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A computational aeroelastic model is presented for a cantilevered plate rotated from a position with the clamped edge normal to the flow (0 deg) to where the clamped edge is aligned with the flow (90 deg) using a new inextensible plate theory. A large-amplitude limit-cycle oscillation has been observed beyond the linear flutter speed in both the computations and in a wind-tunnel experiment. The computations and experiments for the limit-cycle oscillation response of the several yaw ed plate aeroelastic models show that the inextensible plate theory produces results in good agreement with the measurements. Also, a comparison with results obtained using von Karman's nonlinear plate theory has been made. [ABSTRACT FROM AUTHOR]

The article presents information on the updated set of guidelines prepared for the British Association of Dermatologists (BAD) for 2014. It states that the guidelines offers an up-to-date information for the management of infectious cutaneous warts due to papillomavirus infection. It stresses the morphological varieties of warts that turn to lesions such as seborrhoeic keratoses or seborrhoeic warts.

The aeroelastic stability of cantilevered plates with their clamped edge oriented both parallel and normal to subsonic flow is a classical fluid–structure interaction problem. When the clamped edge is parallel to the flow the system loses stability in a coupled bending and torsion motion known as wing flutter. When the clamped edge is normal to the flow the instability is exclusively bending and is referred to as flapping flag flutter. This paper explores the stability of plates during the transition between these classic aeroelastic configurations. The aeroelastic model couples a classical beam structural model to a three-dimensional vortex lattice aerodynamic model. The aeroelastic stability is evaluated in the frequency domain and the flutter boundary is presented as the plate is rotated from the flapping flag to the wing configuration. The transition between the flag-like and wing-like instability is often abrupt and the yaw angle of the flow for the transition is dependent on the relative spacing of the first torsion and second bending natural frequencies. This paper also includes ground vibration and aeroelastic experiments carried out in the Duke University Wind Tunnel that confirm the theoretical predictions. [ABSTRACT FROM AUTHOR]

Offering feed supplements to grazing dairy cows results in substitution of pasture; however, previous data indicate that the time at which concentrate supplements are offered might affect the level of substitution. These data indicated that cows grazed more intensely presunset, regardless of the amount of supplement offered. It was, therefore, hypothesized that substitution rate would be less, and response to supplement greater if cows received their supplement at the p.m. rather than the a.m. milking. Forty-eight multiparous, non-pregnant, Holstein-Friesian cows, approximately 60 d in milk, were randomly allocated to 1 of 3 treatments in an incomplete crossover arrangement. Treatments were pasture only, pasture + 3 kg of concentrate supplement dry matter (DM) offered during the a.m. milking (AM-SUP), and pasture + 3 kg of concentrate supplement DM offered during the p.m. milking (PM-SUP). Time spent grazing and calculated pasture DM intake did not differ between the AM-SUP and PM-SUP cows. However, a tendency (0.18 kg of milk/kg of concentrate DM) was observed for an increased marginal milk response (kg of milk/kg of DM supplement) for the AM-SUP cows when compared with PM-SUP cows. Irrespective of when supplements were offered, supplementation reduced total grazing time by a similar amount, and the reduction in time spent grazing was evident throughout the day. Cows in the PM-SUP group ruminated for longer and cows in the AM-SUP group spent more time idle compared with the pasture only groups. Cows in the AM-SUP group grazed for less time during the major a.m. grazing bout following a.m. milking compared with PM-SUP cows; in comparison, the major p.m. grazing bout following p.m. milking was unaffected by supplementation. The results indicated possible improvements in marginal milk response to supplements from altering the timing of delivery. [ABSTRACT FROM AUTHOR]

