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Abstract In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936–0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843–0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862–0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR.

Background Rilonacept, a once‐weekly interleukin‐1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin‐1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long‐term extension further explored recurrent pericarditis natural history and treatment duration decision‐making during 24 additional months of open‐label rilonacept treatment. Methods and Results Seventy‐four patients commenced the long‐term extension, with a median (maximum) total rilonacept duration of 22 (35) months. Individually, 18 months after the most proximal pericarditis recurrence, investigators decided to continue rilonacept on study, suspend rilonacept for off‐treatment observation (rescue allowed), or discontinue the study. The annualized incidence of pericarditis recurrence on rilonacept up to the 18‐month decision milestone was 0.04 events/patient‐year versus 4.4 events/patient‐year prestudy while on oral therapies. At the 18‐month decision milestone, 64% (33/52) continued rilonacept, 15% (8/52) suspended rilonacept for observation, and 21% (11/52) discontinued the study. Among the 33 patients (1/33; 3.0%) continuing rilonacept (median time to recurrence could not be estimated due to too few events), a single recurrence occurred 4 weeks after a treatment interruption. Among patients suspending rilonacept, 75% (6/8) experienced recurrence (median time to recurrence, 11.8 weeks [95% CI, 3.7 weeks to not estimable]). There was a 98% reduction in risk of pericarditis recurrence among patients continuing rilonacept treatment after the 18‐month decision milestone versus those suspending treatment for observation (hazard ratio, 0.02; P

Coronary ischemia is uncommon in patients in their third decade of life. We present a 21-year-old woman with classic exertional angina secondary to a large cardiac paraganglioma. Cardiac paragangliomas are rare extra-adrenal neuroendocrine tumors that arise from chromaffin cells. Cardiac symptoms can be related to catecholamine excess or anatomical compression.

Abstract Remote monitoring is beneficial for the management of patients with cardiovascular implantable electronic devices by impacting morbidity and mortality. With increasing numbers of patients using remote monitoring, keeping up with higher volume of remote monitoring transmissions creates challenges for device clinic staff. This international multidisciplinary document is intended to guide cardiac electrophysiologists, allied professionals, and hospital administrators in managing remote monitoring clinics. This includes guidance for remote monitoring clinic staffing, appropriate clinic workflows, patient education, and alert management. This expert consensus statement also addresses other topics such as communication of transmission results, use of third‐party resources, manufacturer responsibilities, and programming concerns. The goal is to provide evidence‐based recommendations impacting all aspects of remote monitoring services. Gaps in current knowledge and guidance for future research directions are also identified.

Abstract Background People living with HIV (PLWH) are at increased risk of developing Chronic Obstructive Pulmonary Disease (COPD) independent of cigarette smoking. We hypothesized that dysbiosis in PLWH is associated with epigenetic and transcriptomic disruptions in the airway epithelium. Methods Airway epithelial brushings were collected from 18 COPD + HIV + , 16 COPD − HIV + , 22 COPD + HIV − and 20 COPD – HIV − subjects. The microbiome, methylome, and transcriptome were profiled using 16S sequencing, Illumina Infinium Methylation EPIC chip, and RNA sequencing, respectively. Multi ‘omic integration was performed using Data Integration Analysis for Biomarker discovery using Latent cOmponents. A correlation > 0.7 was used to identify key interactions between the ’omes. Results The COPD + HIV −, COPD −HIV + , and COPD + HIV + groups had reduced Shannon Diversity (p = 0.004, p = 0.023, and p = 5.5e−06, respectively) compared to individuals with neither COPD nor HIV, with the COPD + HIV + group demonstrating the most reduced diversity. Microbial communities were significantly different between the four groups (p = 0.001). Multi ‘omic integration identified correlations between Bacteroidetes Prevotella, genes FUZ, FASTKD3, and ACVR1B, and epigenetic features CpG-FUZ and CpG-PHLDB3. Conclusion PLWH with COPD manifest decreased diversity and altered microbial communities in their airway epithelial microbiome. The reduction in Prevotella in this group was linked with epigenetic and transcriptomic disruptions in host genes including FUZ, FASTKD3, and ACVR1B.

