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Introduction: A right-sided aortic arch is a rare congenital cardiovascular anomaly that arises from persistence of the right fourth aortic arch and regression of the left fourth aortic arch. This variation commonly gives rise to an aberrant left subclavian artery (ALSA). In this report, we present an unusual variation of a right-sided aortic arch with an isolated common subclavian trunk (CST). Methods: During a routine dissection of a female cadaver, a right-sided aortic arch variation with an aberrant left subclavian artery was observed. The thorax was further dissected to reveal the right-sided aortic arch and anomalous origin of the ALSA from a CST. Results: The ascending aorta arose from the heart to form a right-sided aortic arch which branched into 1) a CST, 2) a left common carotid artery, and 3) a right common carotid artery. The CST branched into a right subclavian artery and an ALSA which traversed posteriorly to the esophagus to its normal anatomical position. The descending thoracic aorta passed along the right lateral aspect of the vertebral column, traversed posteriorly to the esophagus, and continued descending in its anatomical position through the aortic hiatus. Conclusion: Rare aortic arch congenital anomalies such as a common subclavian trunk predispose the body to numerous clinical complications. A common subclavian trunk can cause cardiovascular complications and gastrointestinal complications due to compression of the esophagus. A deep understanding of the variations in the aortic arch and its branches is necessary for all physicians when managing patients with cardiovascular and upper gastrointestinal symptoms.

Abstract Resistance mechanisms to immune checkpoint blockade therapy (ICBT) limit its response duration and magnitude. Paradoxically, Interferon γ (IFNγ), a key cytokine for cellular immunity, can promote ICBT resistance. Using syngeneic mouse tumour models, we confirm that chronic IFNγ exposure confers resistance to immunotherapy targeting PD-1 (α-PD-1) in immunocompetent female mice. We observe upregulation of poly-ADP ribosyl polymerase 14 (PARP14) in chronic IFNγ-treated cancer cell models, in patient melanoma with elevated IFNG expression, and in melanoma cell cultures from ICBT-progressing lesions characterised by elevated IFNγ signalling. Effector T cell infiltration is enhanced in tumours derived from cells pre-treated with IFNγ in immunocompetent female mice when PARP14 is pharmacologically inhibited or knocked down, while the presence of regulatory T cells is decreased, leading to restoration of α-PD-1 sensitivity. Finally, we determine that tumours which spontaneously relapse in immunocompetent female mice following α-PD-1 therapy upregulate IFNγ signalling and can also be re-sensitised upon receiving PARP14 inhibitor treatment, establishing PARP14 as an actionable target to reverse IFNγ-driven ICBT resistance.

Background: Variations in the roots of the brachial plexus and their branches may cause unexpected complications during surgical procedures of the neck. In this report, we show an extremely rare variation of the long thoracic nerve. Methods: During routine dissection of the posterior triangle of the neck in a white female cadaver, a variation in a branch of the brachial plexus was observed and documented. Further dissection of the axilla and anterolateral thoracic wall were performed to follow the course of the anomalous superficial nerve. Results: The abnormal nerve was discovered to be a variation of the long thoracic nerve (LTN) formed from a supraclavicular union of only the C6 and C7 spinal nerve roots. Conclusions: Variations in the anatomy of the brachial plexus are not uncommon, but variations of the LTN are rare. Awareness of the LTN in relation to the brachial plexus is useful for the head and neck surgeon operating in less often encountered spaces to prevent injury.

Recruitment of Receptor Tyrosine Kinase signalling partners during endocytosis, specifically during recycling to the plasma membrane, is crucial to signal propagation and regulation. Here, the authors reveal FGFR signalling partners proximal to recycling endosomes with a spatially resolved phosphoproteomics approach.

IMPORTANCE:. Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes. OBJECTIVES:. The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices. DESIGN, SETTING, AND PARTICIPANTS:. This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning. MAIN OUTCOMES AND MEASURES:. Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams. RESULTS:. Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes. CONCLUSIONS AND RELEVANCE:. Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care.

