Molecular and immunologic breakthroughs are transforming the management of thoracic cancer, although advances have not been as marked for malignant pleural mesothelioma where pathologic diagnosis has ...been essentially limited to three histologic subtypes.
A multidisciplinary group (pathologists, molecular biologists, surgeons, radiologists, and oncologists), sponsored by European Network for Rare Adult Solid Cancers/International Association for the Study of Lung Cancer, met in 2018 to critically review the current classification.
Recommendations include: (1) classification should be updated to include architectural patterns and stromal and cytologic features that refine prognostication; (2) subject to data accrual, malignant mesothelioma in situ could be an additional category; (3) grading of epithelioid malignant pleural mesotheliomas should be routinely undertaken; (4) favorable/unfavorable histologic characteristics should be routinely reported; (5) clinically relevant molecular data (programmed death ligand 1, BRCA 1 associated protein 1 BAP1, and cyclin dependent kinase inhibitor 2A) should be incorporated into reports, if undertaken; (6) other molecular data should be accrued as part of future trials; (7) resection specimens (i.e., extended pleurectomy/decortication and extrapleural pneumonectomy) should be pathologically staged with smaller specimens being clinically staged; (8) ideally, at least three separate areas should be sampled from the pleural cavity, including areas of interest identified on pre-surgical imaging; (9) image-acquisition protocols/imaging terminology should be standardized to aid research/refine clinical staging; (10) multidisciplinary tumor boards should include pathologists to ensure appropriate treatment options are considered; (11) all histologic subtypes should be considered potential candidates for chemotherapy; (12) patients with sarcomatoid or biphasic mesothelioma should not be excluded from first-line clinical trials unless there is a compelling reason; (13) tumor subtyping should be further assessed in relation to duration of response to immunotherapy; and (14) systematic screening of all patients for germline mutations is not recommended, in the absence of a family history suspicious for BAP1 syndrome.
These multidisciplinary recommendations for pathology classification and application will allow more informative pathologic reporting and potential risk stratification, to support clinical practice, research investigation and clinical trials.
The use of Cornish’s crime-scripts approach in situational crime prevention grows apace. However, we believe the conceptual foundation of cognitive scripts imported from Abelson and colleagues was ...rather unclear and is too narrow to support current script research. We therefore review the notion of scripts to both promote clarity and better connect it to mainstream situational prevention and criminology more generally. We also seek to broaden the approach by exploring additional cross-disciplinary links. We believe all this will support the progressively more demanding uses to which the procedural analysis of crime may be put in research and practice and—more broadly—challenge how human behaviour in crime is analysed.
The UK government has expressed a desire to increase social mobility, with policies to help achieve this aim focused on reducing inequalities in educational attainment. This paper draws together ...established and new information about the contribution that higher education can make to social mobility using a life-course approach, considering differences by family background in terms of university attendance and achievement, as well as occupation and earnings following graduation. We find substantial socio-economic differences at each stage. Young people from poorer backgrounds are, on average, less likely to go to university than their richer peers. Even among the selected group who do go to university, they are less likely to attend the highest status institutions, less likely to graduate, and less likely to achieve the highest degree classes. These differences in degree outcomes contribute to the lower average earnings of graduates from poorer families, but earnings differentials go well beyond those driven purely by degree attainment or institution attended. The evidence strongly suggests that, even after taking these factors into account, graduates from affluent families are more likely to obtain a professional job and to see higher earnings growth in the labour market. We discuss the implications of these findings for the prospects of higher education as a route to greater social mobility.
Pear production is low due to unfavorable weather conditions, and lack of well-adapted cultivars in the sub-tropical conditions. However, area and production of pear under these conditions is ...increasing because of introduction of cultivars that adapt under such weather conditions. The aim of the present investigation was to find a pear cultivar with sufficient overlapping period of flowering with other cultivars of pear within an orchard, high pollen viability and germination, suitable stigma receptivity and high fruit set. The influence of varied temperature conditions, relative humidity and precipitation availability on flowering and reproductive parameters were also evaluated. The studies were conducted in the orchard of Department of Fruit Science during 2018 and 2019. The flowering period and pollen characteristics of each cultivar of pear were tested under field and in vitro conditions. The pollen size, its viability & germination, stigma receptivity and fruit set were higher in 2019 in Patharnakh cultivar due to favorable climatic conditions as compared to 2018 as well as other cultivars. On the basis of overlap of flowering and rate of success of fruit set, the cultivar Patharnakh can be suggested as the best cultivar among the other investigated cultivars.
Genetic dissection of yield component traits including spike and kernel characteristics is essential for the continuous improvement in wheat yield. Genome-wide association studies (GWAS) have been ...frequently used to identify genetic determinants for spike and kernel-related traits in wheat, though none have been employed in hard winter wheat (HWW) which represents a major class in US wheat acreage. Further, most of these studies relied on assembled diversity panels instead of adapted breeding lines, limiting the transferability of results to practical wheat breeding. Here we assembled a population of advanced/elite breeding lines and well-adapted cultivars and evaluated over four environments for phenotypic analysis of spike and kernel traits. GWAS identified 17 significant multi-environment marker–trait associations (MTAs) for various traits, representing 12 putative quantitative trait loci (QTLs), with five QTLs affecting multiple traits. Four of these QTLs mapped on three chromosomes 1A, 5B, and 7A for spike length, number of spikelets per spike (NSPS), and kernel length are likely novel. Further, a highly significant QTL was detected on chromosome 7AS that has not been previously associated with NSPS and putative candidate genes were identified in this region. The allelic frequencies of important quantitative trait nucleotides (QTNs) were deduced in a larger set of 1,124 accessions which revealed the importance of identified MTAs in the US HWW breeding programs. The results from this study could be directly used by the breeders to select the lines with favorable alleles for making crosses, and reported markers will facilitate marker-assisted selection of stable QTLs for yield components in wheat breeding.