Abstract: This paper explores cantilevered beam flutter for both clamped and pinned leading edge boundary conditions. Specifically, a three-dimensional vortex lattice panel method is coupled with a classical Lagrangian one-dimensional beam structural model to predict the linear flutter boundary for finite size rectangular plates. The paper explores the change in flutter characteristics as a function of the fluid to structure mass ratio and the structural aspect ratio. The paper also presents an exploration of the non-monotonic transition in flutter velocity between the pinned-free and clamped-free boundary conditions which is modeled using a leading edge torsional spring. The theoretical results are compared to vibration and aeroelastic test results collected in the Duke University wind tunnel as well as previous theoretical and experimental results for the leading edge clamped configuration. The aeroelastic experiments confirmed the validity of the three-dimensional vortex lattice aerodynamic model over a subset of mass ratios. [Copyright &y& Elsevier]

. Sattianayagam PT, Gibbs SDJ, Rowczenio D, Pinney JH, Wechalekar AD, Gilbertson JA, Hawkins PN, Lachmann HJ, Gillmore JD (University College London Medical School, London, UK). Hereditary lysozyme amyloidosis - phenotypic heterogeneity and the role of solid organ transplantation. J Intern Med 2012; 272: 36-44. Objectives. Lysozyme amyloidosis (ALys) is a form of hereditary systemic non-neuropathic amyloidosis, which is inherited in an autosomal dominant fashion. Lysozyme, which is the amyloidogenic precursor protein in ALys, is a ubiquitous bacteriolytic enzyme synthesized by hepatocytes, polymorphs and macrophages. The aim of this study is to describe the phenotype and outcome of patients with ALys including the role of solid organ transplantation. Design. Retrospective evaluation of patients with ALys. Setting. UK National Amyloidosis Centre. Patients. All 16 patients with ALys followed at the centre. Results. A family history of amyloidosis was present in every affected individual. Although the phenotype was broadly similar amongst those from the same kindred, there were marked phenotypic differences between kindreds who possessed the same amyloidogenic mutation. Symptomatic gastrointestinal (GI) amyloid was prevalent, and macroscopically visible amyloidotic lesions were present in nine of 10 patients who underwent GI endoscopy. All symptomatic ALys individuals had hepatic amyloid. Four patients received orthotopic liver transplants (OLT), three for spontaneous hepatic rupture and one case, who had extensive hepatic amyloid and a strong family history of hepatic rupture, pre-emptively. All of the liver grafts were functioning at censor 1.7, 5.8, 9.0 and 11.0 years after OLT. Five patients had progressive amyloidotic renal dysfunction culminating in end-stage renal failure, three of whom underwent renal transplantation (RTx). There was no evidence of renal allograft dysfunction at censor 6.6, 1.8 and 0.8 years after RTx. Conclusions. Lysozyme amyloidosis is a disease of the GI tract, liver and kidneys, which has a slow natural history. There was a clear family history in all cases within this cohort, demonstrating a high clinical penetrance in the presence of an amyloidogenic lysozyme mutation. There is currently no amyloid-specific therapy for the condition which is managed symptomatically. OLT and RTx appear to be successful treatments for patients with liver rupture or end-stage renal disease, respectively, with excellent outcomes in terms of medium-term graft function and patient survival. [ABSTRACT FROM AUTHOR]

Morphing-wing research has garnered much attention in the aerospace community over the last decade, and the folding wing is a promising concept that can improve aircraft performance over multiple types of missions. Several high-fidelity analyses of folding-wing aeroelastic stability have been published, but most analyses are specific to certain wing planforms or a fixed number of wing segments. This paper presents a general aeroelastic model that predicts the flutter speed and flutter frequency of a folding wing with simplified geometry but with an arbitrary number of wing segments. The beam-theory structural model and the strip-theory unsteady aerodynamic model are coupled using Lagrange's equations. Three experimental models are constructed, and flutter tests are performed over a wide range of fold angles. The theoretical predictions for flutter speeds are within 10% of experimentally measured values for most configurations. In general, the results show that the essential physics of the problem is captured by the present first-principles model. Furthermore, data show that increasing the fold angle causes up to 30% increase in flutter speed, which has applications in extending the flutter boundaries of morphing aircraft. [ABSTRACT FROM AUTHOR]