Telerehabilitation and robotics, either traditional rigid or soft, have been extensively studied and used to improve hand functionality after a stroke. However, a limited number of devices combined these two technologies to such a level of maturity that was possible to use them at the patients’ home, unsupervised. Here we present a novel investigation that demonstrates the feasibility of a system that integrates a soft inflatable robotic glove, a cloud-connected software interface, and a telerehabilitation therapy. Ten chronic moderate-to-severe stroke survivors independently used the system at their home for 4 weeks, following a software-led therapy and being in touch with occupational therapists. Data from the therapy, including automatic assessments by the robot, were available to the occupational therapists in real-time, thanks to the cloud-connected capability of the system. The participants used the system intensively (about five times more movements per session than the standard care) for a total of more than 8 hr of therapy on average. We were able to observe improvements in standard clinical metrics (FMA +3.9 ± 4.0, p

Prognosis of metastatic triple negative breast cancer (mTNBC) remains poor despite recent advances in therapeutic options. Trastuzumab deruxtecan (T-DXd) has shown promising efficacy in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, which is defined by immunohistochemistry (IHC) 1+ or 2+ and lack of HER2 amplification by fluorescence in situ hybridization (FISH) testing. The purpose of the study is to evaluate the safety and initial evidence of efficacy of intratumoral administration of CF33-hNIS-anti-PD-L1 (CHECKvacc) against mTNBC. Oncolytic virus CHECKvacc intratumoral injection is currently undergoing investigation in patients with mTNBC as a single agent (NCT05081492). The patient was enrolled on the clinical trial CHECKvacc for the Treatment of Metastatic Triple Negative Breast Cancer , received a single dose of CHECKvacc, and discontinued the study due to lack of immediate response. We report a case of a patient with mTNBC who was heavily pretreated and presented with extensive dermal metastasis. Two dermal metastasis biopsies in 2021 showed HER2 0 by IHC. The patient received a single dose of CHECKvacc and discontinued the study due to lack of immediate response. Twenty-five days later, the patient received treatment with T-DXd, and her tumor regressed significantly. The patient’s disease-free survival was 10 months (December 2021–October 2022). The sequential treatment with intratumoral injection of CHECKvacc followed by T-DXd may have significant clinical activity in select patients with heavily pretreated mTNBC. ClinicalTrials.gov NCT05081492.

We describe a case of a 47-year-old patient who presented with severe lactic acidosis, troponinemia, and acute kidney injury after receiving 8 mg of intramuscular dexamethasone for seasonal allergies in the setting of an undiagnosed epinephrine-secreting pheochromocytoma. This case was atypical, however, in that the patient exhibited only mildly elevated noninvasive measured blood pressures. Following a period of alpha-adrenergic blockade, the tumor was resected successfully. Steroid administration can precipitate pheochromocytoma crisis that may present unusually as in our patient with mild hypertension but profound lactic acidosis.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health‐related quality of life. RHAPSODY (rilonacept inhibition of interleukin‐1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL‐1α and ‐β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient‐reported outcome questionnaire score change during the trial. Methods and Results Participants completed 5 patient‐reported outcome (PRO) questionnaires assessing pericarditis pain, health‐related quality of life, general health status, sleep impact, and overall symptom severity. PRO score changes during the treatment run‐in period (12 weeks) and the blinded randomized withdrawal period (up to 24 weeks) were evaluated using descriptive statistics and mixed model repeated measures analyses. Participants with PRO data from the run‐in period (n=84) and the randomized withdrawal period (n=61; 30 rilonacept, 31 placebo) were included in analyses. Run‐in baseline PRO scores indicated that pericarditis symptoms during pericarditis recurrence impacted health‐related quality of life. All PRO scores significantly improved (P

