from −20 to 40 °C) and gel aging times (from 7 to 21 days) on the particle size and crystalline structure of template-free Linde type A zeolites through scanning electron microscopy, transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. We demonstrate the synthesis of zeolite LTA with average particle sizes of 0.45 ± 0.07 μm by preliminary heat treatment of the precursor gel at −8 °C followed by crystallization at 100 °C. Here, we found that aging the precursor gels for 2 weeks at 40 °C decreases the size of particles by 59% compared with particles formed from unaged gels, and aging gels for 2 weeks at −8 °C results in particles that have a 95% smaller diameter compared with particles formed from the unaged gel. We hypothesize that decreasing the precursor aging temperature below 0 °C leads to the occurrence of spinodal decomposition at which the nucleation barrier vanishes. Consequently, a very large number of nuclei form...

Clinical Practice Guidelines are succinct evidence-based recommendations and in psychiatry, exist to advise on psychotropic prescribing to effectively treat mental health conditions whilst minimising medication adverse effects. Implementation of psychiatric guidelines have, in the past, demonstrated little and transient impact on clinical practice. How effective prescribing guidelines are in aligning practice with evidence currently is unknown and this systematic review aimed to investigate said efficacy. Literature searches were performed on MEDLINE, EMBASE, and CINAHL up to September 2019 and articles were selected by two reviewers independently with discrepancies resolved by a third reviewer. The review identified 18 eligible articles pertaining to the following conditions: depressive disorders, psychotic disorders, post-traumatic stress disorder, anxiety disorders, bipolar affective disorder, attention deficit/hyperactivity disorder, borderline personality disorder, and opiate addiction with depression guidelines being the most frequently evaluated. Seven studies revealed guidelines effected no change in psychotropic prescribing. The remaining studies illustrated that even when practice was changed, the effect was generally small, emphasising the need to change guideline development and implementation, taking into account obstacles or opportunities specific to psychotropic pharmacotherapy.

Itch is relayed to higher centers by projection neurons in the spinal and medullary dorsal horn. We employed a double-label method to map the ascending projections of pruriceptive and nociceptive trigeminal and spinal neurons. The retrograde tracer fluorogold (FG) was stereotaxically injected into the right thalamus or lateral parabrachial area (LPb) in mice. Seven days later, mice received intradermal (id) microinjection of histamine, chloroquine, capsaicin, or vehicle into the left cheek. Histamine, chloroquine, and capsaicin intradermally elicited similar distributions of Fos-positive neurons in the medial aspect of the superficial medullary and spinal dorsal horn from the trigeminal subnucleus caudalis to C2. Among neurons retrogradely labeled from the thalamus, 43%, 8%, and 22% were Fos-positive following id histamine, chloroquine, or capsaicin. Among the Fos-positive neurons following pruritic or capsaicin stimuli, ∼1-2% were retrogradely labeled with FG. Trigeminoparabrachial projection neurons exhibited a higher incidence of double labeling in the superficial dorsal horn. Among the neurons retrogradely labeled from LPb, 36%, 29%, and 33% were Fos positive following id injection of histamine, chloroquine, and capsaicin, respectively. Among Fos-positive neurons elicited by id histamine, chloroquine, and capsaicin, respectively, 3.7%, 4.3%, and 4.1% were retrogradely labeled from LPb. The present results indicate that, overall, relatively small subpopulations of pruriceptive and/or nociceptive neurons innervating the cheek project to thalamus or LPb. These results imply that the vast majority of pruritogen- and algogen-responsive spinal neurons are likely to function as interneurons relaying information to projection neurons and/or participating in segmental nocifensive circuits.

