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Ice core data record significant and abrupt past climate changes that are associated with large and rapid changes in atmospheric greenhouse gases, such as methane. Due to the gradual close‐off of gas bubbles and the relatively fast diffusion of gases within the firn column, even a discrete or quick step increase in air composition may be smoothed or integrated in the data; current laboratory analyses of gases consider the mean gas content value across all bubbles in a sample, rather than the content of individual bubbles. The convolution of the distribution of trapping ages with the history of atmospheric composition thus smears the measured gas record in each sample. We developed a nondestructive method to determine pressure distribution in all bubbles in a sample and estimate the shape of the trapping function derived from that bubble pressure distribution and site characteristics. Our method works not only for present conditions but also through varying paleo‐atmospheric conditions, while providing accurate measurements of morphological bubble properties. The method is based on using temperature‐driven air bubble migration as a proxy for the pressure of individual bubbles, which we combine with a model for bubbly ice densification to obtain the gas trapping functions and constrain the age distribution of air bubbles for past conditions, which are preserved at different depths. The trapping functions will help us to obtain a more accurate gas signal in the future that is less attenuated through the age distribution of the gas during the close‐off process. Key Points: The gas pressure distribution in bubbly ice can be inferred by measuring velocities of bubbles migrating under a temperature gradientThe bubble close‐off history can be reconstructed from the pressure distributionGas‐trapping functions can be determined for different depths (climatic periods) [ABSTRACT FROM AUTHOR]

A microwave torch in nitrogen has been designed for the evaporation of aluminium (Al) wires potentially to be used for the synthesis of aluminium nitride (AlN). The torch, created on the tip of a metallic nozzle, is compatible with vacuum conditions and can be operated in continuous mode up to atmospheric pressure. Al wires to be evaporated are fed through the axis of the nozzle. Time‐resolved photography is applied to analyse the time evolution and stability of the interaction of the Al wire with the discharge. Optical emission spectroscopy is used (a) for the determination of the gas temperature of the active discharge, which is found to be in the range 1500–3500 K depending on the experimental conditions, and (b) for the estimation of the densities of Al and N atoms in the afterglow region, which are in the range 1011–1012 and of 1013–1014 cm−3, respectively. It is found that the part of the Al wire that is directly exposed to the nitrogen torch absorbs a considerable amount of the microwave energy, supporting its evaporation. In addition, the dissociation of molecular nitrogen has to be considered as an important process of power dissipation. Further technical development of the torch is necessary for the envisaged synthesis of AlN. [ABSTRACT FROM AUTHOR]

Background This paper examines the development and psychometric characteristics of three instruments about end of life, designed for use with adults with intellectual disability ( ID). Respectively, the instruments assess understanding of the concept of death, end-of-life planning, and fear of death. Methods Part 1: instruments were developed or adapted, and pilot tested with 11 adults with ID and 2 disability staff. Part 2: 39 adults with ID and 40 disability staff were assessed on all three instruments. Results We evaluated comprehensibility, internal consistency, inter-rater reliability, subscale: total score correlations, missing data, and withdrawal. Psychometric findings were mostly good. Overall, 23% of participants with ID withdrew at some point. This outcome may have been as much due to assessment fatigue as to sensitive content. There were no adverse events. Conclusions People with ID can reliably complete assessments about end-of-life. Generally, each instrument was found to be comprehensible, reliable and valid. [ABSTRACT FROM AUTHOR]

