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Tube thoracostomy (TT) in trauma is lifesaving. A previous audit at Counties Manukau District Health Board (CMDHB), New Zealand, showed a 22% complication rate for trauma TT. Subsequently CMDHB introduced a procedural guideline to reduce complications. The Health and Disability Commission published a report concerning oversights in TT removal. This led us to evaluate complications, documentation and procedural monitoring to identify ways to improve patient safety.A 30-month retrospective audit of patients presenting to CMDHB, with injuries which may require TT. Those who had a TT in situ, did not require a TT or whose presentation was not secondary to trauma were excluded.One hundred and forty-three TTs were performed in one hundred and fifteen patients. About 87% had injuries secondary to blunt mechanism. Penetrating injuries were more likely to require TT (P = 0.015). Non-accidental injuries were more likely to need TT (P = 0.025). The complication rate was 25.2%. TT prior to imaging had a 31% complication rate (P 0.03). About 23% had no TT insertion note. 40% had no TT removal note. About 9% TT insertions had no tertiary information to identify the proceduralist and a complication rate of 46%. About 22% of insertions and 4% of removals documented consent. About 2% of insertions documented anticoagulation status. Interventional radiology had the best documentation of data points assessed (P 0.0001). Post-procedural monitoring recommendations were documented in 1% insertions and 11% removals.The complication rate has not reduced despite introduction of a guideline. Procedural documentation and monitoring were inadequate, potentially impacting patient safety.

Bottlenose dolphins ( Tursiops truncatus and Tursiops aduncus; BND) live in coastal waters, prompting frequent contact with humans. Interaction with BND can be either planned (e.g. swim-with-dolphin experiences) or chance (e.g. BND surfing on boat wakes). These charismatic cetaceans are common in many forms of wildlife tourism, including marine wildlife tours, swim-with-dolphin experiences and hand feeding. BND also interact with humans by chance during ocean recreation activities, such as surfing, swimming and boating. Within fisheries, there is both cooperation and conflict between humans and BND. Through a literature review, this paper highlights the effects such interactions cause to both BND and humans with a focus on wildlife tourism, ocean recreation and fisheries.

The first European Vasculitis Society (EUVAS) meeting report was published in 2017. Herein, we report on developments in the past 5 years which were greatly influenced by the pandemic. The adaptability to engage virtually, at this critical time in society, embodies the importance of networks and underscores the role of global collaborations. We outline state-of-the-art webinar topics, updates on developments in the last 5 years, and proposals for agendas going forward. A host of newly reported clinical trials is shaping practice on steroid minimization, maintenance strategies, and the role of newer therapies. To guide longer-term strategies, a longitudinal 10-year study investigating relapse, comorbidity, malignancy, and survival rates is at an advanced stage. Disease assessment studies are refining classification criteria to differentiate forms of vasculitis more fully. A large international validation study on the histologic classification of anti-neutrophil cytoplasmic antibody (ANCA) glomerulonephritis, recruiting new multicenter sites and comparing results with the Kidney Risk Score, has been conducted. Eosinophilic granulomatosis with polyangiitis (EGPA) genomics offers potential pathogenic subset and therapeutic insights. Among biomarkers, ANCA testing is favoring immunoassay as the preferred method for diagnostic evaluation. Consolidated development of European registries is progressing with an integrated framework to analyze large clinical data sets on an unprecedented scale.

We consider the problem of solving large-scale linear least squares problems that have one or more linear constraints that must be satisfied exactly. While some classical approaches are theoretically well founded, they can face difficulties when the matrix of constraints contains dense rows or if an algorithmic transformation used in the solution process results in a modified problem that is much denser than the original one. We propose modifications with an emphasis on requiring that the constraints be satisfied with a small residual. We examine combining the null-space method with our recently developed algorithm for computing a null-space basis matrix for a “wide” matrix. We further show that a direct elimination approach enhanced by careful pivoting can be effective in transforming the problem to an unconstrained sparse-dense least squares problem that can be solved with existing direct or iterative methods. We also present a number of solution variants that employ an augmented system formulation, which can be attractive for solving a sequence of related problems. Numerical experiments on problems coming from practical applications are used throughout to demonstrate the effectiveness of the different approaches.