We investigated roles for spinal neurons expressing the neurokinin-1 receptor (NK1R) and/or gastrin-releasing peptide receptor (GRPR) in a mouse model of ovalbumin (OVA)-induced chronic atopic dermatitis. Mice receiving repeated topical application of OVA exhibited atopic-like skin lesions and behavioral signs of chronic itch including spontaneous scratching, touch-evoked scratching (alloknesis), and enhancement of chloroquine-evoked scratching (hyperknesis). Substance P-saporin (SP-SAP) and bombesin-saporin (BB-SAP) were intrathecally injected into OVA-sensitized mice to neurotoxically ablate NK1R- or GRPR-expressing spinal neurons, respectively. SP-SAP diminished the expression of NK1R in the superficial spinal dorsal horn and significantly attenuated all behavioral signs of chronic itch. BB-SAP reduced the spinal dorsal horn expression of GRPR and significantly attenuated hyperknesis, with no effect on spontaneous scratching or alloknesis. To investigate whether NK1R-expressing spinal neurons project in ascending somatosensory pathways, we performed a double-label study. The retrograde tracer, Fluorogold (FG), was injected into either the somatosensory thalamus or lateral parabrachial nucleus. In the upper cervical (C1-2) spinal cord, most neurons retrogradely labeled with FG were located in the dorsomedial aspect of the superficial dorsal horn. Of FG-labeled spinal neurons, 89% to 94% were double labeled for NK1R. These results indicate that NK1R-expressing spinal neurons play a major role in the expression of symptoms of chronic itch and give rise to ascending somatosensory projections. Gastrin-releasing peptide receptor-expressing spinal neurons contribute to hyperknesis but not to alloknesis or ongoing itch. NK1R-expressing spinal neurons represent a potential target to treat chronic itch.

The sodium hydrogen exchanger isoform one (NHE1) plays a critical role coordinating asymmetric events at the leading edge of migrating cells and is regulated by a number of phosphorylation events influencing both the ion transport and cytoskeletal anchoring required for directed migration. Lysophosphatidic acid (LPA) activation of RhoA kinase (Rock) and the Ras-ERK growth factor pathway induces cytoskeletal reorganization, activates NHE1 and induces an increase in cell motility. We report that both Rock I and II stoichiometrically phosphorylate NHE1 at threonine 653 in vitro using mass spectrometry and reconstituted kinase assays. In fibroblasts expressing NHE1 alanine mutants for either Rock (T653A) or ribosomal S6 kinase (Rsk; S703A) we show that each site is partially responsible for the LPA-induced increase in transport activity while NHE1 phosphorylation by either Rock or Rsk at their respective site is sufficient for LPA stimulated stress fiber formation and migration. Furthermore, mutation of either T653 or S703 leads to a higher basal pH level and a significantly higher proliferation rate. Our results identify the direct phosphorylation of NHE1 by Rock and suggest that both RhoA and Ras pathways mediate NHE1-dependent ion transport and migration in fibroblasts.

Particle-reinforced metal matrix composites (pMMC) such as silicon carbide particle reinforced aluminum alloys (SiCp/Al) require special cutting tools due to the high hardness and abrasive properties of the ceramic particles. Diamond coated cutting tools are ideal for machining this type of pMMC. Previous research studies focus on the machinability of pMMCs with low ceramic content. The aim of this research is to determine the optimal cutting parameters for machining SiCp/Al material containing high silicon carbide particle reinforcement (>25%). Material removal rate (MRR) was used to determine the optimal cutting parameters with the tool wear and surface roughness as constraints. Cutting speed, feed rate, and depth of cut were used as design parameters for the design of experiment. High burr formation and cutting forces were observed during the experiments. Experimental milling tests are conducted using CVD diamond coated end mills and non-diamond tungsten carbide end mills. It was found that low tool rotation speeds, feed rates and depths of cut are necessary to achieve smoother surface finishes of Ra < 1 μm. A high MRR to low tool wear and surface roughness ratio was obtainable at a tool rotation speed of 6500 r/min, feed rate of 762 mm/min, and depth of cut of 3 mm. Results showed that a smooth surface roughness of the workpiece material was achieved with non-diamond tungsten carbide end mills, however, this was at the expense of extreme tool wear and high burr formation. An endurance test was run to test for complete tool failure.

In recent years, librarians in various sectors have been moving forward a conversation on the distinct information needs and information-seeking behavior of our lesbian, gay, bisexual, trans, and queer (LGBTQ) patrons and how well the profession recognizes and meets those needs. Health sciences librarianship has been slower than other areas of the profession in creating an evidence base covering the needs of its LGBTQ patrons, with, until recently, only very limited literature on this subject. LGBTQ health sciences librarianship is now starting to attract new interest, with librarians working together to bring this emerging specialization to the attention of the broader professional community. In this paper, the authors report on a dedicated panel discussion that took place at the 2016 joint annual meeting of the Medical Library Association and Canadian Health Libraries Association/Association des bibliothèques de la santé du Canada in Toronto, Ontario, Canada; discuss subsequent reflections; and highlight the emerging role for health sciences librarians in providing culturally competent services to the LGBTQ population. Recommendations are also provided for establishing a tool kit for LGBTQ health sciences librarianship from which librarians can draw. We conclude by highlighting the importance of critically reflective practice in health sciences librarianship in the context of LGBTQ health information.