Background Allergen immunotherapy uses pharmaceutical preparations derived from naturally occurring source materials, which contain water-soluble allergenic components responsible for allergic reactions. The success of in vivo and in vitro diagnoses in allergen sensitization and allergen immunotherapy largely depends on the quality, composition and uniformity of allergenic materials used to produce the active ingredients, and the formulation employed to prepare finished products. Objectives We aimed to examine the factors influencing batch-to-batch consistency of Jack Jumper ( Myrmecia pilosula) ant venom ( JJAV) in the form of active pharmaceutical ingredient ( AI) and informed whether factors such as temperature, artificial light and container materials influence the quality of JJAV AIs. We also aimed to establish handling and storage requirements of JJAV AIs to ensure preservation of allergenic activities during usage in the diagnosis of allergen sensitization and in allergen immunotherapy. Methods The quality and consistency of JJAV AIs were analysed using a combination of bicinchoninic acid assay for total protein quantification, HPLC- UV for JJAV allergen peptides quantification, ELISA inhibition for total allergenic potency, SDS- PAGE, AU- PAGE and immunoblot for qualitative assessment of JJAV components, and Limulus Amebocyte Lysate assay for the quantification of endotoxin concentration. API- ZYM and Zymogram assays were used to probe the presence of enzymatic activities in JJAV. Results Pharmaceutical-grade JJAV for allergen immunotherapy has good batch-to-batch consistency. Temporary storage at 4°C and light exposure do not affect the quality of JJAV. Exposure to temperature above 40°C degrades high MW allergens in JJAV. Vials containing JJAV must be stored frozen and in upright position during long-term storage. Conclusions and Clinical Relevance We have identified factors, which can influence the quality and consistency of JJAV AIs, and provided a framework for appropriate handling, transporting and storage of JJAV to be used for the diagnosis of allergen sensitization and in AIT. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is associated with fatigue and depression. Cognitive impairments are also reported in a smaller number of HCV-positive patients. Recent studies linked HCV to low-grade inflammation in brain. Here, we test the hypothesis that chronic HCV is associated with 3T-neuroimaging-derived grey matter volume (GMV) and functional connectivity alterations in a sample of chronic HCV (1b), without severe liver disease. Regional GMV and resting-state fMRI-derived eigenvector centrality (EC) were compared between 19 HCV-positive patients and 23 healthy controls (all females, 50-69 and 52-64 years, respectively), controlling for white matter hyperintensities and age. Standard tests were used to assess fatigue, depression and cognitive performance. Also, liver fibrosis stage and viral load were quantified among patients. In comparison with controls, HCV-positive patients had higher scores in fatigue and depression, and worse alertness scores. The groups performed similarly in other cognitive domains. We report higher EC in a cluster in the right anterior superior parietal lobule in patients, while no differences are found in GMV. Post hoc functional connectivity analysis showed increased connectivity of this cluster with primary and secondary somatosensory cortex, and temporal and occipital lobes in patients. Higher mean EC in the superior parietal cluster, adjusted for mean framewise displacement, was associated with better memory and attention performance, but not with fatigue, depression, viral load or level of liver fibrosis, among patients. These results suggest a compensatory mechanism in chronic hepatitis C and explain equivocal results in the literature about cognitive deficits in infected persons. Further studies should define the relation of these connectivity changes to the brain's inflammatory activity. [ABSTRACT FROM AUTHOR]

Background Current peanut oral immunotherapy is hampered by frequent adverse events. It has been shown that boiling can reduce peanut allergenicity. Hypoallergenic peanut products have the potential to reduce treatment-related reactions during desensitization. Objective To show that extended boiling (for up to 12 h) can progressively reduce peanut allergenicity while retaining T cell reactivity. Methods Raw peanuts were boiled for half, 1, 2, 4 and 12 h in deionized water. After dehydration, boiled and raw peanuts were ground, defatted and soluble proteins extracted in PBS and cooking water (leachate) retained. SDS- PAGE, Western blot, inhibition ELISA, mass spectrometry and skin prick test were used to characterize changes to peanut allergens and human IgE reactivity. T cell responses to raw and boiled peanut extracts were determined by proliferation of CD4+/ CD25+/ CD134+ T cells in peanut-allergic and non-allergic individuals. Results Extended boiling progressively reduced peanut allergenicity through a combination of leaching of allergens into cooking water, fragmentation of allergens and denaturation of conformational epitopes. Two-hour boiling led to an eightfold reduction in IgE binding capacity of boiled peanuts as determined by inhibition ELISA, while 12-h boiling led to a 19-fold reduction. Mass spectrometry revealed an increasing number of unique allergen peptides with longer boiling times. Raw, 2- and 12-h boiled peanut extracts were equivalent in their ability to stimulate T cell activation and proliferation. Conclusion and Clinical Relevance Progressive reduction in peanut allergenicity with extended boiling does not affect T cell reactivity. Boiled peanuts may be a candidate for oral immunotherapy. [ABSTRACT FROM AUTHOR]