Avoiding end-stage kidney disease in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) has a high therapeutic priority. Although renal response is a crucial measure to capture clinically relevant changes, clinal trials have used various definitions and no well-studied key surrogate markers to predict renal outcome in AAV exist. Differences in clinical features and histopathologic and therapeutic approaches will influence the course of kidney function. Its assessment through traditional surrogates (i.e. serum creatinine, glomerular filtration rate, proteinuria, hematuria and disease activity scores) has limitations. Refinement of these markers and the incorporation of novel approaches such as the assessment of histopathological changes using cutting-edge molecular and machine learning mechanisms or new biomarkers could significantly improve prognostication. The timing is favourable since large datasets of trials conducted in AAV are available and provide a valuable resource to establish renal surrogate markers and, likely, aim to investigate optimized and tailored treatment approaches according to a renal response score. In this review we discuss important points missed in the assessment of kidney function in patients with AAV and point towards the importance of defining renal response and clinically important short- and long-term predictors of renal outcome.

Aspergillus fumigatus is a filamentous fungus that can infect the lungs of patients with immunosuppression and/or underlying lung diseases. The mortality associated with chronic and invasive aspergillosis infections remain very high, despite availability of antifungal treatments. In the last decade, there has been a worrisome emergence and spread of resistance to the first-line antifungals, the azoles. The mortality caused by resistant isolates is even higher, and patient management is complicated as the therapeutic options are reduced. Nevertheless, treatment failure is also common in patients infected with azole-susceptible isolates, which can be due to several non-mutually exclusive reasons, such as poor drug absorption. In addition, the phenomena of tolerance or persistence, where susceptible pathogens can survive the action of an antimicrobial for extended periods, have been associated with treatment failure in bacterial infections, and their occurrence in fungal infections already proposed. Here, we demonstrate that some isolates of A. fumigatus display persistence to voriconazole. A subpopulation of the persister isolates can survive for extended periods and even grow at low rates in the presence of supra-MIC of voriconazole and seemingly other azoles. Persistence cannot be eradicated with adjuvant drugs or antifungal combinations and seemed to reduce the efficacy of treatment for certain individuals in a Galleria mellonella model of infection. Furthermore, persistence implies a distinct transcriptional profile, demonstrating that it is an active response. We propose that azole persistence might be a relevant and underestimated factor that could influence the outcome of infection in human aspergillosis. Importance: The phenomena of antibacterial tolerance and persistence, where pathogenic microbes can survive for extended periods in the presence of cidal drug concentrations, have received significant attention in the last decade. Several mechanisms of action have been elucidated, and their relevance for treatment failure in bacterial infections demonstrated. In contrast, our knowledge of antifungal tolerance and, in particular, persistence is still very limited. In this study, we have characterized the response of the prominent fungal pathogen Aspergillus fumigatus to the first-line therapy antifungal voriconazole. We comprehensively show that some isolates display persistence to this fungicidal antifungal and propose various potential mechanisms of action. In addition, using an alternative model of infection, we provide initial evidence to suggest that persistence may cause treatment failure in some individuals. Therefore, we propose that azole persistence is an important factor to consider and further investigate in A. fumigatus. J.A. is funded by an Atracción de Talento Modalidad 1 (020-T1/BMD-200) contract of the Madrid Regional Government. J.S. has been funded by a BSAC Scholarship (bsac-2016-0049). C.V. was funded by FAPESP (2108/00715-3 and 2020/01131-5). G.H.G. hasbeen funded by FAPESP (2016/07870-9 and 2021/04977-5), CNPq (301058/2019-9 and404735/2018-5) and by the NIH/NIAID (grant R01AI153356). S.G. was cofunded by the NIHR Manchester Research Centre and the Fungal Infection Trust. Sí

Bees are important pollinators of agricultural crops, but their populations are at risk when pesticides are used. One of the largest risks bees face is poisoning of floral nectar and pollen by insecticides. Studies of bee detection of neonicotinoids have reported contradictory evidence about whether bees can taste these pesticides in sucrose solutions and hence avoid them. Here, we use an assay for the detection of food aversion combined with single-sensillum electrophysiology to test whether the mouthparts of the buff-tailed bumblebee (Bombus terrestris) detect the presence of pesticides in a solution that mimicked the nectar of oilseed rape (Brassica napus). Bees did not avoid consuming solutions containing concentrations of imidacloprid, thiamethoxam, clothianidin, or sulfoxaflor spanning six orders of magnitude, even when these solutions contained lethal doses. Only extremely high concentrations of the pesticides altered spiking in gustatory neurons through a slight reduction in firing rate or change in the rate of adaptation. These data provide strong evidence that bumblebees cannot detect or avoid field-relevant concentrations of pesticides using information from their mouthparts. As bees rarely contact floral nectar with other body parts, we predict that they are at high risk of unwittingly consuming pesticides in the nectar of pesticide-treated crops.