Purpose: To report and describe multiple rare variations of the gluteal vasculature that were discovered during dissection. Methods: During a routine dissection of a cadaver in the gluteal region, the gluteus maximus muscle was reflected bilaterally and variations in the gluteal vasculature were discovered. In the pelvic cavity, the branches of the internal iliac arteries were exposed to reveal variations in the origins of these arteries. Results: On the left side of the gluteal region, the superficial branch of the superior gluteal artery was large and descended inferiorly across the piriformis muscle. The inferior gluteal artery was unusually small and with few branches. The internal pudendal artery gave off several branches with one of these branches contributing to the cruciate anastomosis. On the right side, an enlarged superficial branch of the superior gluteal artery descended over the piriformis muscle into the inferior half of the gluteal region and the inferior gluteal artery was completely absent. Conclusions: Gluteal flaps used in the reconstruction of trunk wounds and pressure sores utilize the knowledge that both the superior and inferior gluteal arteries supply the local musculature of this region. In cases where a gluteal artery may be absent, like in the current study, lifting a flap based on one artery may lead to necrosis of adjacent musculature due to the loss of its blood supply. Knowledge of these types of anomalies may prompt surgeons to proceed with more caution during surgical interventions in the gluteal region.

Cutaneous melanoma is one of the most aggressive human malignancies and shows increasing incidence. Mast cells (MCs), long-lived tissue-resident cells that are particularly abundant in human skin where they regulate both innate and adaptive immunity, are associated with melanoma stroma (MAMCs). Thus, MAMCs could impact melanoma development, progression, and metastasis by secreting proteases, pro-angiogenic factors, and both pro-inflammatory and immuno-inhibitory mediators. To interrogate the as-yet poorly characterized role of human MAMCs, we have purified MCs from melanoma skin biopsies and performed RNA-seq analysis. Here, we demonstrate that MAMCs display a unique transcriptome signature defined by the downregulation of the FcεRI signaling pathway, a distinct expression pattern of proteases and pro-angiogenic factors, and a profound upregulation of complement component C3. Furthermore, in melanoma tissue, we observe a significantly increased number of C3+ MCs in stage IV melanoma. Moreover, in patients, C3 expression significantly correlates with the MC-specific marker TPSAB1, and the high expression of both markers is linked with poorer melanoma survival. In vitro, we show that melanoma cell supernatants and tumor microenvironment (TME) mediators such as TGF-β, IL-33, and IL-1β induce some of the changes found in MAMCs and significantly modulate C3 expression and activity in MCs. Taken together, these data suggest that melanoma-secreted cytokines such as TGF-β and IL-1β contribute to the melanoma microenvironment by upregulating C3 expression in MAMCs, thus inducing an MC phenotype switch that negatively impacts melanoma prognosis.

Increasing evidence indicates that success of targeted therapies in the treatment of cancer is context-dependent and is influenced by a complex crosstalk between signaling pathways and between cell types in the tumor. The Fibroblast Growth Factor (FGF)/FGF receptor (FGFR) signaling axis highlights the importance of such context-dependent signaling in cancer. Aberrant FGFR signaling has been characterized in almost all cancer types, most commonly non-small cell lung cancer (NSCLC), breast cancer, glioblastoma, prostate cancer and gastrointestinal cancer. This occurs primarily through amplification and over-expression of FGFR1 and FGFR2 resulting in ligand-independent activation. Mutations and translocations of FGFR1-4 are also identified in cancer. Canonical FGF-FGFR signaling is tightly regulated by ligand-receptor combinations as well as direct interactions with the FGFR coreceptors heparan sulfate proteoglycans (HSPGs) and Klotho. Noncanonical FGFR signaling partners have been implicated in differential regulation of FGFR signaling. FGFR directly interacts with cell adhesion molecules (CAMs) and extracellular matrix (ECM) proteins, contributing to invasive and migratory properties of cancer cells, whereas interactions with other receptor tyrosine kinases (RTKs) regulate angiogenic, resistance to therapy, and metastatic potential of cancer cells. The diversity in FGFR signaling partners supports a role for FGFR signaling in cancer, independent of genetic aberration.

The extracellular signal-regulated protein kinase 5 (ERK5) is a non-redundant mitogen-activated protein kinase (MAPK) that exhibits a unique C-terminal extension which comprises distinct structural and functional properties. Here, we sought to elucidate the significance of phosphoacceptor sites in the C-terminal transactivation domain of ERK5. We have found that Thr732 acted as a functional gatekeeper residue controlling C-terminal-mediated nuclear translocation and transcriptional enhancement. Consistently, using a non-bias quantitative mass spectrometry approach, we demonstrated that phosphorylation at Thr732 conferred selectivity for binding interactions of ERK5 with proteins related to chromatin and RNA biology, whereas a number of metabolic regulators were associated with full-length wild type ERK5. Additionally, our proteomic analysis revealed that phosphorylation of the Ser730-Glu-Thr732-Pro motif could occur independently of dual phosphorylation at Thr218-Glu-Tyr220 in the activation loop. Collectively, our results firmly establish the significance of C-terminal phosphorylation in regulating ERK5 function. The post-translational modification of ERK5 on its C-terminal tail might be of particular relevance in cancer cells where ERK5 has be found to be hyperphosphoryated.

