Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will ...experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy.
We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort.
The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%).
Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.
Abstract The Winchcombe meteorite fell on February 28, 2021 and was the first recovered meteorite fall in the UK for 30 years, and the first UK carbonaceous chondrite. The meteorite was widely ...observed by meteor camera networks, doorbell cameras, and eyewitnesses, and 213.5 g (around 35% of the final recovered mass) was collected quickly—within 12 h—of its fall. It, therefore, represents an opportunity to study very pristine extra‐terrestrial material and requires appropriate careful curation. The meteorite fell in a narrow (600 m across) strewn field ~8.5 km long and oriented approximately east–west, with the largest single fragment at the farthest (east) end in the town of Winchcombe, Gloucestershire. Of the total known mass of 602 g, around 525 g is curated at the Natural History Museum, London. A sample analysis plan was devised within a month of the fall to enable scientists in the UK and beyond to quickly access and analyze fresh material. The sample is stored long term in a nitrogen atmosphere glove box. Preliminary macroscopic and electron microscopic examinations show it to be a CM2 chondrite, and despite an early search, no fragile minerals, such as halite, sulfur, etc., were observed.
Backgound: A prospective randomised trial was undertaken to evaluate the role of neoadjuvant chemoendocrine therapy prior to surgery in primary operable breast cancer. Patients and methods: Three ...hundred nine women (median age 56 years, range 27–70) with primary operable breast cancer confirmed on fine needle aspiration (FNA) cytology were recruited to this study. They were treated with a combination of mitozantrone and methotrexate (± mitomycin-C) combined with tamoxifen (2MT). Patients received eight cycles of 2MT (four prior to surgery in the neoadjuvant group) and tamoxifen for five years with appropriate surgery and radiotherapy. The two groups were comparable for age, menopausal status, stage and surgical requirements. Results: The clinical response rates to neoadjuvant therapy were as follows: 22% complete response (CR), 29% minimal residual disease (MRD), 33% partial response (PR), 15% no change (NC) and only two patients had clinical evidence of progressive disease. Surgical requirements were reduced from 31 patients (22%) of the adjuvant group having mastectomy to 14 (10%) in the neoadjuvant group (P < 0.003). At a median follow-up of 48 months (range 10–70 months) there is no statistically significant difference between the two groups in terms of local relapse, metastatic relapse or overall survival. Symptomatic and haematologic acute toxicity was low and similar for adjuvant and neoadjuvant therapy. Conclusion: This randomised trial has shown a significant reduction in the surgical requirements for mastectomy, after treatment with neoadjuvant chemoendocrine therapy, with no deterioration in local or distal relapse.
Summary
Background
Food allergies pose a considerable world‐wide public health burden with incidence as high as one in ten in 12‐month‐old infants. Few food allergy genetic risk variants have yet ...been identified. The Th2 immune gene IL13 is a highly plausible genetic candidate as it is central to the initiation of IgE class switching in B cells.
Objective
Here, we sought to investigate whether genetic polymorphisms at IL13 are associated with the development of challenge‐proven IgE‐mediated food allergy.
Method
We genotyped nine IL13 “tag” single nucleotide polymorphisms (tag SNPs) in 367 challenge‐proven food allergic cases, 199 food‐sensitized tolerant cases and 156 non‐food allergic controls from the HealthNuts study. 12‐month‐old infants were phenotyped using open oral food challenges. SNPs were tested using Cochran‐Mantel‐Haenszel test adjusted for ancestry strata. A replication study was conducted in an independent, co‐located sample of four paediatric cohorts consisting of 203 food allergic cases and 330 non‐food allergic controls. Replication sample phenotypes were defined by clinical history of reactivity, 95% PPV or challenge, and IL13 genotyping was performed.
Results
IL13 rs1295686 was associated with challenge‐proven food allergy in the discovery sample (P=.003; OR=1.75; CI=1.20‐2.53). This association was also detected in the replication sample (P=.03, OR=1.37, CI=1.03‐1.82) and further supported by a meta‐analysis (P=.0006, OR=1.50). However, we cannot rule out an association with food sensitization. Carriage of the rs1295686 variant A allele was also associated with elevated total plasma IgE.
Conclusions and Clinical Relavance
We show for the first time, in two independent cohorts, that IL13 polymorphism rs1295686 (in complete linkage disequilibrium with functional variant rs20541) is associated with challenge‐proven food allergy.
Prepubertal children (6-12 yr) differ from adults in various morphological and physiological factors that may influence thermoregulatory function; however, experimental evidence of meaningful ...child-adult differences in heat strain during exercise-heat stress is sparse, despite numerous studies. Although we appreciate the challenges associated with performing such comparisons, part of that discrepancy may be due to the methods used. Nonetheless, a focused discussion of these methodological considerations and their implications for current understanding remains unavailable. This is an important knowledge gap given the threat to health posed by rising global temperatures and the ongoing focus on improving physical activity levels in children. The aims of this methodological review were, therefore, to (i) review the theoretical basis for child-adult differences in thermoregulatory function, (ii) describe previous comparisons of exercise thermoregulation between prepubertal children and adults, (iii) discuss two methodological issues associated with that research, which, in our view, make it difficult to present empirical evidence related to child-adult differences in thermoregulatory function and associated heat strain, (iv) provide potential solutions to these issues, and (v) propose pertinent areas for further research.