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting"approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.

Consider the simple matrix A on the left in Figure 1.1. Many of its entries are zero (and so are omitted). This is an example of a sparse matrix. The problem we are interested in is that of solving linear systems of equations Ax = b, where the square sparse matrix A and the vector b are given and the solution vector x is required. Such systems arise in a huge range of practical applications, including in areas as diverse as quantum chemistry, computer graphics, computational fluid dynamics, power networks, machine learning, and optimization. The list is endless and constantly growing, together with the sizes of the systems. For efficiency and to enable large systems to be solved, the sparsity of A must be exploited and operations with the zero entries avoided. To achieve this, sophisticated algorithms are required.

Consider a preconditioner M based on an incomplete LU (or Cholesky) factorization of a matrix A. M−1, which represents an approximation of A−1, is applied by performing forward and back substitution steps; this can present a computational bottleneck. An alternative strategy is to directly approximate A−1 by explicitly computing M−1. Preconditioners of this kind are called sparse approximate inverse preconditioners. They constitute an important class of algebraic preconditioners that are complementary to the approaches discussed in the previous chapter. They can be attractive because when used with an iterative solver, they can require fewer iterations than standard incomplete factorization preconditioners that contain a similar number of entries while offering significantly greater potential for parallel computations.

So far, our focus has been on the theoretical and algorithmic principles involved in sparse Gaussian elimination-based factorizations. To limit the storage and the work involved in the computation of the factors and in their use during the solve phase it is generally necessary to reorder (permute) the matrix before the factorization commences. The complexity of the most critical steps in the factorization is highly dependent on the amount of fill-in, as can be seen from the following observation.

Many sparse matrix algorithms exploit the close relationship between matrices and graphs. We make no assumption regarding the reader’s prior knowledge of graph theory. The purpose of this chapter is to summarize basic concepts from graph theory that will be exploited later and to establish the notation and terminology that will be used throughout.

This chapter considers the LU factorization of a general nonsymmetric nonsingular sparse matrix A. In practice, numerical pivoting for stability and/or ordering of A to limit fill-in in the factors is often needed and the computed factorization is then of a permuted matrix PAQ. Pivoting is discussed in Chapter 7 and ordering algorithms in Chapter 8.

Having considered the symbolic phase of a sparse Cholesky solver in the previous chapter, the focus of this chapter is the subsequent numerical factorization phase. If A is a symmetric positive definite (SPD) matrix, then it is factorizable (strongly regular) and (in exact arithmetic) its Cholesky factorization A = LLT exists. LDLT factorizations of general symmetric indefinite matrices are considered in Chapter 7.

This chapter focuses on the symbolic phase of a sparse Cholesky solver. The sparsity pattern $$\mathcal {S}\{A\}$$ S { A } of the symmetric positive definite (SPD) matrix A is used to determine the nonzero structure of the Cholesky factor L without computing the numerical values of the nonzeros.

When a matrix factorization is performed using finite precision arithmetic, the computed factors are not the exact factors. Despite this, the objective of sparse direct methods is normally to compute solutions that are accurate within the precision used. As discussed in Chapter 7, theoretical results can be used to assess both stability and accuracy.

This chapter introduces the basic concepts of Gaussian elimination and its formulation as a matrix factorization that can be expressed in a number of mathematically equivalent but algorithmically different ways.

