Rapid Growth of Large Forest Fires Drives the Exponential Response of Annual Forest-Fire Area to Aridity in the Western United States.

Annual forest area burned (AFAB) in the western United States (US) has increased as a positive exponential function of rising aridity in recent decades. This non-linear response has important implications for AFAB in a changing climate, yet the cause of the exponential AFAB-aridity relationship has not been given rigorous attention. We investigated the exponential AFAB-aridity relationship in western US forests using a new 1984-2019 database of fire events and 2001-2020 satellite-based records of daily fire growth. While forest-fire frequency and duration grow linearly with aridity, the exponential AFAB-aridity relationship results from the exponential growth rates of individual fires. Larger fires generally have more potential for growth due to more extensive firelines. Thus, forces that promote fire growth, such as aridification, have more potent effects on larger fires. As aridity increases linearly, the potential for growth of large fires accelerates, leading to exponential increases in AFAB.

Historical droughts recorded in extended Juniperus procera ring-width chronologies from the Ethiopian Highlands.

In the Horn of Africa, little is known about temporal changes in hydroclimate owing to the influence of multiple weather systems, the complex terrain, and the sparse instrumental records. Absolutely dated tree-ring records offer the potential to extend our understanding of climate into the pre-instrumental era, but tree-ring studies in this region, and indeed all of tropical Africa, have been rare largely due to lack of an annual climate cycle that reliably produces annual tree-rings. In this study, 40 cores were obtained from 31 Juniperus procera trees growing in the grounds of Ethiopian Orthodox Tewahedo churches in the Gonder region of Ethiopia. The samples were cross-dated using a re-iterative process involving identifying anatomical features from high-resolution images. The tentative ring-width chronologies were revised after the determination of bomb-peak accelerator mass spectrometry radiocarbon dates. Individual series were significantly correlated to the respective master chronologies (r > 0.55; P < 0.05), and expressed population signal values ranged from 0.55 to 0.92. Historical drought years were successfully traced in the chronologies by pointer year analysis. This study confirms that Juniperus procera growing in areas of unimodal precipitation exhibits annual tree-rings and offers the potential as an indirect measure of past climate.

Clinical and laboratory features of seventy-eight UK patients with Good's syndrome (thymoma and hypogammaglobulinaemia).

Good's syndrome (thymoma and hypogammaglobulinaemia) is a rare secondary immunodeficiency disease, previously reported in the published literature as mainly individual cases or small case series. We use the national UK-Primary Immune Deficiency (UKPID) registry to identify a large cohort of patients in the UK with this PID to review its clinical course, natural history and prognosis. Clinical information, laboratory data, treatment and outcome were collated and analysed. Seventy-eight patients with a median age of 64 years, 59% of whom were female, were reviewed. Median age of presentation was 54 years. Absolute B cell numbers and serum immunoglobulins were very low in all patients and all received immunoglobulin replacement therapy. All patients had undergone thymectomy and nine (12%) had thymic carcinoma (four locally invasive and five had disseminated disease) requiring adjuvant radiotherapy and/or chemotherapy. CD4 T cells were significantly lower in these patients with malignant thymoma. Seventy-four (95%) presented with infections, 35 (45%) had bronchiectasis, seven (9%) chronic sinusitis, but only eight (10%) had serious invasive fungal or viral infections. Patients with AB-type thymomas were more likely to have bronchiectasis. Twenty (26%) suffered from autoimmune diseases (pure red cell aplasia, hypothyroidism, arthritis, myasthenia gravis, systemic lupus erythematosus, Sjögren's syndrome). There was no association between thymoma type and autoimmunity. Seven (9%) patients had died. Good's syndrome is associated with significant morbidity relating to infectious and autoimmune complications. Prospective studies are required to understand why some patients with thymoma develop persistent hypogammaglobulinaemia.

Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics.

Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next-generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty-seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.

Multi-centre retrospective analysis of anaphylaxis during general anaesthesia in the United Kingdom: aetiology and diagnostic performance of acute serum tryptase.

