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Competing Interests: Disclosures None of the authors reported any disclosures.

Both the 2022 WHO HAEM5 and the International Consensus Classification of lymphoma have refined the way we now approach high-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements moving the previous generation of classification a step forward. The unifying biology of MYC/BCL2 tumours has been clearer and their inferior prognosis confirmed compared to those with morphological similarities but lacking the classifying cytogenetic abnormalities. FISH testing has largely become population based and we have learnt much from this. We can readily define molecular categories and apply these widely to clinical practice. Uncertainty has however been shed upon the place of double MYC/BCL6 translocations in defining a common disease group. We have enhanced knowledge of outcomes and the role of therapy intensification to overcome chemotherapy resistance. For those patients failed by initial induction chemotherapy, immunotherapy approaches, including CAR-T therapies, are improving outcomes. Novel inhibitors, targeting dysregulated oncogenic proteins are being explored at pace. The rare, but difficult, diagnostic classification HGBL (NOS) remains a diagnosis of exclusion with limited data on an optimal clinical approach. The days of talking loosely of double and triple hit lymphoma are numbered as this review synergises the current data on biology, prognosis, and therapies in HGBL., (Copyright © 2024 American Society of Hematology.)

Intertidal artificial habitats are proliferating, but are generally simpler in structure and host lower biodiversity than natural rocky reefs. Eco-engineering aims to enhance the biodiversity of coastal infrastructure, often through physical structural modifications that mimic topographic properties of natural shores. Relationships between biotic assemblages and structural properties of natural and artificial reefs have been extensively studied at sampling scales of up to 1 m 2 . But evidence that quantified local structural variation has an appreciable influence on biotic assemblages, at a shore-wide scale across regional environmental gradients, is lacking. Here we addressed this knowledge gap with an observational study at 32 natural and artificial intertidal reef sites in Wales, UK. We used multivariate community analysis and permutation tests to examine associations between local physical structure, regional environmental variables and sessile biotic assemblages. A potential influence of local habitat structure on assemblage composition was evident across regional-scale environmental gradients. Compared to natural sites, artificial reefs had lower taxonomic richness, distinct and more variable assemblage composition, and different physical structure. After removing the effect of habitat (natural or artificial), canonical correspondence analysis showed that environmental variables (wave exposure, sea surface temperature and salinity variation), along with two metrics of physical structure (standard deviation in log-transformed detrended roughness and skewness of surface verticality, both at 0.5 m scale), explained 40 % of the variation in assemblage composition among sites. The two structural metrics independently explained 14.5 % of the variation. Associations identified between individual taxa and environmental variables indicated that sites with a higher proportion of horizontal surfaces hosted more canopy macroalgae, which in turn support other algae and invertebrates. Our findings provide evidence to inform scaling-up of structural eco-engineering interventions from experimental contexts to enhance the biodiversity of coastal infrastructure across regional extents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Plastic pollution and climate change have commonly been treated as two separate issues and sometimes are even seen as competing. Here we present an alternative view that these two issues are fundamentally linked. Primarily, we explore how plastic contributes to greenhouse gas (GHG) emissions from the beginning to the end of its life cycle. Secondly, we show that more extreme weather and floods associated with climate change, will exacerbate the spread of plastic in the natural environment. Finally, both issues occur throughout the marine environment, and we show that ecosystems and species can be particularly vulnerable to both, such as coral reefs that face disease spread through plastic pollution and climate-driven increased global bleaching events. A Web of Science search showed climate change and plastic pollution studies in the ocean are often siloed, with only 0.4% of the articles examining both stressors simultaneously. We also identified a lack of regional and industry-specific life cycle analysis data for comparisons in relative GHG contributions by materials and products. Overall, we suggest that rather than debate over the relative importance of climate change or marine plastic pollution, a more productive course would be to determine the linking factors between the two and identify solutions to combat both crises., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Canopy-forming macroalgae are known to act as ecosystem