Boron nitride nanotubes (BNNTS) have only been shown to dissolve in chlorosulfonic acid (CSA) at low concentrations. Here the authors successfully demonstrate the formation of liquid crystals of BNNTs in CSA that can be used to produce macroscopically aligned neat fibers of BNNTs.

The upper cervical spine not only consists of intricate bony and ligamentous anatomy affording unique flexibility but also has increased susceptibility to injuries. The upper cervical spine trauma can result in a wide spectrum of injuries that can be managed both operatively and nonoperatively. Several existing classification systems have been proposed to describe injuries of the upper cervical spine, many of which rely on anatomic descriptions of injury location. Prior fracture classifications are limited in scope, characterizing fractures restricted to a single region of the upper cervical spine, and fail to provide insight into injury management. The AO Spine Upper Cervical Injury Classification System (AO Spine UCCS) has recently been developed as a comprehensive, yet concise classification scheme to describe all injuries of the upper cervical spine. The AO Spine UCCS represents a significant development in the classification of upper cervical spine injuries, with the potential to serve as a decision-making instrument to aid in patient management.

The pandemic caused by the SARS-CoV-2 virus (COVID-19) has significantly affected the tourism industry. Tourist destinations have adopted emergency measures and restrictions that have affected the mobility of individuals around the world. This study aims to analyze the effects of the COVID-19 pandemic on the tourism industry in Malaysia and its overall economic performance. This research used an extensive set of statistical tests, including a newly constructed Auto-Regressive Neural Network-ADF (ARNN-ADF) test, to determine if foreign visitor arrivals from 10 main source markets in Malaysia will revert to normal. Secondary data from various government published sources were used in this conceptual methodology technique for this study. Based on the research results and exploratory research of the literature, we listed in a synthesizing manner several measures to ensure the resilience of the tourism sector during the COVID-19 pandemic period. This research makes a significant contribution to the literature in terms of validating a new framework that emphasizes the effects of tourists that are largely transitory. In conclusion, this conceptual study will further help the authorities to take precautions and the best policy to be implemented in the future. Doi: 10.28991/esj-2021-SPER-10 Full Text: PDF

Summary: In honey bee colonies, workers generally change tasks with age (from brood care, to nest work, to foraging). While these trends are well established, our understanding of how individuals distribute tasks during a day, and how individuals differ in their lifetime behavioral trajectories, is limited. Here, we use automated tracking to obtain long-term data on 4,100+ bees tracked continuously at 3 Hz, across an entire summer, and use behavioral metrics to compare behavior at different timescales. Considering single days, we describe how bees differ in space use, detection, and movement. Analyzing the behavior exhibited across their entire lives, we find consistent inter-individual differences in the movement characteristics of individuals. Bees also differ in how quickly they transition through behavioral space to ultimately become foragers, with fast-transitioning bees living the shortest lives. Our analysis framework provides a quantitative approach to describe individual behavioral variation within a colony from single days to entire lifetimes.

Abstract The monofunctional platinum(II) complex, phenanthriplatin, acts by blocking transcription, but its regulatory effects on long-noncoding RNAs (lncRNAs) have not been elucidated relative to traditional platinum-based chemotherapeutics, e.g., cisplatin. Here, we treated A549 non-small cell lung cancer and IMR90 lung fibroblast cells for 24 h with either cisplatin, phenanthriplatin or a solvent control, and then performed microarray analysis to identify regulated lncRNAs. RNA22 v2 microRNA software was subsequently used to identify microRNAs (miRNAs) that might be suppressed by the most regulated lncRNAs. We found that miR-25-5p, -30a-3p, -138-5p, -149-3p, -185-5p, -378j, -608, -650, -708-5p, -1253, -1254, -4458, and -4516, were predicted to target the cisplatin upregulated lncRNAs, IMMP2L-1, CBR3-1 and ATAD2B-5, and the phenanthriplatin downregulated lncRNAs, AGO2-1, COX7A1-2 and SLC26A3-1. Then, we used qRT-PCR to measure the expression of miR-25-5p, -378j, -4516 (A549) and miR-149-3p, -608, and -4458 (IMR90) to identify distinct signaling effects associated with cisplatin and phenanthriplatin. The signaling pathways associated with these miRNAs suggests that phenanthriplatin may modulate Wnt/β-catenin and TGF-β signaling through the MAPK/ERK and PTEN/AKT pathways differently than cisplatin. Further, as some of these miRNAs may be subject to dissimilar lncRNA targeting in A549 and IMR90 cells, the monofunctional complex may not cause toxicity in normal lung compared to cancer cells by acting through distinct lncRNA and miRNA networks.