Abstract: Children with cerebral palsy (CP) often experience significant problems supporting their bodyweight (BW) and decelerating the downward velocity of the centre of mass (CoM) in late stance. This is seen as a decreased second peak of vertical ground reaction force (GRF) nominated FZ2. This study categorises gait data by the degree of reduced FZ2. Kinetic data were analysed from a CP database. Data from 129 patients, able to walk barefoot unaided, were investigated. Of these, 84 had kinetic data, 59 diplegics (both legs) and 15 hemiplegics (affected leg only), thus providing data from 133 legs. A reduced FZ2 was observed in 116 legs (87%). Of the 133 legs, 44% failed to generate FZ2 >BW. By including the Type 2 data this figure rises to, a staggering 66% who are having difficulty supporting BW at this stage of the stance phase. Only 12% of the legs showed a normal pattern (FZ2 approximately equal to FZ1). In conclusion, the majority of CP children referred to the gait laboratory exhibited some degree of reduced FZ2 and can be categorised as having a ‘Ben Lomonding’ gait pattern. ‘Ben Lomonding,’ is the term used to describe this phenomenon of reduced FZ2, as the shape of the GRF graph resembles the shape of the Scottish mountain, Ben Lomond, which has two peaks, the second peak being much smaller than the first. Crucially, clinicians should be aware that nearly half of the CP children in this study were in difficulty supporting their BW in late stance and must use compensatory mechanisms to prevent collapse of the affected limb. [Copyright &y& Elsevier]

BACKGROUND: In gait analysis, calculation of the ankle joint centre is a difficult task. The conventional way to calculate the ankle joint centre is using the Vicon Plug-in-Gait model. The present study proposes a new model, which calculates the joint centre from two markers positioned over the medial and lateral malleoli (i.e. Two-marker-model). METHODS: In order to compare the proposed model with Plug-in-Gait model, gait data from healthy and patient subjects were captured using a motion capture system. The ankle joint centres were calculated by the two models. A test-retest experiment was carried out to check reliability and repeatability for Two-marker-model. FINDINGS: Two ankle joint centres produced by two models were significantly different. The distances between two ankle joint centres were approximately 16.8 (mm), and the differences in the posterior-anterior, medial-lateral and inferior-superior directions were approximately 6.3, 7.7 and 8.2 (mm). Further error analysis highlighted that the probability of producing errors in Two-marker-model is lower than that in Plug-in-Gait model due to the Two-marker-model's simple and reliable marker positioning. The reliability and repeatability coefficients for the new model were greater than 0.9. INTERPRETATION: In principle, the Plug-in-Gait model is more likely to produce errors than the Two-marker-model, because the former employs multiple markers from the pelvis to calf to define the ankle joint centre with marker positions being very user-dependent. The results suggest that the Two-marker-model can be considered an alternative to Plug-in-Gait model for calculating ankle joint centre. [ABSTRACT FROM AUTHOR]

Background People with intellectual disabilities (ID) have higher levels of health needs compared with the general population, many of which are unrecognised and unmet. While there has been interest and research into the primary health provision for this group, there has been a more limited focus on addressing their care received in general hospitals. Access to health care has predominated in the literature, with less attention being paid to the experiences of people with ID as users of general hospital care. Method A qualitative focus group methodology was used. Eleven adults with ID, nine parents and five paid carers of adults with ID participated. The focus groups were audiotaped and transcriptions were analysed using principles of grounded theory. Results The analysed data highlighted key themes identified from the experiences of participants. These were the interrelated issues of feelings, particularly anxiety and fear, communication and behaviour problems; the practicalities of being in or attending hospitals, including the role played by carers; and issues around perceived discrimination and negative comments. Conclusions The experiences of participants in this study concur with and add to concern expressed in recent reports and published research. Wide ranging implications are discussed for further research, wider policy development, clinical practice, local health service provision and education of health professionals. [ABSTRACT FROM AUTHOR]

Explore whether product launch strategy can be elucidated by type and timing of industry-sponsored publications. Our PubMed search strategy successfully identified industry-sponsored research, and we intend to use the strategy to develop a larger sample of cases. [Extracted from the article]