This is the first multi-centre retrospective survey from the United Kingdom to evaluate the aetiology and diagnostic performance of tryptase in anaphylaxis during general anaesthesia (GA). Data were collected retrospectively (2005-12) from 161 patients [mean ± standard deviation (s.d.), 50 ± 15 years] referred to four regional UK centres. Receiver operating characteristic curves (ROC) were constructed to assess the utility of tryptase measurements in the diagnosis of immunoglobulin (Ig)E-mediated anaphylaxis and the performance of percentage change from baseline [percentage change (PC)] and absolute tryptase (AT) quantitation. An IgE-mediated cause was identified in 103 patients (64%); neuromuscular blocking agents (NMBA) constituted the leading cause (38%) followed by antibiotics (8%), patent blue dye (6%), chlorhexidine (5%) and other agents (7%). In contrast to previous reports, latex-induced anaphylaxis was rare (0·6%). A non-IgE-mediated cause was attributed in 10 patients (6%) and no cause could be established in 48 cases (30%). Three serial tryptase measurements were available in 34% of patients and a ROC analysis of area under the curve (AUC) showed comparable performance for PC and AT. A ≥ 80% PPV for identifying an IgE-mediated anaphylaxis was achieved with a PC of >141% or an AT of >15·7 mg/l. NMBAs were the leading cause of anaphylaxis, followed by antibiotics, with latex allergy being uncommon. Chlorhexidine and patent blue dye are emerging important health-care-associated allergens that may lead to anaphylaxis. An elevated acute serum tryptase (PC >141%, AT >15·7 mg/l) is highly predictive of IgE-mediated anaphylaxis, and both methods of interpretation are comparable.

A quantitative risk assessment for the safety of carcase storage systems for scrapie infected farms.

AIMS: To determine the risk associated with the use of carcase storage vessels on a scrapie infected farm. METHODS AND RESULTS: A stochastic quantitative risk assessment was developed to determine the rate of accumulation and fate of scrapie in a novel low-input storage system. For an example farm infected with classical scrapie, a mean of 10(3·6) Ovine Oral ID50 s was estimated to accumulate annually. Research indicates that the degradation of any prions present may range from insignificant to a magnitude of one or two logs over several months of storage. CONCLUSIONS: For infected farms, the likely partitioning of remaining prion into the sludge phase would necessitate the safe operation and removal of resulting materials from these systems. If complete mixing could be assumed, on average, the concentrations of infectivity are estimated to be slightly lower than that measured in placenta from infected sheep at lambing. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first quantitative assessment of the scrapie risk associated with fallen stock on farm and provides guidance to policy makers on the safety of one type of storage system and the relative risk when compared to other materials present on an infected farm.

Combining risk assessment and epidemiological risk factors to elucidate the sources of human E. coli O157 infection.

E. coli O157 can be transmitted to humans by three primary (foodborne, environmental, waterborne) and one secondary (person-to-person transmission) pathways. A regression model and quantitative microbiological risk assessments (QMRAs) were applied to determine the relative importance of the primary transmission pathways in NE Scotland. Both approaches indicated that waterborne infection was the least important but it was unclear whether food or the environment was the main source of infection. The QMRAs over-predicted the number of cases by a factor of 30 and this could be because all E. coli O157 strains may not be equally infective and/or the level of infectivity in the dose-response model was too high. The efficacy of potential risk mitigation strategies to reduce human exposure to E. coli O157 using QMRAs was simulated. Risk mitigation strategies focusing on food and environment are likely to have the biggest impact on infection figures.

Escherichia coli O157: comparing awareness of rural residents and visitors in livestock farming areas.

This research compared public opinions about Escherichia coli O157 (an increasing environmental hazard associated with livestock) in two farming areas with contrasting incidence of E. coli O157 disease. A questionnaire was administered in rural Grampian (10·8 cases/100,000 population per year) and North Wales (2·5 cases/100,000 population per year). Awareness was highest among farmers in Grampian (91%) and lowest among visitors to both areas (28%). Respondents were more likely to indicate vomiting (76%) than bloody diarrhoea (48%) as a common symptom. Undercooked meat and contact with farm animal faeces were identified by 60% of all respondents as risk factors who described 'basic hygiene' for risk reduction indoors. Visitors view E. coli O157 as a food hazard, not an environmental hazard that produces vomiting not dysentery. Efforts to reduce human infections in livestock farming areas could be improved with proximate reminders for visitors of the environmental pathway of E. coli O157 infection.