BackgroundGlobally most neonatal deaths occur within the first week of life and in low-income and middle-income countries. Strengthening health system linkages for frontline providers—such as lay midwives providing home-based obstetrical care—may improve neonatal outcomes in these settings. Here, we conducted a quality improvement study to increase the detection of neonatal complications by lay midwives in rural Guatemala, thereby increasing referrals to a higher level of care.MethodsA quality improvement team in Guatemala reviewed drivers of neonatal health services provided by lay midwives. Improvement interventions included training on neonatal warning signs, optimised mobile health technology to standardise assessments and financial incentives for providers. The primary quality outcome was the rate of neonatal referral to a higher level of care.ResultsFrom September 2017 to September 2018, participating midwives attended 869 home deliveries and referred 80 neonates to a higher level of care. A proportion control chart, using the preintervention period from January to September 2017 as the baseline, showed an increase in the referral rate of all births from 1.5% to 9.9%. Special cause was obtained in January 2018 and sustained except for May 2018. The proportion of neonates receiving assessments by midwives in the first week of life increased to >90%. A trend toward an increasing number of days between neonatal deaths did not attain special cause.ConclusionsStructured improvement interventions, including mobile health decision support and financial incentives, significantly increased the detection of neonatal complications and referral of neonates to higher levels of care by lay midwives operating in rural home-based settings in Guatemala. The results show the value of improving the integration of lay midwives and other first responders into neonatal systems of care in low-resource settings.

To remedy the obscurity in perceptions linked with the Tiger mother phenomenon, and the dearth of research within immigrant-Asian subgroups, we attempted to provide an exploratory analysis on the parenting beliefs and practices of Vietnamese mothers. The voices of seven immigrant Vietnamese-Australian mothers from Western Australia were presented through Interpretive Phenomenological Analysis. The emergent themes revealed the development of a bi-cultural identity, education, respect, and parental control. Moreover, we found that many beliefs and practices hinge upon the cultural concepts of filial piety and Confucianism. Our findings also support the growing concern which suggest that parenting styles under Baumrind's (1971) typology are inaccurate for cross-cultural populations. Implications pertaining to culturally competent practice and directions for future research are discussed.

Genetically encodable sensors have been widely used in the detection of intracellular molecules ranging from metal ions and metabolites to nucleic acids and proteins. These biosensors are capable of monitoring in real-time the cellular levels, locations, and cell-to-cell variations of the target compounds in living systems. Traditionally, the majority of these sensors have been developed based on fluorescent proteins. As an exciting alternative, genetically encoded RNA-based molecular sensors (GERMS) have emerged over the past few years for the intracellular imaging and detection of various biological targets. In view of their ability for the general detection of a wide range of target analytes, and the modular and simple design principle, GERMS are becoming a popular choice for intracellular analysis. In this review, we summarize different design principles of GERMS based on various RNA recognition modules, transducer modules, and reporting systems. Some recent advances in the application of GERMS for intracellular imaging are also discussed. With further improvement in biostability, sensitivity, and robustness, GERMS can potentially be widely used in cell biology and biotechnology.

ObjectiveThe detection of aortoiliac occlusive disease (AIOD) has important clinical implications for patients with peripheral arterial disease. The clinical utility of the common femoral artery (C...

Management of vascular trauma has evolved tremendously since the turn of the 20(th) century. The lessons from each major military conflict over the past 100 years have refined our understanding of how to care for soldiers and civilians with vascular injuries. The recent wars in Iraq and Afghanistan have likewise improved our strategy for treating victims of vascular trauma. Understanding the principles that guide management of vascular injuries will result in preservation of life and limb.