Summary: Background: Age-related comorbidities such as chronic obstructive pulmonary disease (COPD) are common in people living with human immunodeficiency virus (PLWH). We investigated the relationship between COPD and the epigenetic age of the airway epithelium and peripheral blood of PLWH. Methods: Airway epithelial brushings from 34 PLWH enrolled in the St. Paul's Hospital HIV Bronchoscopy cohort and peripheral blood from 378 PLWH enrolled in The Strategic Timing of Antiretroviral Treatment (START) study were profiled for DNA methylation. The DNA methylation biomarker of age and healthspan, GrimAge, was calculated in both tissue compartments. We tested the association of GrimAge with COPD in the airway epithelium and airflow obstruction as defined by an FEV1/FVC

Abstract Background Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β cytokine trap) to treat RP. Methods Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience. The Phase 2 trial enrolled participants with active symptomatic RP (A-RP, n = 16) and corticosteroid-dependent participants with no active recurrence at baseline (CSD-RP, n = 9). All participants received rilonacept weekly during a 6-week base treatment period (TP) plus an optional 18-week extension period (EP). Tapering of concomitant medications, including corticosteroids (CS), was permitted during EP. HRQoL was assessed using the PROMIS GH, and patient-reported pain and blood levels of c-reactive protein (CRP) were collected at Baseline and follow-up periods. A secondary, descriptive analysis of the Phase 2 trial efficacy results was completed using HRQoL measures to characterize both the impact of RP and the treatment effect of rilonacept. Results Information from qualitative interviews demonstrated that PROMIS GH concepts are relevant to adults with RP. From the Phase 2 trial, both participant groups showed impacted HRQoL at Baseline (mean PROMIS Global Physical Health [GPH] and Global Mental Health [GMH], were lower than population norm average). In A-RP, GPH/MPH improved by end of base TP and were sustained through EP (similar trends were observed for pain and CRP). Similarly, in CSD-RP, GPH/MPH improved by end of TP and further improved during EP, during CS tapering or discontinuation, without disease recurrence (low pain scores and CRP levels continued during the TP and EP). Conclusion This is the first study demonstrating impaired HRQoL in RP. Rilonacept treatment was associated with HRQoL improvements using PROMIS GH scores. Maintained/improved HRQoL during tapering/withdrawal of CS without recurrence suggests that rilonacept may provide an alternative to CS. Trial registration: ClinicalTrials.Gov; NCT03980522; 5 June 2019, retrospectively registered; https://clinicaltrials.gov/ct2/show/NCT03980522 .

Liu et al study the molecular and structural mechanism of the modulation of ASIC1 channel gating using functional, crystallographic, computational and mutational approaches. They identify small molecules that allosterically stabilize the closed state by binding at the acidic pocket of the channel.

BackgroundDepression and anxiety create a large health burden and increase the risk of premature mortality. Mental health screening is vital, but more sophisticated screening and monitoring methods are needed. The Ellipsis Health App addresses this need by using semantic information from recorded speech to screen for depression and anxiety.ObjectivesThe primary aim of this study is to determine the feasibility of collecting weekly voice samples for mental health screening. Additionally, we aim to demonstrate portability and improved performance of Ellipsis’ machine learning models for patients of various ages.MethodsStudy participants were current patients at Desert Oasis Healthcare, mean age 63 years (SD = 10.3). Two non-randomized cohorts participated: one with a documented history of depression within 24 months prior to the study (Group Positive), and the other without depression (Group Negative). Participants recorded 5-min voice samples weekly for 6 weeks via the Ellipsis Health App. They also completed PHQ-8 and GAD-7 questionnaires to assess for depression and anxiety, respectively.ResultsProtocol completion rate was 61% for both groups. Use beyond protocol was 27% for Group Positive and 9% for Group Negative. The Ellipsis Health App showed an AUC of 0.82 for the combined groups when compared to the PHQ-8 and GAD-7 with a threshold score of 10. Performance was high for senior participants as well as younger age ranges. Additionally, many participants spoke longer than the required 5 min.ConclusionThe Ellipsis Health App demonstrated feasibility in using voice recordings to screen for depression and anxiety among various age groups and the machine learning models using Transformer methodology maintain performance and improve over LSTM methodology when applied to the study population.