Honey bee workers take on different tasks for the colony as they age. Here, the authors develop a method to extract a descriptor of the individuals’ social networks and show that interaction patterns predict task allocation and distinguish different developmental trajectories.

Objectives: The size of one's support network is positively related to health and well-being. It is therefore important to understand this association in people with Type 1 diabetes, as this could inform interventions. Moreover, the type of support (emotional, instrumental, informational) offered likely varies by gender of both the person seeking support and offering support. We thus examine the relationship between the composition of (perceived) social support networks and well-being in a sample of 121 persons with Type 1 diabetes. Design: An egocentric social network survey, combined with survey measures. Main outcome(s): The size and composition of support networks and well-being. Measures: Participants indicated the type of support individuals in their contact network offered and their gender, alongside measures of perceived social support and well-being. They indicated which individuals offered which types of support (emotional, instrumental, informational). Results: Perceived support was associated with the actual size of the emotional support network. Further, the size of the emotional support network was associated with well-being. Using multilevel models we examined assortment by gender in social support networks. Compared to women, men were more inclined to list the opposite gender as support, especially for emotional and informational support. Conclusion: Mapping out an individual's multidimensional support network paints a more complete picture of support than single item measures of support. We therefore recommend relying on a social network methodology to gain a more complete understanding of support networks. The findings highlight that an association exists between emotional network size and wellbeing. Given the potential implications of this finding for the quality of life of diabetes patients, it is important to establish the causality of this relationship.

Background. Pre–lung transplant (LTx) gastroesophageal reflux (GER) and circulating antibodies against the lung self-antigens (SAbs) collagen V and K-alpha-1 tubulin may predispose recipients to chronic lung allograft dysfunction (CLAD). We aimed to study the association of pre-LTx GER or pre-LTx SAbs with CLAD. Methods. In this retrospective analysis of patients who underwent LTx between 2015 and 2019, pre-LTx GER and SAbs were dichotomously defined as present or absent. The study group comprised recipients with either GER‚ SAbs, or both, and the control group comprised recipients without GER or SAbs. Endpoints included CLAD and survival. Results. Ninety-five LTx recipients were divided into a study group (n = 71; 75%) and a control group (n = 24; 25%). Pretransplant GER was associated with pre-LTx SAbs (odds ratio [95% confidence intervals], 5.022 [1.419-17.770]; P = 0.012). In addition, the study group (either GER‚ SAbs, or both) had a higher risk of CLAD (hazard ratio [95% confidence intervals], 8.787 [1.694-45.567]; P = 0.010) and lower CLAD-free survival after LTx than the control group (P = 0.007); however, overall survival was similar between the 2 groups (P = 0.618). Conclusions. GER was associated with elevated SAbs in LTx candidates, and either GER, SAbs, or both were associated with CLAD in LTx recipients. This association suggests that GER may cause an immune response to normally sequestered lung-associated self-antigens that drives ongoing lung injury.