Intelligent energy management control system (EMCS) in buildings offers an excellent means of reducing energy consumptions in heating, ventilation, and air-conditioning HVAC systems while maintaining or improving indoor environmental conditions. This can be achieved through the use of computational intelligence and optimization. The chapter thus proposes and evaluates a model-based optimization process for HVAC systems using evolutionary algorithm. The process can be integrated into the EMCS to perform several intelligent functions and achieve optimal whole-system performance. The proposed process addresses the requirements of the latest ASHRAE Standard 62.1. A whole building simulation energy software is used to generate the sub-hourly load. The simulations are performed to test the process and determine the potential energy savings achieved. The testing results demonstrate that total energy consumed by the HVAC system can be reduced by about 26 % when compared to the traditional operating strategies applied.

We conducted a study to biomechanically evaluate 3 methods of tibial-sided fixation for anterior cruciate ligament reconstruction: fully threaded interference screw only, interference screw backed with 4.75-mm SwiveLock anchor, and fully threaded bio-interference screw backed with 4.5-mm bicortical screw (all Arthrex). Thirty skeletally mature porcine tibiae were used. The first group was prepared by graft fixation within the tibial tunnel using only an interference screw. The second and third groups included an interference screw with 2 types of secondary fixation: 4.5-mm bicortical post and SwiveLock anchor. Mechanical testing consisted of 500 cycles between 50 and 250 N at 1 Hz, followed by a pull to failure conducted at 20 mm per minute. Ultimate load-to-failure testing demonstrated the largest mean (SD) load tolerated in the post/washer group, 1148 (186) N, versus the SwiveLock group, 1007 (176) N, and the screw-only group, 778 (139) N. There was no statistical difference between the 2 backup fixation groups. Use of a SwiveLock anchor as backup fixation at the tibial side in soft-tissue anterior cruciate ligament reconstruction is a safe, effective alternative to a bicortical post and provides statistically equivalent pullout strength with unlikely requirement for future hardware removal.

We report the identification and characterization of mouse matriptase-2 (m-matriptase-2), an 811-amino-acid protein composed of an N-terminal cytoplasmic domain, a membrane-spanning domain, two CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domains, three LDLR (low-density-lipoprotein receptor class A) domains and a C-terminal serine-protease domain. All m-matriptase-2 protein domain boundaries corresponded with intron/exon junctions of the encoding gene, which spans approx. 29 kb and comprises 18 exons. Matriptase-2 is highly conserved in human, mouse and rat, with the rat matriptase-2 gene (r-maltriptase-2) predicted to encode transmembrane and soluble isoforms. Western-blot analysis indicated that m-matriptase-2 migrates close to its theoretical molecular mass of 91 kDa, and immunofluorescence analysis was consistent with the proposed surface membrane localization of this protein. Reverse-transcription PCR and in-situ-hybridization analysis indicated that m-matriptase-2 expression overlaps with the distribution of mouse hepsin (m-hepsin, a cell-surface serine protease identified in hepatoma cells) in adult tissues and during embryonic development. In adult tissues both are expressed at highest levels in liver, kidney and uterus. During embryogenesis m-matriptase-2 expression peaked between days 12.5 and 15.5. m-hepsin expression was biphasic, with peaks at day 7.5 to 8.5 and again between days 12.5 and 15.5. In situ hybridization of embryonic tissues indicated abundant expression of both m-matriptase-2 and m-hepsin in the developing liver and at lower levels in developing pharyngo–tympanic tubes. While m-hepsin was detected in the residual embryonic yolk sac and with lower intensity in lung, heart, gastrointestinal tract, developing kidney tubules and epithelium of the oral cavity, m-matriptase-2 was absent in these tissues, but strongly expressed within the nasal cavity by olfactory epithelial cells. Mechanistic insight into the potential role of this new transmembrane serine protease is provided by its novel expression profile in embryonic and adult mouse.

This article reviews a study of five leading journals of the field of conflict resolution and peace. It tabulates the importance of five elements in all articles appearing in these journals from 1990–2000. It finds that most articles address theory and practice, less address research, and a very small proportion are concerned with ethics or service. The study shows that this pattern largely is independent of the gender or intellectual base of the authors. Further, the study shows little change over the years. It concludes that the field systematically has neglected the impact of our thinking and work on those in conflict and suggests that we will imperil the further development of our field if we continue in this way.