Null-space methods have long been used to solve large sparse n × n symmetric saddle point systems of equations in which the (2, 2) block is zero. This paper focuses on the case where the (1, 1) block is ill conditioned or rank deficient and the k × k (2, 2) block is non zero and small (k ≪ n). Additionally, the (2, 1) block may be rank deficient. Such systems arise in a range of practical applications. A novel null-space approach is proposed that transforms the system matrix into a nicer symmetric saddle point matrix of order n that has a non zero (2, 2) block of order at most 2k and, importantly, the (1, 1) block is symmetric positive definite. Success of any null-space approach depends on constructing a suitable null-space basis. We propose methods for wide matrices having far fewer rows than columns with the aim of balancing stability of the transformed saddle point matrix with preserving sparsity in the (1, 1) block. Linear least squares problems that contain a small number of dense rows are an important motivation and are used to illustrate our ideas and to explore their potential for solving large-scale systems.

As the severe acute respiratory syndrome coronavirus 2 pandemic evolved and became a global health threat, the safety of immunosuppression in antineutrophil cytoplasmic antibody-associated vasculitis (AAV) became of utmost important for clinicians and patients. Although timely initiation of immunosuppressive therapy is critical to quell the acute inflammation and prevent AAV-associated mortality and morbidity, concerns for increased susceptibility to Coronavirus Disease 2019 (COVID-19), delayed viral clearance, and decreased humoral response to infection led to speculation about modification in induction therapy practices may be deployed by physicians caring for patients with AAV. This international retrospective cohort study investigated the influence of the COVID-19 pandemic on AAV induction therapy and patient outcomes in different parts of the world by studying differences in treatment regimens in the United States, United Kingdom, and Europe.

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop GN, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (usCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade usCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and ten controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, usCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic AKI. usCD163's specificity declined in patients with AAV who had nephrotic-range proteinuria and in those with primary podocytopathy, with 62% of patients with nephrotic syndrome displaying a "positive" usCD163. In patients with AAV and significant proteinuria, usCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions usCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates usCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

Undocumented Latina/os often describe their lives as ‘la lucha’, the struggle. To make ends meet ‘hay que batallar’, one must battle, work hard to ‘salir adelante’, get ahead. La lucha is interpret...

Athletes are vulnerable to sexual violence. Perpetrators of sexual violence may be a trusted coach, a member of the health care team, or a peer. The consequences of sexual violence are wide ranging, resulting in immediate and long-term physical and mental health outcomes that require recognition and comprehensive, multidisciplinary care. Sports medicine providers need to have specific knowledge and skill to care for athletes who experience sexual violence. Several sports organizations (e.g., International Olympic Committee, United States Olympic and Paralympic Committee, the National Collegiate Athletic Association, and the National Athletic Trainers' Association) have developed policies and procedures to prevent sexual violence and help sports medicine specialists provide care and services for athletes affected by sexual violence. Nevertheless, there remains a need for clinical guidelines, screening tools, and education, as well as clinical best practices to address sexual violence in sports medicine.

IMPORTANCE: Low back and neck pain are often self-limited, but health care spending remains high. OBJECTIVE: To evaluate the effects of 2 interventions that emphasize noninvasive care for spine pain. DESIGN, SETTING, AND PARTICIPANTS: Pragmatic, cluster, randomized clinical trial conducted at 33 centers in the US that enrolled 2971 participants with neck or back pain of 3 months’ duration or less (enrollment, June 2017 to March 2020; final follow-up, March 2021). INTERVENTIONS: Participants were randomized at the clinic-level to (1) usual care (n = 992); (2) a risk-stratified, multidisciplinary intervention (the identify, coordinate, and enhance [ICE] care model that combines physical therapy, health coach counseling, and consultation from a specialist in pain medicine or rehabilitation) (n = 829); or (3) individualized postural therapy (IPT), a postural therapy approach that combines physical therapy with building self-efficacy and self-management (n = 1150). MAIN OUTCOMES AND MEASURES: The primary outcomes were change in Oswestry Disability Index (ODI) score at 3 months (range, 0 [best] to 100 [worst]; minimal clinically important difference, 6) and spine-related health care spending at 1 year. A 2-sided significance threshold of .025 was used to define statistical significance. RESULTS: Among 2971 participants randomized (mean age, 51.7 years; 1792 women [60.3%]), 2733 (92%) finished the trial. Between baseline and 3-month follow-up, mean ODI scores changed from 31.2 to 15.4 for ICE, from 29.3 to 15.4 for IPT, and from 28.9 to 19.5 for usual care. At 3-month follow-up, absolute differences compared with usual care were −5.8 (95% CI, −7.7 to −3.9; P