Abstract Background Self-assembly of the amyloid-β (Aβ) peptide into aggregates, from small oligomers to amyloid fibrils, is fundamentally linked with Alzheimer’s disease (AD). However, it is clear that not all forms of Aβ are equally harmful and that linking a specific aggregate to toxicity also depends on the assays and model systems used (Haass et al., J Biol. Chem 269:17741–17748, 1994; Borchelt et al., Neuron 17:1005–1013, 1996). Though a central postulate of the amyloid cascade hypothesis, there remain many gaps in our understanding regarding the links between Aβ deposition and neurodegeneration. Methods In this study, we examined familial mutations of Aβ that increase aggregation and oligomerization, E22G and ΔE22, and induce cerebral amyloid angiopathy, E22Q and D23N. We also investigated synthetic mutations that stabilize dimerization, S26C, and a phospho-mimetic, S8E, and non-phospho-mimetic, S8A. To that end, we utilized BRI2-Aβ fusion technology and rAAV2/1-based somatic brain transgenesis in mice to selectively express individual mutant Aβ species in vivo. In parallel, we generated PhiC31-based transgenic Drosophila melanogaster expressing wild-type (WT) and Aβ40 and Aβ42 mutants, fused to the Argos signal peptide to assess the extent of Aβ42-induced toxicity as well as to interrogate the combined effect of different Aβ40 and Aβ42 species. Results When expressed in the mouse brain for 6 months, Aβ42 E22G, Aβ42 E22Q/D23N, and Aβ42WT formed amyloid aggregates consisting of some diffuse material as well as cored plaques, whereas other mutants formed predominantly diffuse amyloid deposits. Moreover, while Aβ40WT showed no distinctive phenotype, Aβ40 E22G and E22Q/D23N formed unique aggregates that accumulated in mouse brains. This is the first evidence that mutant Aβ40 overexpression leads to deposition under certain conditions. Interestingly, we found that mutant Aβ42 E22G, E22Q, and S26C, but not Aβ40, were toxic to the eye of Drosophila. In contrast, flies expressing a copy of Aβ40 (WT or mutants), in addition to Aβ42WT, showed improved phenotypes, suggesting possible protective qualities for Aβ40. Conclusions These studies suggest that while some Aβ40 mutants form unique amyloid aggregates in mouse brains, they do not exacerbate Aβ42 toxicity in Drosophila, which highlights the significance of using different systems for a better understanding of AD pathogenicity and more accurate screening for new potential therapies.

Abstract Background The extension of the interdialytic interval due to due to dialysis session non-attendance varies according to which session of the week the patient misses. The impact of this on subsequent hospitalization and mortality is unknown. Methods The ARO cohort study prospectively collected data from hemodialysis patients across 15 European countries on demography, comorbidity, laboratory, hospitalisation, mortality and individual hemodialysis sessions from 2007 to 2014. Event rates for death and hospitalisation according to dialysis day of the week were calculated for patients who attended the three previous scheduled hemodialysis sessions, who then on the next scheduled dialysis day either attended or did not attend. The hazard ratio for these events following non-attendance for the first compared to the second dialysis session of the week was estimated using Cox proportional hazards model adjusted for patient demographics. Results 3.8 million hemodialysis sessions in 9397 patients were analysed. The non-attendance rates for Monday/Wednesday/Friday sessions were 0.8, 0.9% & 1.4% respectively, and for Tuesday/Thursday/Saturday sessions were 0.6, 1.0% & 1.2% respectively. Compared to those who attended, for the 48–72 h between non-attendance and the next scheduled haemodialysis session, mortality significantly increased from 4.86 to 51.9/100 pt-yrs and hospitalisation increased from 0.58 to 2.1/yr. As time from the two-day break increased, the risk associated with non-attendance lessened: compared to missing the second hemodialysis session, missing the first session had a hazard ratio for mortality of 2.04 (95% CI 1.27–3.29), and for hospitalisation 1.78 (95% CI 1.29–2.47). In patients who attended their scheduled dialysis session and the three preceding, after the two-day break there were absolute increases in mortality (8.3 vs. 4.9/100 pt-yrs) and hospitalisation (1.0 vs. 0.6/yr for the rest of the week) comparable to previous studies. Conclusions In addition to hospitalisation and mortality increases seen after the two-day break, additional harm may be manifested in the greater increases in mortality and hospitalisation observed after non-attendance for the first hemodialysis session after the two-day break compared to missing other sessions.

Background. Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, complications, and treatment of persistent OH in 13 LTx recipients. Methods. We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results. Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m2, respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR

The objective of this study is to develop a skeleton model for assessing active marrow dose from bone-seeking beta-emitting radionuclides. This article explains the modeling methodology which accounts for individual variability of the macro- and microstructure of bone tissue. Bone sites with active hematopoiesis are assessed by dividing them into small segments described by simple geometric shapes. Spongiosa, which fills the segments, is modeled as an isotropic three-dimensional grid (framework) of rod-like trabeculae that "run through" the bone marrow. Randomized multiple framework deformations are simulated by changing the positions of the grid nodes and the thickness of the rods. Model grid parameters are selected in accordance with the parameters of spongiosa microstructures taken from the published papers. Stochastic modeling of radiation transport in heterogeneous media simulating the distribution of bone tissue and marrow in each of the segments is performed by Monte Carlo methods. Model output for the human femur at different ages is provided as an example. The uncertainty of dosimetric characteristics associated with individual variability of bone structure was evaluated. An advantage of this methodology for the calculation of doses absorbed in the marrow from bone-seeking radionuclides is that it does not require additional studies of autopsy material. The biokinetic model results will be used in the future to calculate individual doses to members of a cohort exposed to 89,90Sr from liquid radioactive waste discharged to the Techa River by the Mayak Production Association in 1949-1956. Further study of these unique cohorts provides an opportunity to gain more in-depth knowledge about the effects of chronic radiation on the hematopoietic system. In addition, the proposed model can be used to assess the doses to active marrow under any other scenarios of 90Sr and 89Sr intake to humans.