In Europe, healthcare systems differ between countries and different factors may influence Chronic hepatitis B ( CHB) treatment choices in different counties. This analysis from a prospective, longitudinal, non-interventional study in five EU countries aimed to explore determinants associated with treatment initiation or switch in patients with CHB. A total of 1267 adult patients with compensated CHB in Germany, France, Poland, Romania and Turkey were prospectively followed for up to 2 years (March 2008-December 2010). Determinants of treatment initiation or switch were analysed using multivariate Cox proportional hazards regression. Median time since CHB diagnosis was 2.6 (0-37.7) years. Among 646 treatment-naïve patients, the probability of treatment initiation during follow-up was higher: in Germany ( P = 0.0006), Poland ( P < 0.0001) and Romania ( P = 0.0004) compared with Turkey; in patients with alanine transaminase (ALT) 1-2 × upper limit of normal (ULN) ( P = 0.0580) or >2 × ULN ( P = 0.0523) compared with ALT ≤1 × ULN; and in patients with hepatitis B virus (HBV) DNA ≥2000 IU/mL ( P < 0.0001) compared with HBV DNA <2000 IU/mL or undetectable. Among 567 treated patients, 87 switched treatment during follow-up. The probability of treatment switch was higher: in France ( P = 0.0029), Germany ( P = 0.0078) and Poland ( P = 0.0329) compared with Turkey; and in patients with HBV DNA <2000 ( P < 0.0001) or ≥2000 IU/mL ( P < 0.0001), compared with undetectable. Viral load and ALT level were identified as the major drivers of treatment initiation. HBV DNA level was also a significant determinant of treatment switch. Results were statistically different across EU countries. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to explore what community living staff talked about and did with people with intellectual disability ( ID) to assist them to understand dying and death. Method Guided by grounded theory methodology, focus groups and one-to-one interviews were conducted with 22 staff who had talked about any topic relating to dying and death with their clients. Results There was little evidence that staff talked with, or did things with clients to assist understanding of the end of life, both prior to and after a death. Prior to death staff assisted clients in a limited way to understand about determining wishes in preparation for death, and what dying looks like by observance of its passage. Following a death staff offered limited assistance to clients to understand the immutability of death, and how the dead can be honoured with ritual, and remembered. Conclusions The findings have implications for why people with ID have only partial understanding of the end of life, the staff skills required to support clients' understanding, and when conversations about the end of life should occur. [ABSTRACT FROM AUTHOR]

Background The aim of this study was to explore the way in which community living staff engaged with people with intellectual disability (ID) about dying and death. Method Guided by grounded theory methodology, focus groups and individual interviews were conducted with staff who had either no experience with client death, experience of a client sudden death, or a client death experience which was pre-dated by a period of end-of-life care. Results While in principle, staff unanimously supported the belief that people with ID should know about dying, there was limited in-practice engagement with clients about the topic. Engagement varied according to staff experience, client capacity to understand and the nature of the 'opportunity' to engage. Four 'opportunities' were identified: 'when family die', 'incidental opportunities', 'when clients live with someone who is dying' and 'when a client is dying'. Despite limited engagement by staff, people with ID are regularly exposed to dying and death. Conclusions People with ID have a fundamental right to know about dying and death. Sophisticated staff skills are required to ensure that people with ID can meaningfully engage with end-of-life issues as opportunities arise. [ABSTRACT FROM AUTHOR]