We studied the effects of six levels of dispersed green-tree retention (GTR) harvesting (clearcut (0%), 10%, 20%, 50%, and 75%, and unharvested reference (100%)) on understory plant communities in ...the 8th growing season post-harvest in the mixedwood boreal forest in northwestern Alberta. For the partial harvest treatments (10%, 20%, 50%, 75%) sample plots were located in the partially harvested (retention) strips as well as in the intervening machine corridors used by the harvesting equipment. The understory plant community was significantly influenced by the gradient of retention level. The cover of understory vegetation, especially graminoids, increased with increasing harvesting intensity for the retention strips and overall considering both plots types. Species richness was unaffected by retention level but did decrease as tree density increased. Lower levels of retention lead to increased abundance of early successional, shade-intolerant species. The results suggest a threshold in understory response to GTR harvesting between the 10% and 20% retention treatments. In terms of understory cover and composition, machine corridors within partially harvested forests resembled clearcuts. The results suggest that retaining more than 10% during GTR harvesting could have significant benefits in terms of maintaining understory plant communities more similar to unharvested reference forest.
The present study examined changes in sleep quality following hematopoietic stem cell transplantation (HSCT) and investigated associations with biobehavioral factors. Individuals undergoing HSCT for ...hematologic malignancies (N=228) completed measures of sleep quality and psychological symptoms pre-transplant and 1, 3, 6 and 12 months post transplant. Circulating inflammatory cytokines (IL-6, TNF-α) were also assessed. Sleep quality was poorest at 1 month post transplant, improving and remaining relatively stable after 3 months post transplant. However, approximately half of participants continued to experience significant sleep disturbance at 6 and 12 months post transplant. Mixed-effects linear regression models indicated that depression and anxiety were associated with poorer sleep quality, while psychological well-being was associated with better sleep. Higher circulating levels of IL-6 were also linked with poorer sleep. Subject-level fixed effects models demonstrated that among individual participants, changes in depression, anxiety and psychological well-being were associated with corresponding changes in sleep after covarying for the effects of time since transplant. Sleep disturbance was most severe when depression and anxiety were greatest and psychological well-being was lowest. Findings indicate that sleep disturbance is a persistent problem during the year following HSCT. Patients experiencing depression or anxiety and those with elevated inflammation may be at particular risk for poor sleep.
Conventional T2-weighted (T2W) imaging alone has a poor sensitivity for prostate cancer detection.
To evaluate combined T2W and diffusion-weighted magnetic resonance imaging (DW-MRI) versus T2W MRI ...alone for identifying tumor in patients with prostate cancer.
Fifty-four consecutive patients with prostate cancer (46 stage 1 and 2, 8 stage 3) and sextant biopsies within the previous 3 months were studied. Endorectal MR images were analyzed by two radiologists (1 experienced, 1 trainee) blinded to patient information and histopathology. T2W images were scored first, followed by combined T2W and isotropic apparent diffusion coefficient (ADC) maps calculated from DW-MRI (b = 0, 300, 500, and 800 s/mm(2)). Gland apex, middle, and base for each side were scored negative, indeterminate, or positive for tumor. Imaging data for each sextant were compared with histology. Sensitivity, specificity, and interobserver agreement were calculated.
Sensitivity and specificity for tumor identification significantly improved from 50% and 79.6% (T2W alone, experienced observer) to 73.2% and 80.8% (P<0.001), respectively. For the trainee observer, there was no improvement (44.3% and 72% T2W alone vs. 45.1% and 69.2% T2W plus ADC maps). Interobserver agreement was moderate for T2W imaging alone (kappa 0.51) and fair for T2W plus ADC maps (kappa 0.33).
In an experienced observer, DW-MRI together with T2W imaging can significantly improve tumor identification in prostate cancer.
Background
Despite the existing knowledge about stress, trauma and pregnancy and maternal stress during natural disasters, little is known about what types of trauma pregnant or preconception women ...experience during these disasters. In May 2016, the worst natural disaster in modern Canadian history required the evacuation of nearly 90,000 residents of the Fort McMurray Wood Buffalo (FMWB) area of northern Alberta. Among the thousands of evacuees were an estimated 1850 women who were pregnant or soon to conceive. In August 2017, Hurricane Harvey devastated areas of the United States including Texas, with 30,000 people forced to flee their homes due to the intense flooding.
Objective
To explore immediate and past traumatic experiences of pregnant or preconception women who experienced one of two natural disasters (a wildfire and a hurricane) as captured in their expressive writing. Research questions were: (1) What trauma did pregnant or preconception women experience during the fire and the hurricane? (2) What past traumatic experiences, apart from the disasters, did the women discuss in their expressive writing?
Methods
A qualitative secondary analysis of expressive writing using thematic content analysis was conducted on the expressive writing of 50 pregnant or preconception women who experienced the 2016 Fort McMurray Wood Buffalo Wildfire (n = 25) and the 2017 Houston Hurricane Harvey (n = 25) Narrative data in the form of expressive writing entries from participants of two primary studies were thematically analyzed. One of the expressive writing questions was used in this analysis: “What is the most traumatic, upsetting experience of your entire life, especially that you have never discussed in great detail with others?” NVivo 12 supported thematic content analysis.
Results
For some women, the disasters elicited immense fear and anxiety that surpassed previous traumatic life events. Others, however, disclosed significant past traumas that continue to impact them, including betrayal by a loved one, abuse, maternal health complications, and illness.
Conclusion
We recommend a strengths-based and trauma-informed care approach in both maternal health and post-disaster relief care.
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