We report the case of a 54-year-old woman who presented for cardiological evaluation having noted a decline in her heart rate on her wearable heart rate monitor. She was found to be in 2:1 atrioventricular block. Subsequent evaluation revealed cardiac and pulmonary sarcoidosis, treated with steroids and implantable cardioverter-defibrillator placement. (Level of Difficulty: Beginner.)

X-linked adrenoleukodystrophy (ALD) is a peroxisomal metabolic disorder with a highly complex clinical presentation. ALD is caused by mutations in the ABCD1 gene, and is characterized by the accumulation of very long-chain fatty acids in plasma and tissues. Disease-causing mutations are ‘loss of function’ mutations, with no prognostic value with respect to the clinical outcome of an individual. All male patients with ALD develop spinal cord disease and a peripheral neuropathy in adulthood, although age of onset is highly variable. However, the lifetime prevalence to develop progressive white matter lesions, termed cerebral ALD (CALD), is only about 60%. Early identification of transition to CALD is critical since it can be halted by allogeneic hematopoietic stem cell therapy only in an early stage. The primary goal of this study is to identify molecular markers which may be prognostic of cerebral demyelination from a simple blood sample, with the hope that blood-based assays can replace the current protocols for diagnosis. We collected six well-characterized brother pairs affected by ALD and discordant for the presence of CALD and performed multi-omic profiling of blood samples including genome, epigenome, transcriptome, metabolome/lipidome, and proteome profiling. In our analysis we identify discordant genomic alleles present across all families as well as differentially abundant molecular features across the omics technologies. The analysis was focused on univariate modeling to discriminate the two phenotypic groups, but was unable to identify statistically significant candidate molecular markers. Our study highlights the issues caused by a large amount of inter-individual variation, and supports the emerging hypothesis that cerebral demyelination is a complex mix of environmental factors and/or heterogeneous genomic alleles. We confirm previous observations about the role of immune response, specifically auto-immunity and the potential role of PFN1 protein overabundance in CALD in a subset of the families. We envision our methodology as well as dataset has utility to the field for reproducing previous or enabling future modifier investigations.

Background Obesity and obstructive sleep apnea (OSA) are associated with atrial fibrillation (AF), yet these conditions remain inadequately treated. We report on the feasibility and efficacy of a nurse‐led risk factor modification program utilizing a pragmatic approach to address obesity and OSA in AF patients. Methods and Results AF patients with obesity (body mass index ≥30 kg/m2) and/or the need for OSA management (high risk per Berlin Questionnaire or untreated OSA) were voluntarily enrolled for risk factor modification, which comprised patient education, lifestyle modification, coordination with specialists, and longitudinal management. Weight loss and OSA treatment were monitored by monthly follow‐up calls and/or continuous positive airway pressure (CPAP) unit downloads. Quality of life and arrhythmia symptoms were assessed with the SF‐36 and AF Severity Scale at baseline and at 6 months. From November 1, 2016 to October 31, 2017, 252 patients (age 63±11 years; 71% male; 57% paroxysmal AF) were enrolled, 189 for obesity and 93 for OSA. Obese patients who enrolled lost significantly greater percent body weight than those who declined (3% versus 0.3%; P

Human pressure on ecosystems is among the major drivers of biodiversity loss. As biodiversity plays a key role in supporting the human enterprise, its decline puts the well-being of human societies at risk. Halting biodiversity loss is therefore a key policy priority, as reflected in the 2020 Aichi Biodiversity Targets under strategic goal A. The Ecological Footprint has become a widely used metric for natural capital and ecosystem accounting, and is frequently cited in the sustainability debate, where it is often used for tracking human-induced pressures on ecosystems and biodiversity. Given its potential role as an indirect metric for biodiversity-related policies, this paper breaks down the Ecological Footprint into its components and analyzes resource and ecosystem service flows at an international level. We discuss its usefulness in tracking the underlying drivers of habitat impacts and biodiversity loss. We find that: China is a major net importer of all biomass biocapacity components; the largest net exporters of forest biocapacity are not low-income countries; a very high proportion of the Ecological Footprint of fishing grounds is traded internationally; Singapore and at least three Middle East countries are almost wholly reliant on net imports for the cropland biocapacity they consume.

Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular clock dating of ancestors. Times to most recent common ancestors (tMRCAs) could be robustly estimated only for the more recently diverged subtypes; the tMRCA of the ID/IAB/IC/II and IE clades of VEE virus (VEEV) were estimated at ca. 149-973 years ago. Evolution of the IE subtype has been characterized by a significant evolutionary shift from the rest of the VEEV complex, with an increase in structural protein substitutions that are unique to this group, possibly reflecting adaptation to its unique enzootic mosquito vector Culex (Melanoconion) taeniopus. Our inferred tree topologies suggest that VEEV is maintained primarily in situ, with only occasional spread to neighboring countries, probably reflecting the limited mobility of rodent hosts and mosquito vectors.

To identify if the absence of the vasoactive intestinal peptide (VIP) gene enhances susceptibility to death from metastatic bladder cancer, two strains of mice were injected with MB49 murine bladder cancer cells. The growth and spread of the cancer was measured over a period of 4 weeks in C57BL/6 mice and 5 weeks in VIP knockout (KO) mice. A Kaplan–Meier plot was constructed to compare control C57BL/6 mice and C57BL/6 mice with MB49 vs. VIP KO controls and VIP KO mice with MB49. The wild-type (WT) strain (C57BL/6) contained the VIP gene, while the other strain, VIP knockout backcrossed to C57BL/6 (VIP KO) did not and was thus unable to endogenously produce VIP. VIP KO mice had increased mortality compared to C57BL/6 mice at 4 weeks. The number of ulcers between both groups was not statistically significant. In vitro studies indicated that the presence VIP in high doses reduced MB49 cell growth, as well as macrophage inhibitory factor (MIF), a growth factor in bladder cancer cells. These findings support the concept that VIP may attenuate susceptibility to death from bladder cancer, and that it exerts its effect via downregulation of MIF.

The UN’s Sustainable development Goals (SDGs) are the most significant global effort so far to advance global sustainable development. Bertelsmann Stiftung and the sustainable development solutions network released an SDG index to assess countries’ average performance on SDGs. Ranking high on the SDG index strongly correlates with high per person demand on nature (or “Footprints”), and low ranking with low Footprints, making evident that the SDGs as expressed today vastly underperform on sustainability. Such underperformance is anti-poor because lowest-income people exposed to resource insecurity will lack the financial means to shield themselves from the consequences. Given the significance of the SDGs for guiding development, rigorous accounting is essential for making them consistent with the goals of sustainable development: thriving within the means of planet Earth.

Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors. We report here the development of a high affinity (KD = 200 nM) inhibitor from a low affinity fragment hit with supporting biochemical and structural data showing these molecules bind to the cGAS active site. We also report a new high throughput cGAS fluorescence polarization (FP)-based assay to enable the rapid identification and optimization of cGAS inhibitors. This FP assay uses Cy5-labelled cGAMP in combination with a novel high affinity monoclonal antibody that specifically recognizes cGAMP with no cross reactivity to cAMP, cGMP, ATP, or GTP. Given its role in the innate immune response, cGAS is a promising therapeutic target for autoinflammatory disease. Our results demonstrate its druggability, provide a high affinity tool compound, and establish a high throughput assay for the identification of next generation cGAS inhibitors.

Pseudomonas aeruginosa is an opportunistic pathogen that rarely causes pneumonia in otherwise healthy patients. We describe a case of community-acquired P. aeruginosa pneumonia in a previously healthy individual who likely acquired the infection from a home humidifier.

Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the Americas.