From 2010 to 2012, nine systematic reviews reported highly variable conclusions regarding the association between carriage of a cytochrome P450 2C19 loss-of-function allele and the risk of adverse cardiovascular (CV) events in individuals using clopidogrel. Possible contributors to the variable findings include differences in patient populations, CV end points, and statistical models utilized by the systematic reviews, as well as unexplained heterogeneity, inconsistent/incomplete reporting, and risk of publication bias with respect to the primary studies. [ABSTRACT FROM AUTHOR]

Background: Urticaria, angioedema and anaphylaxis are common adverse reactions to non-steroidal anti-inflammatory drugs (NSAIDs). Aim: To investigate the clinical characteristics of NSAID-induced acute hypersensitivity reactions with structured oral drug challenges. Methods: Patients with NSAID-induced urticaria, angioedema or anaphylaxis were challenged with either the homologous NSAID to confirm diagnosis or a heterologous NSAID to investigate cross-reactivity. Data were analysed retrospectively and supplemented by a telephone questionnaire. Results: Sixty-eight patients (mean age 48.3, 53 females) reported a total of 75 instances of NSAID-induced reactions of which 64% were purely cutaneous and 36% were systemic anaphylaxis. Ibuprofen was the most frequent cause of reactions (35%), however, diclofenac was the most frequent cause of anaphylaxis (48%). Seventeen out of 40 (43%) homologous NSAID challenges were positive; presentation with anaphylaxis or reaction to diclofenac predicted a positive challenge. Only 7 of 28 (25%) of heterologous NSAID challenges were positive. Structured challenges enabled us to identify 23 (34%) patients with selective reactivity to a single NSAID, 19 (28%) patients with cross-reactivity to multiple NSAIDs and 23 (34%) patients in whom NSAID hypersensitivity was not reproduced. Selective reactors presented most often with anaphylaxis and some had a background of beta-lactam antibiotic allergy. Cross-reactive patients often had a background of chronic urticaria and presented with milder reactions. Conclusion: In the absence of a reliable in vitro test, structured drug challenges allow identification of selective and cross-reactive NSAID hypersensitivity syndromes. NSAID-induced anaphylaxis is often associated with selective hypersensitivity and patients may not need to avoid other NSAIDs. [ABSTRACT FROM AUTHOR]

Summary 1. There should be protocol-driven, fast-track admission of patients with hip fractures through the emergency department. 2. Patients with hip fractures require multidisciplinary care, led by orthogeriatricians. 3. Surgery is the best analgesic for hip fractures. 4. Surgical repair of hip fractures should occur within 48 hours of hospital admission. 5. Surgery and anaesthesia must be undertaken by appropriately experienced surgeons and anaesthetists. 6. There must be high-quality communication between clinicians and allied health professionals. 7. Early mobilisation is a key part of the management of patients with hip fractures. 8. Pre-operative management should include consideration of planning for discharge from hospital. 9. Measures should be taken to prevent secondary falls. 10. Continuous audit and targeted research is required in order to inform and improve the management of patients with hip fracture. [ABSTRACT FROM AUTHOR]

Little is known comparing and contrasting quality of life (QoL) in patients with hepatitis C, compared to patients with other liver diseases. We performed two independent prospective cross-sectional studies including 511 and 284 patients with different forms of liver diseases. SF-36 was used in both studies. Fatigue Impact Score, WHO-BREF and Hospital Anxiety and Depression Scale (HADS) were used in either study only. In both studies, HCV-positive patients scored worse in the mental aspects of health-related QoL compared to other liver diseases, except for HBV in one study. Surprisingly, in both studies, quality of life was also significantly impaired in patients with viral clearance after interferon therapy but not after spontaneous clearance. Furthermore, patients with primary biliary cirrhosis showed significantly better mental health but significantly worse physical well-being. Liver diseases differ in their form of impaired QoL. In HCV, this impairment might not always return to normal after treatment-induced viral clearance. This may suggest that HCV either may not be involved in QoL impairment or may induce a process which persists after viral clearance in some patients. [ABSTRACT FROM AUTHOR]