In 2006, the National Health Service commenced with assuming responsibility for the delivery and commissioning of mental healthcare services in prisons within the UK. Previous research has indicated that some prison environments may present challenges to the delivery of mental healthcare for prison populations. The present study aimed to explore the experiences of staff working in NHS offender health teams to identify the sources of adversity that frontline staff may encounter when providing mental healthcare in prison settings. The present study also aimed to identify working conditions that may be conducive in facilitating the delivery of mental healthcare in prison settings. Mental healthcare professionals (n = 10) who worked in NHS offender health teams took part in 1:1 semi-structured interviews that were audio recorded and transcribed verbatim. The thematic analysis of the dataset indicated three themes that presented sources of adversity for NHS offender health teams in their delivery of mental health care in prisons; which were 1) location of mental healthcare delivery 2) communication links with stakeholders and 3) prison policies, procedures and legislation. The results of this study have illustrated some of the work-related factors that require attention in order to further support frontline staff in their delivery of mental healthcare in prison settings.

In recent decades researchers in a variety of disciplines have developed a new "urban science," the central goal of which is to build general theory regarding the social processes underlying urbanization. Much work in urban science is animated by the notion that cities are complex systems. What does it mean to make this claim? Here we adopt the view that complex systems entail both variation and structure, and that their properties vary with system size and with respect to where and how they are measured. Given this, a general framework regarding the social processes behind urbanization needs to account for empirical regularities that are common to both contemporary cities and past settlements known through archaeology and history. Only by adopting an explicitly historical perspective can such fundamental structure be revealed. The identification of shared properties in past and present systems has been facilitated by research traditions that define cities (and settlements more broadly) as networks of social interaction embedded in physical space. Settlement Scaling Theory (SST) builds from these insights to generate predictions regarding how measurable properties of cities and settlements are related to their population size. Here, we focus on relationships between population and area across past settlement systems and present-day world cities. We show that both patterns and variations in these measures are explicable in terms of SST, and that the framework identifies baseline infrastructural area as an important system-level property of urban systems that warrants further study. We also show that predictive theory is helpful even in cases where the data do not conform to model predictions.

Despite recent technological advances in seafloor mapping systems, the resulting products and the overall operational efficiency of surveys are often affected by poor awareness of the oceanographic environment in which the surveys are conducted. Increasingly reliable ocean nowcast and forecast model predictions of key environmental variables – from local to global scales – are publicly available, but they are often not used by ocean mappers. With the intention of rectifying this situation, this work evaluates some possible ocean mapping applications for commonly available oceanographic predictions by focusing on one of the available regional models: NOAA’s Gulf of Maine Operational Forecast System. The study explores two main use cases: the use of predicted oceanographic variability in the water column to enhance and extend (or even substitute) the data collected on-site by sound speed profilers during survey data acquisition; and, the uncertainty estimation of oceanographic variability as a meaningful input to estimate the optimal time between sound speed casts. After having described the techniques adopted for each use case and their implementation as an extension of publicly available ocean mapping tools, this work provides evidence that the adoption of these techniques has the potential to improve efficiency in survey operations as well as the quality of the resulting ocean mapping products.

The revelation in May 2015 of the shipment of γ irradiation–inactivated wild-type Bacillus anthracis spore preparations containing a small number of live spores raised concern about the safety and security of these materials. The finding also raised doubts about the validity of the protocols and procedures used to prepare them. Such inactivated reference materials were used as positive controls in assays to detect suspected B. anthracis in samples because live agent cannot be shipped for use in field settings, in improvement of currently deployed detection methods or development of new methods, or for quality assurance and training activities. Hence, risk-mitigated B. anthracis strains are needed to fulfill these requirements. We constructed a genetically inactivated or attenuated strain containing relevant molecular assay targets and tested to compare assay performance using this strain to the historical data obtained using irradiation-inactivated virulent spores.