PURPOSE OF REVIEW Liver disease (CFLD) as a complication of cystic fibrosis is recognized as a more severe disease phenotype in both children and adults. We review recent advances in understanding the disease mechanism and consider the implications of new strategies for the diagnosis and management of cystic fibrosis in those with evidence of clinically significant liver disease. RECENT FINDINGS Evidence suggests that the prevalence of CFLD has not declined with the introduction of newborn screening. Furthermore, children with CFLD, who have been diagnosed with cystic fibrosis following newborn screening continue to have a much higher mortality rate compared with those with no liver disease. There is further data suggesting noncirrhotic obliterative portal venopathy as the predominant pathological mechanism in the majority of children and young adults receiving a liver transplantation. Little progress has been made in developing an accurate noninvasive test for early diagnosis or monitoring disease progression in CFLD. The benefit of new modulator therapies is not well understood in those with established CFLD, whereas the risk of hepatotoxicity as a complication of treatment must be carefully monitored. SUMMARY Better understanding of the pathophysiology of CFLD would allow a standardized approach to diagnosis, with the potential to improve outcomes for those with CFLD.

Objective COVID-19 is a novel infectious disease with a broad spectrum of clinical severity. Patients with systemic vasculitis have an increased risk of serious infections and may be at risk of severe outcomes following COVID-19. We undertook this study to establish the risk factors for severe COVID-19 outcomes in these patients, including the impact of immunosuppressive therapies. Methods A multicenter cohort was developed through the participation of centers affiliated with national UK and Ireland vasculitis registries. Clinical characteristics and outcomes are described. Logistic regression was used to evaluate associations between potential risk factors and a severe COVID-19 outcome, defined as a requirement for advanced oxygen therapy, a requirement for invasive ventilation, or death. Results The cohort included 65 patients with systemic vasculitis who developed COVID-19 (median age 70 years, 49% women), of whom 25 patients (38%) experienced a severe outcome. Most patients (55 of 65 [85%]) had antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Almost all patients required hospitalization (59 of 65 [91%]), 7 patients (11%) were admitted to intensive care, and 18 patients (28%) died. Background glucocorticoid therapy was associated with severe outcomes (adjusted odds ratio [OR] 3.7 [95% confidence interval 1.1–14.9]; P = 0.047), as was comorbid respiratory disease (adjusted OR 7.5 [95% confidence interval 1.9–38.2]; P = 0.006). Vasculitis disease activity and nonglucocorticoid immunosuppressive therapy were not associated with severe outcomes. Conclusion In patients with systemic vasculitis, glucocorticoid use at presentation and comorbid respiratory disease were associated with severe outcomes in COVID-19. These data can inform clinical decision-making relating to the risk of severe COVID-19 in this vulnerable patient group.

Disasters affect the well-being of individuals, families and communities. Health and social care providers are essential in response and recovery efforts and are among the most vulnerable to negative physical and mental health impacts of a disaster. Few evidence-based interventions are available to address the psychological needs of providers. The aim of this study was to examine the psychological distress of health and social care providers before and after participating in the brief group intervention, Resilience and Coping for the Healthcare Community (RCHC) and its expanded version, RCHC+. We conducted a pragmatic non-randomised cluster trial with 762 health and social care providers in south Texas and Puerto Rico post-Hurricanes Harvey and Maria. Participants completed surveys assessing post-traumatic stress (PTSD), anxiety, burnout and secondary traumatic stress (STS) prior to intervention delivery and at two time points post-intervention. We calculated the frequency of symptom cut-off scores at baseline, then estimated multilevel ordinal models to examine changes in symptoms across time. Prior to participation in the RCHC (approximately 12 months after the hurricanes), providers reported high levels of PTSD, anxiety and STS symptoms. After participation, providers in both intervention conditions reported a significant reduction in PTSD symptoms from baseline that was sustained over both time points. The likelihood of a reduction in symptoms of anxiety and STS from baseline was sustained at both time points for participants in the RCHC+ condition. These findings indicate that both the RCHC and RCHC+ interventions may reduce psychological distress for health and social care providers and could be an important part of advance planning to support provider's mental health during and after a disaster. Further examination of the RCHC in other disaster contexts could provide additional insight into the responsiveness of the intervention to reducing psychological distress symptoms.