Grazing intensity is a poor indicator of waterborne Escherichia coli O157 activity.

Contamination of watercourses with fecal matter represents a significant risk to public health due to the associated risk from human pathogens (e.g. Escherichia coli O157, norovirus). In addition, water contamination may also perpetuate the re-infection cycle of human pathogens within domesticated and wild animal populations. While diffuse pollution from agricultural fields has been identified as a major source of these pathogens, the relationship between livestock grazing intensity and subsequent pathogen persistence in water is not well established. Our aim was to critically evaluate the importance of land use management on the activity of E. coli O157 in freshwaters collected from a livestock dominated catchment in the UK. We inoculated replicate batches of both filter-sterilised and non-sterile freshwaters with a chromosomally lux-marked E. coli O157 and monitored pathogen survival and activity over a 5 d period. Our results indicate that the greatest risk for pathogens entering freshwater is probably associated with high intensity livestock areas, although their subsequent survival is greatest in waters from low intensity livestock areas. We ascribe this enhanced persistence in the latter to reduced competition and predation within these aquatic environments. These results have serious implications for the reliability of pathogen risk exposure maps which are based on grazing intensity alone.

Spatial behaviour of sheep during the neonatal period: Preliminary study on the influence of shelter.

Effective shelter has been demonstrated to reduce neonatal lamb mortality rates during periods of inclement weather. Periods of high wind speed and rainfall have been shown to influence shelter usage; however, it is not yet known how ewe factors such as breed, age and body condition score influence shelter-seeking behaviour. This study, conducted on a working upland farm in the UK, examined impact of artificial shelter on the biological and climatic factors that influence peri-parturient ewe behaviour. Pregnant ewes (n = 147) were randomly allocated between two adjacent fields which were selected for their similarity in size, topography, pasture management, orientation to the prevailing wind and available natural shelter. In one field, three additional artificial shelters were installed to increase the available shelter for ewes, this field was designated the Test field; no additional artificial shelter was provided in the second field which was used as the Control field. Individual ewes were observed every 2 h between 0800 and 1600 for 14 continuous days to monitor their location relative to shelter. Ewe breed (Aberfield and Highlander), age (2-8 years) and body condition score were considered as explanatory variables to explain flock and individual variance in shelter-seeking behaviour and the prevalence of issues which required the intervention of the shepherd, termed 'shepherding problems'. Any ewe observed with dystocia, a dead or poor vigour lamb or who exhibited mismothering behaviour was recorded as a shepherding problem. The prevalence of these shepherding problems which necessitate human intervention represents arguably the most critical limiting factor for the successful management of commercial sheep flocks in outdoor lambing systems. Overall, ewes in the Test field with access to additional artificial shelter experienced fewer shepherding problems than those in the Control field (P < 0.05). A significant breed effect was also observed, with Highlander ewes more likely to seek shelter than Aberfield ewes (P < 0.001), and experiencing significantly fewer shepherding interventions (P < 0.05). These findings demonstrate the substantial and significant benefits to animal welfare and productivity that can be achieved through the provision of shelter in commercial, upland, outdoor lambing systems in the UK.

Microbiological quality of chicken wings damaged on the farm or in the processing plant.

Selling of damaged chicken wings (those with bone protrusion) for human consumption is prohibited in the European Union on the grounds of possible risks to human health arising from microbial contamination. Standard food industry tests were used to assess different categories of chicken wings (undamaged, farm damaged and factory damaged; n = 264) for, coliforms, Enterobacteriaceae, total viable counts, Pseudomonas spp., Staphylococcus aureus and Salmonella spp. No significant differences in bacterial numbers existed among wings belonging to the three categories. Only low numbers of bacteria were found throughout, and 97% of all results would pass the standards of a leading UK retailer. These results were strengthened by a longitudinal survey of wing breakage, which showed almost all wing puncturing occurred during the de-feathering process, limiting the likelihood of microbial contamination. Combined, these results indicate there is no increased health risk from consumption of damaged, compared to undamaged, chicken wings. The existing imposed regulations may therefore be an unnecessary burden on the poultry industry.

Leaching of bioluminescent Escherichia coli O157:H7 from sheep and cattle faeces during simulated rainstorm events.