Background Chronic wounds represent a major problem to our society. Therefore, advanced wound-healing strategies for the treatment of these wounds are expanding into the field of tissue engineering. Objectives To develop a novel tissue-engineered, autologous, full-thickness skin substitute of entirely human origin and to determine its ability to heal chronic wounds. Methods Skin substitutes (fully differentiated epidermis on fibroblast-populated human dermis) were constructed from 3-mm punch biopsies isolated from patients to be treated. Acellular allodermis was used as a dermal matrix. After a prior 5-day vacuum-assisted closure therapy to prepare the wound bed, skin substitutes were applied in a simple one-step surgical procedure to 19 long-standing recalcitrant leg ulcers (14 patients; ulcer duration 0·5–50 years). Results The success rate in culturing biopsies was 97%. The skin substitute visibly resembled an autograft. Eleven of the 19 ulcers (size 1–10 cm2) healed within 8 weeks after a single application of the skin substitute. The other eight larger (60–150 cm2) and/or complicated ulcers healed completely ( n = 5) or continued to decrease substantially in size ( n = 3) after the 8-week follow-up period. Wound healing occurred by direct take of the skin substitute ( n = 12) and/or stimulation of granulation tissue/epithelialization ( n = 7). Skin substitutes were very well tolerated and pain relief was immediate after application. Conclusions Application of this novel skin substitute provides a promising new therapy for healing chronic wounds resistant to conventional therapies. [ABSTRACT FROM AUTHOR]

Cardiac involvement is not regarded as a feature of Henoch-Schönlein purpura (HSP). We report a patient with HSP who developed significant cardiac symptoms, which resolved with immunosuppression. We review previous cases of HSP with cardiac features, none of which showed a response to treatment, and discuss evidence that cardiac involvement is more common than recognized. The implications for investigation and treatment of this condition are discussed. [ABSTRACT FROM AUTHOR]

This study describes a case of extra-nodal marginal zone lymphoma presenting in skeletal muscle and recurring on multiple occasions in the same tissue at other sites. In this case, 18 F-fluoro-deoxy-glucose positron emission tomography scanning was the most useful surveillance modality. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary Background There is little information on specific interactions between dermal fibroblasts and epidermal keratinocytes. The use of engineered skin equivalents consisting of organotypic cocultures of keratinocytes and fibroblasts offers an attractive approach for such studies. Objectives To examine the role fibroblasts play in generation and maintenance of reconstructed epidermis. Methods Human keratinocytes were seeded on collagen matrices populated with increasing numbers of fibroblasts and cultured for 2 weeks at the air–liquid interface. Results In the absence of fibroblasts, stratified epidermis with only three or four viable cell layers was formed. In the presence of fibroblasts, keratinocyte proliferation was stimulated and epidermal morphology was improved. Epidermal morphogenesis was also markedly improved in epidermis generated in organotypic keratinocyte monocultures grown in medium derived from dermal equivalents or from organotypic keratinocyte–fibroblast cocultures. These observations clearly indicate the proliferation-stimulating activity of soluble factors released from fibroblasts. Under all experimental conditions, onset of keratinocyte differentiation was shown by the expression of keratin 10 in all suprabasal cell layers. With increasing numbers of fibroblasts incorporated into the collagen matrix, the expression of markers associated with keratinocyte activation, e.g. keratins 6, 16 and 17 and the cornified envelope precursor SKALP decreased, and involucrin localization shifted toward the granulosum layer. This fibroblast-mediated effect was even more pronounced when the fibroblasts were precultured in the collagen matrices for 1 week instead of overnight. The basement membrane proteins collagen VII and laminin 5 were present at the epithelial–matrix border. The expression of integrin α6β4 and of E-cadherin was comparable with that seen in native skin and was not significantly modulated by fibroblasts.... [ABSTRACT FROM AUTHOR]

Investigates the effectiveness of topical immunotherapy with contact sensitizers for viral warts. Treatments of cutaneous warts; Comparison of efficacy between placebo and dinitrochlorobenzene; Side effects of dinitrochlorobenzene.