Participation in simulation-based interprofessional education (sim-IPE) may affect students' attitudes towards interprofessional learning (through gaining experience with others) and their ...professional identity (by increasing the 'fit' of group membership). We examined this in two questionnaire studies involving students from four universities in two areas of the UK.
Questionnaire data were collected before and after students took part in a sim-IPE session consisting of three acute scenarios. Questionnaires included the Readiness for Interprofessional Learning Scale (RIPLS) and measures of professional identity derived from the social identity theory literature. In Study 1, only identification with Professional Group (doctor or nurse) was measured, while in Study 2 identification with Student Group (medical or nursing student) and the immediate interprofessional Team worked with in the simulation were also measured. Linear mixed effects regression analysis examined the effect of the simulation session, and differences between medical and nursing students, sites and identity measures.
A total of 194 medical and 266 nursing students completed questionnaires. A five-item subset of RIPLS (RIPLS
) was used in analysis. In both studies RIPLS
increased for all groups following participation in sim-IPE, although this was larger for nursing students in Study 1. Nursing students had consistently higher RIPLS
scores than medical students at one site. Effects of the session on identity varied between sites, and dimensions of identity. Notably, while positive emotions associated with group membership (Ingroup Affect) increased for Student Group, Professional Group and Team, the sense of belonging (Ingroup Ties) and importance (Centrality) of the group increased only for Team. Nursing students had consistently higher identification scores than medical students.
Participation in a sim-IPE session can improve attitudes towards interprofessional learning. It can also enhance professional identity, particularly as related to emotional aspects of group membership, with possible benefits for wellbeing. Changes in identification with the immediate Team suggest positive psychological consequences of ad hoc Team formation in the workplace. Differences between medical and nursing students suggest their differing opportunities to work with other professions during training may change baseline attitudes and identity. However, a single sim-IPE session can still have an additive effect.
The preferential dust source (PDS) scheme enables large‐scale mapping of geomorphology in terms of importance for dust emissions but has not been independently tested other than at local scales. We ...examine the PDS qualitative conceptual model of surface emissivity alongside a quantitative measurement of dust loading from Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue Collection 6 for the Chihuahuan Desert. The predicted ranked importance of each geomorphic type for dust emissions is compared with the actual ranked importance as determined from the satellite‐derived dust loading. For this region, the predicted variability and magnitude of dust emissions from most surface types present coincides with the observed characteristics demonstrating the significance of geomorphological controls on emission. The exception is for areas of low magnitude but persistent emissions such as alluvial surfaces where PDS overpredicts dustiness. As PDS is a good predictor of emissions and incorporates surface dynamics it could improve models of future dust emissions.
Key Points
Geomorphological prediction of dust sources compared with long‐term dust loading from MODIS
Predicted rank importance of geomorphology for dust emissions confirmed by satellite record
Geomorphological dynamics can predict dust emissions and should be included in global dust models
Hyperparathyroid crisis, or "parathyroid storm" is a rare manifestation of primary hyperparathyroidism, characterized by sudden onset of symptomatic, severe hypercalcemia (> 3.5 mmol/L). Hemorrhage ...into a parathyroid adenoma has rarely been reported as an inciting or associated event. We present a case of hemorrhage into a longstanding adenoma presenting with acute onset of profound hypercalcemia and associated complications.
A 60-year-old male presented to hospital with sudden onset of confusion, muscle weakness, and ataxia. Initial labs showed serum calcium 4.79 mmol/L, parathyroid hormone 2043 ng/L; creatinine 364 μmol/L. Review of the patient's medical history indicated a 4-year history of recurrent nephrolithiasis, but no prior documented calcium levels. The hypercalcemia did not respond to 5 days of aggressive medical management with fluid resuscitation, denosumab and calcitonin, and later pamidronate and cinacalcet. He continued to deteriorate, requiring intubation and continuous renal replacement therapy. Imaging demonstrated 4.8 cm cystic right paratracheal mass; Technetium (Tc99m) Sestamibi scintigraphy was non-localizing. Urgent parathyroidectomy was completed, revealing a 5 × 3.3 × 1.8 cm hemorrhagic, atypical hypercellular parathyroid. Unfortunately, the patient died from complications from anticoagulation therapy for treatment of deep vein thrombosis 4 weeks after admission. His renal function had not recovered at the time of his death.
This case gives potential insight into the etiology of hyperparathyroid crisis, and the difficulty in achieving control of hypercalcemia with medical means. Surgical intervention is the definitive management in these cases and should be considered urgently.
Urinary sodium and potassium excretion are associated with blood pressure (BP) and cardiovascular disease (CVD). The exact biological link between these traits is yet to be elucidated. Here, we ...identify 50 loci for sodium and 13 for potassium excretion in a large-scale genome-wide association study (GWAS) on urinary sodium and potassium excretion using data from 446,237 individuals of European descent from the UK Biobank study. We extensively interrogate the results using multiple analyses such as Mendelian randomization, functional assessment, co localization, genetic risk score, and pathway analyses. We identify a shared genetic component between urinary sodium and potassium expression and cardiovascular traits. Ingenuity pathway analysis shows that urinary sodium and potassium excretion loci are over-represented in behavioural response to stimuli. Our study highlights pathways that are shared between urinary sodium and potassium excretion and cardiovascular traits.
Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited ...predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.
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