engineers, altering the physical parameters of the local environment, and as a result, driving changes in local biodiversity. Although a large body of evidence exists regarding macroalgal canopies on intertidal rocky shores, little is known regarding attached perennial species in soft sediment environments. The aim of this study was to assess whether the presence of an Ascophyllum nodosum canopy altered physical parameters, leading to the formation of different environmental conditions in the areas around the canopy and whether this led to changes in the local community. Sediment cores were taken in canopy-present and canopy-absent treatments at four sites over four sampling periods covering winter (November and January) through to spring (March and May) to assess modification of seven physical parameters: particle size, sand/silt/clay content, chlorophyll a, organic carbon, pore water content and temperature, as well as for macrofaunal diversity. Results revealed significant differences between treatments for all variables with the exception of clay content. Areas below the canopy were dominated by a high abundance of opportunistic species indicating a more disturbed environment, with increased levels of organic enrichment, anoxia and scouring found to be the principal sources of physical disturbance. In conclusion, differences in abiotic parameters between canopy and non-canopy areas in soft-sediment environments were driven both directly and indirectly by the presence of the algal canopy. This facilitated an alternative community composition that enhanced biodiversity within algal-sediment shores., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Anomalous left main coronary artery is rare. We present four cases where anomalous left main coronary artery was diagnosed during emergent cardiac catheterization for ST elevation myocardial infarction. Procedural characteristics, technical challenges, and relevant literature are discussed., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Contingency plans are essential in guiding the response to marine oil spills. However, they are written before the pollution event occurs so must contain some degree of assumption and prediction and hence may be unsuitable for a real incident when it occurs. The use of Bayesian networks in ecology, environmental management, oil spill contingency planning and post-incident analysis is reviewed and analysed to establish their suitability for use as real-time environmental decision support systems during an oil spill response. It is demonstrated that Bayesian networks are appropriate for facilitating the re-assessment and re-validation of contingency plans following pollutant release, thus helping ensure that the optimum response strategy is adopted. This can minimise the possibility of sub-optimal response strategies causing additional environmental and socioeconomic damage beyond the original pollution event., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A common cause for loss of a deep inferior epigastric perforator (DIEP) flap is venous congestion secondary to inadequate outflow via the deep perforating vessels. Further anastomosis of the superficial venous system provides effective outflow and salvage of the congested DIEP. Multiple methods have been described requiring dissection of additional recipient venous systems or around the perforating vessels in order to provide a vein onto which the superficial system may be anastomosed. These are potentially associated with increased morbidity and risk of damage to the pedicle. We describe an alternative technique of harvesting an additional length of deep inferior epigastric pedicle cranial to the perforator onto which an anastomosis may be performed. This avoids the need for additional dissection of recipient vessels or further handling of the perforator, its venae comitantes and the main pedicle of the flap thus reducing the risk of damage., (Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The B-cell receptor (BCR) is a key survival molecule for normal B cells and for most B-cell malignancies. Recombinatorial and mutational patterns in the clonal immunoglobulin (Ig) of chronic lymphocytic leukemia (CLL) have revealed 2 major IgMD-expressing subsets and an isotype-switched variant, each developing from distinct B-cell populations. Tracking of conserved stereotypic features of Ig variable regions characteristic of U-CLL indicate circulating naive B cells as the likely cells of origin. In CLL, engagement of the BCR by antigen occurs in vivo, leading to down-regulated expression and to an unanticipated modulation of glycosylation of surface IgM, visible in blood cells, especially in U-CLL. Modulated glycoforms of sIgM are signal competent and could bind to environmental lectins. U-CLL cases express more sIgM and have increased signal competence, linking differential signaling responses to clinical behavior. Mapping of BCR signaling pathways identifies targets for blockade, aimed to deprive CLL cells of survival and proliferative signals. New inhibitors of BCR signaling appear to have clinical activity. In this Perspective, we discuss the functional significance of the BCR in CLL, and we describe strategies to target BCR signaling as an emerging therapeutic approach.