Chronic alcohol-dependent patients have reduced brain volumes and concomitant neurobehavioral deficits that may recover during abstinence. In 10 chronic alcoholic patients, using localized proton magnetic resonance spectroscopy, we found reliable increases during the first 3-4 weeks of abstinence in the concentrations within the superior cerebellar vermis of choline (Cho)-containing compounds relative to the neuronal marker, N-acetylaspartate (NAA). Lesser changes were observed following 1 month of abstinence, and in one of the patients studied longitudinally over 3 months, a marked reduction in the Cho/NAA ratio was associated with relapse. After detoxification, the Cho/NAA ratio correlated with a composite clinical impression of brain functions. The lowest Cho/NAA was observed in a patient with persisting alcoholic dementia, in striking contrast to reduced relative concentrations of NAA reported in dementia of the Alzheimer's type. Possible molecular explanations for these brain metabolic changes are discussed. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article regarding primary care management for melanoma patients.

Two unrelated adult patients are described who both developed an exanthem with the characteristic morphology and distribution of the Gianotti–Crosti syndrome. The literature of adult cases of Gianotti–Crosti syndrome is reviewed with the suggestion that the syndrome may not be as uncommon as previously supposed. [ABSTRACT FROM AUTHOR]

The article provides an answer to a question concerning the warts that occur as a result of the human papilloma virus.

BACKGROUND Transthyretin amyloid cardiomyopathy is characterized by the deposition of mis, folded monomeric transthyretin (TTR) in the heart. Acoramidis is a high-affinity TTR stabilizer that acts to inhibit dissociation of tetrameric TTR and leads to more than 90% stabilization across the dosing interval as measured ex vivo. METHODS In this phase 3, double-blind trial, we randomly assigned patients with transthyretin amyloid cardiomyopathy in a 2:1 ratio to receive acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo for 30 months. Efficacy was assessed in the patients who had an estimated glomerular filtration rate of at least 30 ml per minute per 1.73 m.2 of body-surface area. The four-step primary hierarchical analysis included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro-B-type natriuretic peptide INT-proBNP) level, and the change from baseline in the 6-minute walk distance. We used the Finkelstein-Schoenfeld method to compare all potential pairs of patients within strata to generate a P value. Key secondary outcomes were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire-Overall Summary, and the serum TTR level. RESULTS A total of 632 patients underwent randomization. The primary analysis favored acoramidis over placebo (P<0.001); the corresponding win ratio was 1.8 (95% confidence interval ICI], 1.4 to 2.2), with 63.7% of pairwise comparisons favoring acoramidis and 35.9% favoring placebo. Together, death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons); NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs. 7.0°6). The overall incidence of adverse events was similar in the acoramidis group and the placebo group 98.1% and 97696, respectively); serious adverse events were reported in 54.6% and 64.990 of the patients. CONCLUSIONS In patients with transthyretin amyloid cardiomyopathy, the receipt of acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo. Adverse events were similar in the two groups. (Funded by BridgeBio Pharma; ATTRibute-CM ClinicalTrials.gov number, NCT03860935.). [ABSTRACT FROM AUTHOR]

A response by S. Gibbs, C. S. Kwok, and R. Holland to a letter to the editor on their article regarding the effectiveness of clear duct tape in eradicating common wart in the 2011 issue is presented.

A letter to the editor is presented in response to the article about the study on the safety of renal biopsy in cases of suspected amyloidosis.

Presents a letter to the editor about chronic urticaria responding to subcutaneous heparin sodium.

Comments on a study by Al-Gurairi et. al. on the treatment of viral warts using zinc sulphate published in the 2002 issue of the 'British Journal of Dermatology.' Method used for the collection of samples for clinical trials; Effectiveness of the treatment using zinc.

The article discusses the study which measures the usage of fluorouracil (FU) cream and the experience of patients who uses the cream as treatment. The study involves 112 patients with prescriptions of 5% FU cream to treat skin diseases such as Bowen disease (BD), solar keratosis, and superficial basal cell carcinoma (BCC) wherein the amount of the unused cream were measured. The study suggests that 97% of patients who uses the cream were very satisfied.