AIMS: Development of a novel inoculation technique to improve the current methods of determining the leaching of Escherichia coli O157:H7 from faeces. METHODS AND RESULTS: Ruminant faeces were inoculated with a high [c. 10(7) colony forming units (CFU) g(-1)] or low (c. 10(4) CFU g(-1)) load of a lux-marked strain of E. coli O157:H7 via injection, and subjected to four simulated heavy rainfall events. The population density and metabolic activity of E. coli O157:H7 recovered within the leachate was determined following each simulated rain event and compared with the indigenous E. coli population. The concentration of E. coli O157:H7 in the leachates followed a similar trend to that of nonpathogenic E. coli. Significantly greater densities of generic and pathogenic E. coli were recovered in the leachates generated from sheep faeces compared with cattle faeces. Pathogen metabolic activity was also significantly greater in sheep faeces. CONCLUSIONS: Our findings show that E. coli O157:H7 may readily leach from ruminant faeces during rain events. The bacterium leaches more freely from sheep faeces than from cattle faeces and displays greater metabolic activity within sheep leachate. SIGNIFICANCE AND IMPACT OF THE STUDY: A novel inoculation technique was developed that allowed the determination of both population density and cellular activity of E. coli O157:H7 in leachate derived from faeces.

Survival of Escherichia coli O157:H7 in waters from lakes, rivers, puddles and animal-drinking troughs.

Survival of Escherichia coli O157:H7 in surface waters may increase the potential for dissipation of the organism to facilitate cycles of livestock re-infection and lead to human infection. Although previous studies have monitored survival of the organism in a range of surface waters, there is limited information on the influence of physico-chemical characteristics on persistence. Microcosms of four different surface water types (n=31) from the UK were inoculated with E. coli O157:H7 and incubated at 10 degrees C. The water types studied were: lake, puddle, river, and animal-drinking trough waters. Numbers of E. coli O157:H7 declined over time in all waters, although cells were still detected in 45% of non-sterile samples after 2 months. Persistence of E. coli O157:H7 was enhanced by water aeration and by prior sterilisation; however there was no correlation between water chemistry and mean E. coli O157:H7 die-off times or rates in any water type. Survival of the pathogen was better in lake and puddle waters than in river or drinking trough waters. Further studies are needed to establish the key water quality factors that regulate pathogen survival.

Association of Surgeons in Training conference: Bournemouth 2017.

The Association of Surgeons in Training (ASiT) is a professional body and registered charity working to promote excellence in surgical training for the benefit of junior doctors and patients alike. The Association provides support at both regional and national levels throughout the United Kingdom and Republic of Ireland. Originally founded in 1976, ASiT is independent of the National Health Service (NHS), Surgical Royal Colleges, and specialty associations. The 2017 Annual Conference in Bournemouth brought together over 700 delegates for a diverse educational weekend with numerous expert guest speakers. With a theme of '#AdvancesIn,' we looked to celebrate cutting edge progress in training, clinical management, medical technology, leadership and entrepreneurialism. These updates were complimented by debates on current training in surgery and an array of focussed parallel sessions. For the first time, delegates were also able to interact with the conference digitally, with the debut of our conference smartphone App. The weekend started with 9 pre-conference courses covering a diverse range of topics including core laparoscopic, vascular, orthopaedics, neurosurgical skills, leadership and global surgery. Over 1000 abstract submissions were received and those successful competed for over 30 awards, representing nearly £4000 in trainee prizes and bursaries. As the only national surgical trainee meeting for all specialties, ASiT continues to grow and we look forward to an even larger and more successful international conference next year in Edinburgh 6-8th April 2018 with the theme of #nurturingexcellence.

IL-10 production by CLL cells is enhanced in the anergic IGHV mutated subset and associates with reduced DNA methylation of the IL10 locus.