The anti-CD20 mAb rituximab is central to the treatment of B-cell malignancies, but resistance remains a significant problem. We recently reported that resistance could be explained, in part, by internalization of rituximab (type I anti-CD20) from the surface of certain B-cell malignancies, thus limiting engagement of natural effectors and increasing mAb consumption. Internalization of rituximab was most evident in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), but the extent of internalization was heterogeneous within each disease. Here, we show that the inhibitory FcγRIIb on target B cells promotes this process and is largely responsible for the observed heterogeneity across a range of B-cell malignancies. Internalization correlated strongly with FcγRIIb expression on normal and malignant B cells, and resulted in reduced macrophage phagocytosis of mAb-coated targets. Furthermore, transfection of FcγRIIb into FcγRIIb negative Ramos cells increased internalization of rituximab in a dose-dependent manner. Target-cell FcγRIIb promoted rituximab internalization in a cis fashion and was independent of FcγRIIb on neighboring cells. It became phosphorylated and internalized along with CD20:anti-CD20 complexes before lysosomal degradation. In MCL patients, high FcγRIIb expression predicted less durable responses after rituximab-containing regimens. Therefore, target-cell FcγRIIb provides a potential biomarker of response to type I anti-CD20 mAb.

Objective: To determine the incidence of acute mountain sickness (AMS), the frequency of summiting success, and the factors that affect these in trekkers on Kilimanjaro, one of the world's most summitted high-altitude peaks., Methods: The study group comprised 312 trekkers attempting Mt Kilimanjaro summit by the Marango Route. Trekkers ascended over 4 or 5 days along a fixed ascent profile, stopping at 3 huts on ascent (2700 m, 3700 m, and 4700 m) before attempting the summit. Researchers were stationed at each hut for 16 days. Each night we measured heart rate, respiratory rate, blood pressure, oxygen saturation, and Lake Louise Score. We recorded the highest altitude that trekkers reached on the mountain., Results: Of 181 complete sets of data, 111 (61%) trekkers reached the summit, and 139 (77%) developed AMS. Physiological results were not related to summit success. The incidence of AMS and summiting success were similar in those on the 4- or 5-day route. Trekkers on the 5-day route who used acetazolamide were less likely to develop AMS and more likely to summit than were those not taking acetazolamide (P = <.05); this difference was not present with trekkers on the 4-day route., Conclusions: The risk of developing AMS is high on Mt Kilimanjaro. Although taking an extra day to acclimatize with the use of acetazolamide did provide some protection against AMS, ideally trekkers need a more gradual route profile for climbing this mountain.

The discovery by McIntire and Faulk of masked autoantibodies calls into question the mechanisms of self recognition that exist in the human body. Their finding is reviewed in relation to three other facets of the interaction of humans with the foreign agencies with which they come in contact, innate immunity, microchimaerism and communicable disease-causing infections. It is concluded that the capacity to respond to foreign agencies may not primarily be defensive and that self recognition is probably an active process rather than dependent on elimination of self reactive capacity.

Concentrations of free polyamines were investigated in Trypanosoma granulosum cultured in a semidefined medium containing traces of polyamines. Spermidine content peaked in early logarithmic growth while putrescine was not detectable. Unlike African trypanosomes and Leishmania, spermine was measured at equivalent amounts to spermidine in mid to late logarithmic stage cells. Addition of d,l-alpha-difluoromethylornithine to cultures did not decrease polyamine content nor was ornithine decarboxylase activity detected. In contrast, incubation of parasites with tritiated putrescine showed rapid uptake and subsequent conversion to spermidine and spermine. At late logarithmic growth, parasites contained glutathione (77% of total sulphydryl groups) and ovothiol A as major low molecular mass thiols with glutathionylpolyamine conjugates undetectable. However, the addition of exogenous putrescine elevated trypanothione and glutathionylspermidine content to 48% of total sulphydryl groups. Correspondingly, the addition of exogenous cadaverine increased homotrypanothione content. This first report of polyamines and low molecular mass thiols in Trypanosoma granulosum indicates intriguing similarities with the metabolism of the human pathogen Trypanosoma cruzi., (Copyright 2001 Academic Press.)

A subjective analysis of information available on the Internet to those working in forensic medicine medicine was performed. Internet web sites addressing forensic pathology, forensic science, anthropology, entomology, law enforcement, societies and journals were assessed. Ease of access, presentation, structure, specialization, links and popularity were reviewed. Each individual site assessed was graded out of 100 and ranked, by subject, to provide the reader with a generalized guide to what the authors considered was useful and/or interesting forensic sites on the internet. The need for a regulatory body for forensic Internet resources is discussed.