Tonic and phasic rapid eye movement ( REM) sleep seem to represent two different brain states exerting different effects on epileptic activity. In particular, interictal spikes are suppressed strongly during phasic REM sleep. The reason for this effect is not understood completely. A different level of synchronization in phasic and tonic REM sleep has been postulated, yet never measured directly. Here we assessed the interictal spike rate across non- REM ( NREM) sleep, phasic and tonic REM sleep in nine patients affected by drug resistant focal epilepsy: five with type II focal cortical dysplasia and four with hippocampal sclerosis. Moreover, we applied different quantitative measures to evaluate the level of synchronization at the local and global scale during phasic and tonic REM sleep. We found a lower spike rate in phasic REM sleep, both within and outside the seizure onset zone. This effect seems to be independent from the histopathological substrate and from the brain region, where epileptic activity is produced (temporal versus extra-temporal). A higher level of synchronization was observed during tonic REM sleep both on a large (global) and small (local) spatial scale. Phasic REM sleep appears to be an interesting model for understanding the mechanisms of suppression of epileptic activity. [ABSTRACT FROM AUTHOR]

A normally fit European resident of East Africa developed a staphylococcal peri-nephric abscess following repeated episodes of furuncular myiasis caused by the tumbu fly, Cordylobia anthropophaga. A few lesions had required surgical intervention and one, presumably the source of sepsis, had become infected. There are very few descriptions in the literature of serious complications of myiasis and this is the first report of peri-nephric abscess from this source. This paper discuses the management of the myiasis and what factors determine the variation in host susceptibility and immune response to the infestation. [ABSTRACT FROM AUTHOR]

In this work, we develop a mathematical formalism based on a 3D in vitro model that is used to simulate the early stages of angiogenesis. The model treats cells as individual entities that are migrating as a result of chemotaxis and durotaxis. The phenotypes used here are endothelial cells that can be distinguished into stalk and tip (leading) cells. The model takes into account the dynamic interaction and interchange between both phenotypes. Next to the cells, the model takes into account several proteins such as vascular endothelial growth factor, delta-like ligand 4, urokinase plasminogen activator and matrix metalloproteinase, which are computed through the solution of a system of reaction-diffusion equations. The method used in the present study is classified into the hybrid approaches. The present study, implemented in three spatial dimensions, demonstrates the feasibility of the approach that is qualitatively confirmed by experimental results. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about the diagnosis and treatment of tungiasis, published in the previous issue.

Fusobacterium necrophorum is infrequently implicated as a pathogenic organism. When pathogenic, the typical clinical presentation is that of pharyngitis, cervical adenopathy, and unilateral thrombophlebitis of the internal jugular vein. Infections caused by Fusobacterium necrophorum within the fields of obstetrics and gynecology have been infrequently reported. We describe a 19-year-old woman who underwent a cesarean delivery complicated by sepsis and purulent uterine necrosis secondary to Fusobacterium necrophorum infection. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the relationship between nitrogen isotopic fractionation (δ15N) and nitrogen-use efficiency (milk nitrogen/nitrogen intake; NUE) in pasture-fed dairy cows supplemented with increasing levels of urea to mimic high rumen degradable protein pastures in spring. Fifteen cows were randomly assigned to freshly cut pasture and either supplemented with 0, 250, or 336 g urea/d. Feed, milk, and plasma were analyzed for δ15N, milk and plasma for urea nitrogen concentration, and plasma for ammonia concentration. Treatment effects were tested using ANOVA and relationships between variables were established by linear regression. Lower dry matter intake (P = 0.002) and milk yield (P = 0.002) occurred with the highest urea supplementation (336 g urea/d) compared with the other two treatments. There was a strong linear relationship between milk δ15N - feed δ15N and NUE: [NUE (%) = 58.9 - 10.17 × milk δ15N - feed δ15N (‹) (r(2) = 0.83, P < 0.001, SE = 1.67)] and between plasma δ15N - feed δ15N and NUE: [NUE (%) = 52.4 - 8.61 × plasma δ15N - feed δ15N (‹) (r² = 0.85, P < 0.001, SE = 1.56)] . This study confirmed the potential use of δ15N to predict NUE in cows consuming different levels of rumen degradable protein. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