Background: The ‘Jack Jumper Ant’ (JJA; Myrmecia pilosula species complex) is the major cause of ant sting anaphylaxis in Australia. Our aims were to determine the allergenicity of previously described venom peptides in their native forms, identify additional allergens and if necessary, update nomenclature used to describe the allergens according to International Union of Immunological Societies criteria. Methods: Various polyacrylamide gel electrophoresis methods were used to separate JJA venom. Gel resolved venom was Western-blotted and probed with individual sera taken from patients with a history of JJA sting anaphylaxis and immunoglobulin E radioallergosorbent test (IgE RAST) tracer uptakes of >1% to whole venom. Results: Of 67 available sera, 54 had RAST uptakes >1%. Thirteen IgE binding bands were identified using these sera. Pilosulin 3, [Ile5]pilosulin 1, and pilosulin 4.1 were recognized by 42 (78%), 18 (33%) and nine (17%) of the 54 sera that were tested. Immunoglobulin E-binding proteins with estimated molecular masses of 6.6, 22.8, 25.6, 30.4, 32.1, 34.4 and 89.8 kDa were each recognized by three or more individual sera. Two of these (25.6 and 89.8 kDa) were recognized by 46% and 37% of sera, respectively. Conclusion: Nomenclature used to describe JJA venom allergens has been revised. Pilosulin 3 (Myr p 2) is the only major allergen, whilst [Ile5]pilosulin 1 (Myr p 1), and pilosulin 4.1 (Myr p 3) are minor allergens. There are an additional five IgE-binding proteins that require further characterization before they can be named as allergens. These findings provide a framework for standardizing venom extracts for diagnosis and immunotherapy. [ABSTRACT FROM AUTHOR]

Objective: To identify frequently hospitalized patients by using the outcome and severity measure Health of the Nation Outcome Scales (HoNOS) in combination with the International Classification of Diseases (ICD)-10 in patients consecutively admitted to a psychiatric hospital. Method: All full-time in-patients and all day-hospital patients were considered. Frequently hospitalized patients were defined as those with 10 or more hospitalizations. Results: The total HoNOS score at admission was found valid to discriminate between frequently and non-frequently hospitalized patients as well as in ranking the ICD-10 diagnosis by severity of symptoms and social problems. Frequently hospitalized patients were predominantly found within the diagnoses of schizophrenia and bipolar affective disorders. In these groups, high HoNOS scores were significantly associated with a longer stay in hospital. Improvement during hospitalization as measured by the HoNOS was significantly better for bipolar than for schizophrenic patients. Conclusion: HoNOS was found to be a clinically relevant supplement to ICD-10 in identifying frequently hospitalized patients. [ABSTRACT FROM AUTHOR]

The article reviews the book "Behavior and Medicine," edited by Danny Wedding and Margaret L. Stuber.

An abstract of the article "Chaotic Flow Dynamics Investigated by 3D MRI and CFD Analysis," by M. Wiese and colleagues is presented.

Muscle wasting represents a constant pathological feature of common chronic gastrointestinal diseases, including liver cirrhosis (LC), inflammatory bowel diseases (IBD), chronic pancreatitis (CP) and pancreatic cancer (PC), and is associated with increased morbidity and mortality. Recent clinical and experimental studies point to the existence of a gut-skeletal muscle axis that is constituted by specific gut-derived mediators which activate pro- and anti-sarcopenic signalling pathways in skeletal muscle cells. A pathophysiological link between both organs is also provided by low-grade systemic inflammation. Animal models of LC, IBD, CP and PC represent an important resource for mechanistic and preclinical studies on disease-associated muscle wasting. They are also required to test and validate specific anti-sarcopenic therapies prior to clinical application. In this article, we review frequently used rodent models of muscle wasting in the context of chronic gastrointestinal diseases, survey their specific advantages and limitations and discuss possibilities for further research activities in the field. We conclude that animal models of LC-, IBD- and PC-associated sarcopenia are an essential supplement to clinical studies because they may provide additional mechanistic insights and help to identify molecular targets for therapeutic interventions in humans., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)