Switchgrass (Panicum virgatum L.), as a model herbaceous crop species for bioenergy production, is targeted to improve biomass yield and feedstock quality. Plant height is a major component contributing to biomass yield. Accordingly, the objectives of this research were to analyze phenotypic variation for biomass and plant height and the association between them and to localize associated plant height QTLs. Two lowland switchgrass mapping populations, one selfed and another hybrid population established in the field at Perkins and Stillwater, Oklahoma, were deployed in the experiment for two years post establishment. Large genetic variation existed for plant biomass and height within the two populations. Plant height was positively correlated with biomass yield in the selfed population (r = 0.39, P

In order to understand psychobiological responses to stress it is necessary to observe how people react to controlled stressors. A range of stressors exist for this purpose; however, laboratory stressors that are representative of real life situations provide more ecologically valid opportunities for assessing stress responding. The current study assessed psychobiological responses to an ecologically valid laboratory stressor involving multitasking and critical evaluation. The stressor elicited significant increases in psychological and cardiovascular stress reactivity; however, no cortisol reactivity was observed. Other socially evaluative laboratory stressors that lead to cortisol reactivity typically require a participant to perform tasks that involve verbal responses, whilst standing in front of evaluative others. The current protocol contained critical evaluation of cognitive performance; however, this was delivered from behind a seated participant. The salience of social evaluation may therefore be related to the response format of the task and the method of evaluation. That is, the current protocol did not involve the additional vulnerability associated with in person, face-to-face contact, and verbal delivery. Critical evaluation of multitasking provides an ecologically valid technique for inducing laboratory stress and provides an alternative tool for assessing psychological and cardiovascular reactivity. Future studies could additionally use this paradigm to investigate those components of social evaluation necessary for eliciting a cortisol response. Keywords: Multitasking, Critical social evaluation, Stress reactivity, Ecological validity

Abstract Background Left ventricular outflow tract velocity time integral (LVOT VTI) is a measure of cardiac systolic function and cardiac output. Heart failure patients with low cardiac output are known to have poor cardiovascular outcomes. Thus, extremely low LVOT VTI may predict heart failure patients at highest risk for mortality. Methods Patients with heart failure and extremely low LVOT VTI were identified from a single-center database. Baseline characteristics and heart failure related clinical outcomes (death, LVAD) were obtained at 12 months. Correlation between clinical endpoints and the following variables were analyzed: ejection fraction (EF), pulmonary artery systolic pressure (PASP), NYHA class, renal function, Doppler cardiac output (CO), and LVOT VTI. Results Study cohort consisted of 100 patients. At the 12-month follow up period, 30 events (28 deaths, 2 LVADs) were identified. Occurrence of death and LVAD implantation was statistically associated with a lower LVOT VTI (p = 0.039) but not EF (p = 0.169) or CO (p = 0.217). In multivariate analysis, LVOT VTI (p = 0.003) remained statistically significant, other significant variables were age (p = 0.033) and PASP (p = 0.022). Survival analysis by LVOT VTI tertile demonstrated an unadjusted hazard ratio of 4.755 (CI 1.576-14.348, p = 0.006) for combined LVAD and mortality at one year. Conclusions Extremely low LVOT VTI strongly predicts adverse outcomes and identifies patients who may benefit most from advanced heart failure therapies.

Abstract Background Rare conditions can be catastrophic for families and the implications for public health can be substantial. Our study compared basic surveillance through active medical record review with a linked administrative data file to assess the number of cases of two rare conditions, fragile X syndrome (FXS) and muscular dystrophy (MD) in a population. Methods Two methods of data collection were used to collect information from five counties comprising two standard metropolitan statistical areas of South Carolina. The passive system relied mostly on health claims data using ICD-9 CM diagnostic codes. The active system relied on a nurse abstracting records from a list of all licensed physicians with specialties in neurology, orthopedics, and genetics. Results There were 141 FXS cases and 348 MD cases that met the case definitions using active surveillance. Additional cases were found for both conditions but they were determined to not be true cases. After linking the actively collected MD and FXS cases to passive datasets, we found that the estimated total numbers of cases were similar to using capture-recapture analysis; the positive predictive values for cases identified in the passive system were 56.6% for MD and 75.7% for FXS. Conclusions Applying capture-recapture methods to passively collected surveillance data for rare health conditions produced an estimate of the number of true cases that was similar to that obtained through active data collection.