Ecological Footprint accounting quantifies the supply and demand of Earth’s biocapacity. The National Footprint Accounts (NFA) are the most widely used Ecological Footprint (EF) dataset, and provide results for most countries and the world from 1961 to 2014, based primarily on publicly available UN datasets. Here, we review the evolution of the NFA, describe and quantify the effects of improvements that have been implemented into the accounts since the 2012 edition, and review the latest global trends. Comparing results over six editions of NFAs, we find that time-series trends in world results remain stable, and that the world Ecological Footprint for the latest common year (2008) has increased six percent after four major accounting improvements and more than thirty minor improvements. The latest results from the NFA 2018 Edition for the year 2014 indicate that humanity’s Ecological Footprint is 1.7 Earths, and that global ecological overshoot continues to grow. While improved management practices and increased agricultural yields have assisted in a steady increase of Earth’s biocapacity since 1961, humanity’s Ecological Footprint continues to increase at a faster pace than global biocapacity, particularly in Asia, where the total and per capita Ecological Footprint are increasing faster than all other regions.

The increasing rate of urbanization along with its socio-environmental impact are major global challenges. Therefore, there is a need to assess the boundaries to growth for the future development of cities by the inclusion of the assessment of the environmental carrying capacity (ECC) into spatial management. The purpose is to assess the resource dependence of a given entity. ECC is usually assessed based on indicators such as the ecological footprint (EF) and biocapacity (BC). EF is a measure of the biologically productive areas demanded by human consumption and waste production. Such areas include the space needed for regenerating food and fibers as well as sequestering the generated pollution, particularly CO2 from the combustion of fossil fuels. BC reflects the biological regeneration potential of a given area to regenerate resources as well to absorb waste. The city level EF assessment has been applied to urban zones across the world, however, there is a noticeable lack of urban EF assessments in Central Eastern Europe. Therefore, the current research is a first estimate of the EF and BC for the city of Wrocław, Poland. This study estimates the Ecological Footprint of Food (EFF) through both a top-down assessment and a hybrid top-down/bottom-up assessment. Thus, this research verifies also if results from hybrid method could be comparable with top-down approach. The bottom-up component of the hybrid analysis calculated the carbon footprint of food using the life cycle assessment (LCA) method. The top-down result of Wrocław’s EFF were 1% greater than the hybrid EFF result, 0.974 and 0.963 gha per person respectively. The result indicated that the EFF exceeded the BC of the city of Wrocław 10-fold. Such assessment support efforts to increase resource efficiency and decrease the risk associated with resources—including food security. Therefore, there is a need to verify if a city is able to satisfy the resource needs of its inhabitants while maintaining the natural capital on which they depend intact.

As part of an ongoing programme to study Sp(2N) gauge theories as potential realisations of composite Higgs models, we consider the case of Sp(4) on the lattice, both as a pure gauge theory, and with two Dirac fermion flavors in the fundamental representation. In order to compare results between these two cases and maintain control of lattice artefacts, we make use of the gradient flow to set the scale of the simulations. We present some technical aspects of the simulations, including preliminary results for the scale setting in the two cases and results for the topological charge history.

Tensor Network methods have been established as a powerful technique for simulating low dimensional strongly-correlated systems for over two decades. Employing the formalism of Matrix Product States, we investigate the phase diagram of the massive Thirring model. We also show the possibility of studying soliton dynamics and topological phase transition via the Thirring model.

As a first step in the study of Sp(2N) composite Higgs models, we obtained a set of novel numerical results for the pure gauge Sp(4) lattice theory in 3+1 space-time dimensions. Results for the continuum extrapolations of the string tension and the glueball mass spectrum are presented and their values are compared with the same quantities in neighbouring SU(N) models.

As a first step towards a quantitative understanding of the SU(4)/Sp(4) composite Higgs model through lattice calculations, we discuss the low energy effective field theory resulting from the SU(4) → Sp(4) global symmetry breaking pattern. We then consider an Sp(4) gauge theory with two Dirac fermion flavours in the fundamental representation on a lattice, which provides a concrete example of the microscopic realisation of the SU(4)/Sp(4) composite Higgs model. For this system, we outline a programme of numerical simulations aiming at the determination of the low-energy constants of the effective field theory and we test the method on the quenched theory. We also report early results from dynamical simulations, focussing on the phase structure of the lattice theory and a calculation of the lowest-lying meson spectrum at coarse lattice spacing.