Chronic lymphocytic leukemias (CLLs) with unmutated (U-CLL) or mutated (M-CLL) IGHV have variable features of immunosuppression, possibly influenced by those CLL cells activated to produce interleukin 10 (IL-10). The two subsets differ in their levels of anergy, defined by low surface immunoglobulin M levels/signaling capacity, and in their DNA methylation profile, particularly variable in M-CLL. We have now found that levels of IL-10 produced by activated CLL cells were highly variable. Levels were higher in M-CLL than in U-CLL and correlated with anergy. DNA methylation analysis of IL10 locus revealed two previously uncharacterized 'variably methylated regions' (CLL-VMRs1/2) in the gene body, but similarly low methylation in the promoter of both U-CLL and M-CLL. CLL-VMR1/2 methylation was lower in M-CLL than in U-CLL and inversely correlated with IL-10 induction. A functional signal transducer and activator of transcription 3 (STAT3) binding site in CLL-VMR2 was confirmed by proximity ligation and luciferase assays, whereas inhibition of SYK-mediated STAT3 activation resulted in suppression of IL10. The data suggest epigenetic control of IL-10 production. Higher tumor load may compensate the reduced IL-10 production in U-CLL, accounting for clinical immunosuppression in both subsets. The observation that SYK inhibition also suppresses IL-10 provides a potential new rationale for therapeutic targeting and immunological rescue by SYK inhibitors in CLL.

FOREST ECOLOGY. Pervasive drought legacies in forest ecosystems and their implications for carbon cycle models.

The impacts of climate extremes on terrestrial ecosystems are poorly understood but important for predicting carbon cycle feedbacks to climate change. Coupled climate-carbon cycle models typically assume that vegetation recovery from extreme drought is immediate and complete, which conflicts with the understanding of basic plant physiology. We examined the recovery of stem growth in trees after severe drought at 1338 forest sites across the globe, comprising 49,339 site-years, and compared the results with simulated recovery in climate-vegetation models. We found pervasive and substantial "legacy effects" of reduced growth and incomplete recovery for 1 to 4 years after severe drought. Legacy effects were most prevalent in dry ecosystems, among Pinaceae, and among species with low hydraulic safety margins. In contrast, limited or no legacy effects after drought were simulated by current climate-vegetation models. Our results highlight hysteresis in ecosystem-level carbon cycling and delayed recovery from climate extremes.

The putative essential nutrient pyrroloquinoline quinone is neuroprotective in a rodent model of hypoxic/ischemic brain injury.

Pyrroloquinoline quinone is a ubiquitous redox cofactor and putative essential nutrient in mammals. Pyrroloquinoline quinone has recently been demonstrated to depress N-methyl-D-asparate induced electrical responses and is neuroprotective in vitro. In addition, pyrroloquinoline quinone has been demonstrated to act as a free radical scavenger in mammalian tissues. In this study, we demonstrate a neuroprotective effect of pyrroloquinoline quinone in an in vivo cerebral hypoxia/ischemia model in the rodent. Significant reduction in infarct size resulted from pyrroloquinoline quinone pretreatment and also when pyrroloquinoline quinone was administered following induction of hypoxia/ischemia. The neuroprotective effect was not dependent on change in core or cranial temperatures, as there was no difference between temperature measurements in pyrroloquinoline quinone-treated and vehicle-treated controls. No changes in electroencephalographic activity were observed at neuroprotective doses. These findings suggest that pyrroloquinoline quinone may represent a novel class of quinoid reagents of potential use in the treatment of neurological disorders that involve excitotoxicity. This study demonstrates a protective effect of the novel essential nutrient pyrroloquinoline quinone on brain injury in a rodent model of cerebral hypoxia/ischemia. Pyrroloquinoline quinone was neuroprotective when administered before and even after the insult, and did not appear to have significant neurobehavioral side effects. Pyrroloquinoline quinone represents a new class of agents with potential use in the therapy of stroke.

How many physicians will be needed to provide medical care for older persons? Physician manpower needs for the twenty-first century.

To estimate the number of full-time-equivalent (FTE) physicians and geriatricians needed to provide medical care in the years 2000 to 2030, we developed utilization-based models of need for non-surgical physicians and need for geriatricians. Based on projected utilization, the number of FTE physicians required to care for the elderly will increase two- or threefold over the next 40 years. Alternate economic scenarios have very little effect on estimates of FTE physicians needed but exert large effects on the projected number of FTE geriatricians needed. We conclude that during the years 2000 to 2030, population growth will be the major factor determining the number of physicians needed to provide medicare care; economic forces will have a greater influence on the number of geriatricians needed.