This autoethnographic case study examines the experience of managers with hiring student paraprofessionals into various roles within peer-to-peer education models and programmes as a method to increase the diversity in learning development services in the Canadian context. Tailoring learning development through peer-to-peer education models for diverse student groups is an important aspect of how learning development supports students in higher education. Including the knowledge and perspectives of student paraprofessionals who better reflect the diversity of the population we serve has been an important aspect of our practice. Our purpose for this case study is to better understand how our experiences with paraprofessional staff diversity, over a seven-year period (2010-2017), have influenced our practice of learning development in an institutional context focussed on creating a more inclusive and welcoming environment on campus to better support the needs of diverse learners. The knowledge that we gained through this analysis of diversity and peer learning as an approach to learning development may serve as an example of the value of autoethnography as a method to provide useful insight to professionals and leaders in the field.

Background Simulation plays a key role in assessing performance in Advanced Cardiovascular Life Support (ACLS). Traditional knowledge tests are also important for assessing the cognitive elements of ACLS performance. However, the association between the two has not been established. In this study, we focus on one important element in ACLS—interpretation of electrocardiograms (ECG)—and the potential of knowledge tests to serve as predictors of improvement in ACLS performance. Methods We looked at the correlation between Mexican medical students’ improvement in ECG interpretation performance in ACLS megacode simulations (from the start of the semester to the end of the semester), and their scores on ECG interpretation knowledge tests. Results We found significant improvement in ECG interpretation in ACLS megacode simulation (from pre-semester to post-semester), but this was not predicted by the ECG interpretation knowledge test scores. The correlation was .079 (p = 0.66). Conclusions These results suggest that even cognitive tasks such as ECG interpretation can be expressed and assessed differently in simulation versus traditional knowledge testing.

Background: Low-level, chronic viral infections have been suspect in the development of select autoimmune diseases, including primary Sjögren’s syndrome (pSS). Multiple studies have shown stimulation of antiviral response pathways in pSS tissues suggestive of a viral infection. Yet, with this data in hand, a causal link between a viral infection and development of pSS had not been identified. Therefore, a study was designed to further define the viral landscape within pSS-affected salivary gland tissue to identify potential viral-mediated triggers in the pathogenesis of this autoimmune disease. Methods: A viral microarray was utilized to measure viral transcripts present in salivary gland tissue from patients diagnosed with pSS compared to healthy controls. Murine models of salivary gland localized HDV antigen expression were developed to evaluate the capacity of a chronic HDV signature to trigger the development of a pSS-like phenotype. Results: Through this analysis, two distinct viral profiles were identified, including the increased presence of hepatitis delta virus (HDV) in 50% of pSS patients evaluated. Presence of HDV antigen and sequence were confirmed in minor salivary gland tissue. Patients with elevated HDV levels in salivary gland tissue were negative for detectible hepatitis B virus (HBV) surface antigen and antibodies to HBV or HDV. Expression of HDV antigens in vivo resulted in reduced stimulated saliva flow, increase in focal lymphocytic infiltrates, and development of autoantibodies. Conclusion: Identification of HDV in pSS patients and induction of a complete pSS-like phenotype in vivo provides further support of a viral-mediated etiopathology in the development of pSS.

Congenital mesoblastic nephroma (CMN) is a rare renal tumor of infancy. Here, we present a case of CMN presenting in a 29 week premature male in a twin gestation. An abdominal mass had been noted on prenatal ultrasound. He was initially treated with right radical nephrectomy. Pathology was consistent with cellular type CMN. Three months postoperatively, the patient developed pulmonary metastasis and underwent wedge resection of the right lung lesion. He subsequently underwent adjuvant chemotherapy, to which he has responded well. We discuss the presentation and management of patients with CMN and address the indications for postoperative chemotherapy.

According to Milliken and Shaw (2012) a surge in illegal rhino poaching in South Africa since 2006 was linked to increasing demand for rhino horn in Vietnam. This article examines one of the key frames, the ‘Voodoo Wildlife Parts’ (VWP) frame, which Environmental Non-Government Organisations (ENGOs) in Vietnam have been using in rhino horn demand reduction media campaigns. The VWP frame emerged from the findings of a research project that investigated the news frames present in the media outputs of seven ENGOs, both local and international, opposing the Illegal Wildlife Trade (IWT) in Vietnam. This article will briefly outline the four frames that emerged from that research, then discuss the two subthemes of the VWP frame and its scientific basis and the nature of the feedback from journalists and the public that influenced the frame’s production.