Nitrogen (N) deposition and land management practices can have profound impacts on the structure and functioning of alpine ecosystems occupying headwaters of major river systems. Such impacts have the potential to result in loss of N to surface waters and acidification, both of which could have serious consequences for water quality and downstream habitats. We present results from a 6-year study of Calluna-dominated alpine heathland in Scotland, designed to assess the interactive effects of N addition (0 and 50 kg N ha−1 y−l), simulated accidental fire and grazing on soil solution chemistry. Both N addition and to a lesser extent burning had significant effects on soil solution chemistry, whereas grazing had no significant impact. Soil solution nitrate (NO3 −) and ammonium (NH4 +) concentration showed a rapid response to N addition and N addition also resulted in acidification of soil solution. A ‘flush’ of base cations, which normally buffer soil from the acid effects of deposited N, accompanied the excess N released from the soil to soil solution. The N treatment had no effect on dissolved organic carbon (DOC), however, concentrations were significantly (14%) lower at the burned plots. In addition to treatment effects, temporal analysis of data from control plots demonstrated that soil solution chemistry was influenced by extremes in weather conditions. Peak NO3 − concentrations were observed in soil solution following the cold winter of 2000–2001 when there were frequent freeze/thaw events. A large pulse of base cations was lost from the soil following the dry year of 2003. These weather-induced responses potentially exacerbate the treatment effects observed in this study. [ABSTRACT FROM AUTHOR]

BACKGROUND Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition ofamyloid fibrils oflight chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. METHODS We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. RESULTS A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage ofpatients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53 . 3 % vs. 18.1%) (relative risk ratio, 2.9; 9596 confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P=0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.90/0, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7,8% and 4.30/0, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7°/0). Systemic administration-related reactions to daratumumab occurred in 7.3% ofthe patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. CONCLUSIONS Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression, (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.) [ABSTRACT FROM AUTHOR]

Summary Background The basopenia of chronic urticaria relates to histamine releasing autoantibodies in the serum of patients with autoimmune urticaria. This reduction in circulating basophils may be due to active recruitment into weals. If so, it might be expected that numbers in blood would be reduced when urticaria is active and increased after treatment. The primary aim of this study was to look at diurnal variation of basophil numbers in patients with chronic ordinary urticaria (not physical or vasculitic) in relation to disease activity and the effect of treatment with antihistamines and corticosteroids, and to compare the results with healthy controls. A secondary aim was to compare a standard manual counting method with automated basophil counts and to look at numbers of other circulating leucocytes that might be relevant to urticaria pathogenesis. Methods Manual basophil counts using a toluidine blue stain and automated 5-part differentials (Coulter® Gen. S™) were performed at 4-hourly intervals from 08.00 to 20.00 in 10 healthy controls (six women, age 24 to 63 years) and seven chronic urticaria patients (five women, 24 to 50 years). All chronic urticaria patients had severe daily or almost daily urticaria. Only one of six chronic urticaria sera showed in vitro basophil histamine releasing activity. Counts were performed without treatment, after a week of taking loratadine 10 mg daily and after 3 days of adding prednisolone at 0.6 mg/kg/day (maximum 40 mg). Daily urticarial activity scores (UAS) were derived from weal numbers and itch, maximum 7. Results There was no significant overall diurnal variation of basophil numbers in healthy controls or chronic urticaria patients. Mean (SE) manually counted basophil were higher in healthy controls than chronic urticaria (43.4/µL (2.1) vs. 4.4 (0.8), P < 0.001). Basophil counts were reduced in healthy controls on steroids (19.2 (1.9), P < 0.001) but increased in chronic urticaria (8.9... [ABSTRACT FROM AUTHOR]