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.

Recent technical advances in the field of quantitative proteomics have stimulated a large number of biomarker discovery studies of various diseases, providing avenues for new treatments and diagnostics. However, inherent challenges have limited the successful translation of candidate biomarkers into clinical use, thus highlighting the need for a robust analytical methodology to transition from biomarker discovery to clinical implementation. We have developed an end-to-end computational proteomic pipeline for biomarkers studies. At the discovery stage, the pipeline emphasizes different aspects of experimental design, appropriate statistical methodologies, and quality assessment of results. At the validation stage, the pipeline focuses on the migration of the results to a platform appropriate for external validation, and the development of a classifier score based on corroborated protein biomarkers. At the last stage towards clinical implementation, the main aims are to develop and validate an assay suitable for clinical deployment, and to calibrate the biomarker classifier using the developed assay. The proposed pipeline was applied to a biomarker study in cardiac transplantation aimed at developing a minimally invasive clinical test to monitor acute rejection. Starting with an untargeted screening of the human plasma proteome, five candidate biomarker proteins were identified. Rejection-regulated proteins reflect cellular and humoral immune responses, acute phase inflammatory pathways, and lipid metabolism biological processes. A multiplex multiple reaction monitoring mass-spectrometry (MRM-MS) assay was developed for the five candidate biomarkers and validated by enzyme-linked immune-sorbent (ELISA) and immunonephelometric assays (INA). A classifier score based on corroborated proteins demonstrated that the developed MRM-MS assay provides an appropriate methodology for an external validation, which is still in progress. Plasma proteomic biomarkers of acute cardiac rejection may offer a relevant post-transplant monitoring tool to effectively guide clinical care. The proposed computational pipeline is highly applicable to a wide range of biomarker proteomic studies.

Context Syncope is a commonly encountered by primary care physicians and cardiologists. Etiology is frequently not apparent, and patients may undergo unnecessary tests. Treatment must be tailored to the likely etiology. Complexities of diagnosis and treatment often warrant referral to a specialist. Objective To highlight the evolving recommendations for managing syncope in a clinically and cost effective manner. Evidence Acquisition An electronic literature search was undertaken of the Medline database from January 1996 to April 2006, using the Medical Subject Heading syncope, defibrillators, pacemakers, echocardiogram, cardiomyopathy, long QT syndrome, Arrhythmogenic right ventricular dysplasia , and Brugada syndrome. Abstracts and titles were reviewed to identify English-language trials. Bibliographies from the references as well as scientific statements from the Heart Rhythm Society, American Heart Association, and American College of Cardiology were reviewed. Evidence Synthesis A methodical approach to syncope can improve diagnosis, limit testing, and identify patients at risk of fatal outcome. A thorough history, physical exam and electrocardiogram are critical to the initial diagnosis. Presence of heart disease determines the extent of work-up and treatment. A trans-thoracic echocardiogram should be performed in patients with an unclear diagnosis and a positive cardiac history or an abnormal ECG. Ventricular arrhythmias are the most common cause of syncope in patients with structural heart disease. Patients with an ejection fraction less than 30 percent should receive an implantable defibrillator with few exceptions. An electrophysiology study may assist risk stratification in syncopal patients with borderline ventricular function. In patients without structural heart disease, the presence of a well defined arrhythmia syndrome consistent with a genetically determined risk of sudden death must be sought. The 12-lead electrocardiogram, family history and clinical presentation will identify most high-risk patients. Patients without structural heart disease can often be managed conservatively with well defined strategies for preventing neurocardiogenic syncope. Conclusions Managing syncope requires a methodical approach. An understanding of the limitations of the diagnostic tools and treatments is important. Lethal causes of syncope make it imperative to recognize the appropriate timing of referring patients to specialists.