The British Thoracic Society (BTS) guidelines for the treatment of community-acquired pneumonia recommend initial therapy with a betalactam antibiotic, with the addition of erythromycin if there are features of an atypical pneumonia. To see if these guidelines were being followed, a prospective study was undertaken of all adult patients admitted to hospital over a 3-month period who were given erythromycin for a community-acquired lower respiratory tract infection. Erythromycin was given to 62 patients who could be fully assessed. Continued prescription of erythromycin was justified in 10 (16%)--two patients with penicillin allergy, two with M. catarrhalis infection and one patient with legionnaires disease. Five patients had infections severe enough on admission to warrant combined therapy in line with the BTS recommendations. Five patients had erythromycin stopped on day 2. Erythromycin was prescribed on admission and continued unnecessarily in 47/62 patients, showing that the BTS recommendations are not being followed correctly.

The binding, internalization and recycling of the plant toxin ricin, was studied using electron microscopy and biochemical techniques. For the electron microscope study, ricin was visualized using a gold-labeled second antibody, in the cells of the EJ human bladder carcinoma line growing in monolayer culture. The labeled antibody/toxin complex was found to enter the cell in coated pits and to accumulate in endosomes and to a lesser extent in vesicles associated with the Golgi system. The complex recycled to the cell surface partly in uncoated vesicles, but largely in multivesicular bodies which appeared to exocytose their contents to the extracellular space. Twenty hours after the initial contact with ricin as much as 50% of the cellular label was found on the cell surface mainly associated with shed vesicles. When cells were treated with unlabeled ricin holotoxin and then after 20 h stained post-fixation, ricin molecules, partly associated with vesicles, were present on the cell surface. Biochemical studies showed that ricin was internalized by cells and then released in an intact form to the extracellular space. It was found that less than 10% of the released material had been degraded during its passage through the cells, which is in accord with the low level of label found in the lysosomal system during the morphological study.

50 cases of primary acute lymphoid leukaemia (A.L.L.) were analysed for the presence of T and B membrane markers on bone-marrow and/or peripheral-blood cells. 26% of cases were predominantly T-cell in type, 4% were B, the remaining 70%, without detectable membrane markers, were classified as "null" cell A.L.L. Of particular interest is the correlation between this immunological classification and the prognosis, since T-cell and B-cell A.L.L. were associated with a poorer prognosis than null-cell A.L.L. in terms of both median length of first complete remission and median survival. With one exception the T-cell cases were, according to the W.H.O. classification, of either the prolymphocytic or macrolymphoblastic type of A.L.L. and were more extensive than the comparable null-cell A.L.L. In contrast, cases of the W.H.O. prolymphoblastic and microlymphoblastic types were all found to be null-cell A.L.L. and were associated with the worst and best prognosis respectively. The correlation found between the immunological classification of A.L.L. and the prognosis means that patients with a poor prognosis can be selected for more intensive therapy.

Tumour capsules may arise as the result of a modified wound healing response, consequent upon disturbance of the normal tissue architecture caused by an expanding tumour.

309 women whose menstruation was delayed by 3-35 days were treated with intrauterine or vaginal prostaglandins. Of 275 confirmed pregnancies, 229 were successfully terminated without further abortifacient therapy. A successful outcome was often associated with episodes of vomiting, diarrhoea, and uterine cramps in the 24 hours after prostaglandin administration, but the incidence was related to prostaglandin dosage and gastrointestinal side-effects were more common after vaginal administration. The best results were achieved by the analogue 16:16 dimethyl P.G.E2 as a vaginal pessary. 14 patients (6.1%) required uterine curettage for escessive or prolonged bleeding, while 2 patients required blood transfusion. One patient, who had an intrauterine contraceptive device left in situ during treatment, developed acute pelvic sepsis. No deleterious side-effects occurred in 34 patients who were subsequently proven not to be pregnant at the time of treatment. Treatment by intrauterine or vaginal prostaglandins offers promise as a method of pregnancy termination which avoids much of the physical and emotional trauma associated with surgical termination, and has the advantage of not requiring hospital admission in the majority of cases. The present study shows the safety of the method, and its potential as a self-administration technique.