Theoretical analysis predicts that enhanced erosion related to late Cenozoic global cooling can act as a first-order influence on the internal dynamics of mountain building, leading to a reduction in ...orogen width and height. The strongest response is predicted in orogens dominated by highly efficient alpine glacial erosion, producing a characteristic pattern of enhanced erosion on the windward flank of the orogen and maximum elevation controlled by glacier equilibrium line altitude, where long-term glacier mass gain equals mass loss. However, acquiring definitive field evidence of an active tectonic response to global climate cooling has been elusive. Here we present an extensive new low-temperature thermochronologic data set from the Patagonian Andes, a high-latitude active orogen with a well-documented late Cenozoic tectonic, climatic and glacial history. Data from 38° S to 49° S record a marked acceleration in erosion 7 to 5 Myr ago coeval with the onset of major Patagonian glaciation and retreat of deformation from the easternmost thrust front. The highest rates and magnitudes of erosion are restricted to the glacial equilibrium line altitude on the windward western flank of the orogen, as predicted in models of glaciated critical taper orogens where erosion rate is a function of ice sliding velocity. In contrast, towards higher latitudes (49° S to 56° S) a transition to older bedrock cooling ages signifies much reduced late Cenozoic erosion despite dominantly glacial conditions here since the latest Miocene. The increased height of the orogenic divide at these latitudes (well above the equilibrium line altitude) leads us to conclude that the southernmost Patagonian Andes represent the first recognized example of regional glacial protection of an active orogen from erosion, leading to constructive growth in orogen height and width.
ObjectiveCommunication is a key competency for medical education and comprehensive patient care. In rural environments, communication between rural family physicians and urban specialists is an ...essential pathway for clinical decision making. The aim of this study was to explore rural physicians’ perspectives on communication with urban specialists during consultations and referrals.SettingNewfoundland and Labrador, Canada.ParticipantsThis qualitative study involved semistructured, one-on-one interviews with rural family physicians (n=11) with varied career stages, geographical regions, and community sizes.ResultsFour themes specific to communication in rural practice were identified. The themes included: (1) understanding the contexts of rural care; (2) geographical isolation and patient transfer; and (3) respectful discourse; and (4) overcoming communication challenges in referrals and consultations.ConclusionsCommunication between rural family physicians and urban specialists is a critical task in providing care for rural patients. Rural physicians see value in conveying unique aspects of rural clinical practice during communication with urban specialists, including context and the complexities of patient transfers.
During the coronavirus disease 2019 (COVID‐19) pandemic, providers and patients must engage in shared decision making regarding the pros and cons of early versus delayed interventions for localized ...skin cancer. Patients at highest risk of COVID‐19 complications are older; are immunosuppressed; and have diabetes, cancer, or cardiopulmonary disease, with multiple comorbidities associated with worse outcomes. Physicians must weigh the patient's risk of COVID‐19 complications in the event of exposure against the risk of worse oncologic outcomes from delaying cancer therapy. Herein, the authors have summarized current data regarding the risk of COVID‐19 complications and mortality based on age and comorbidities and have reviewed the literature assessing how treatment delays affect oncologic outcomes. They also have provided multidisciplinary recommendations regarding the timing of local therapy for early‐stage skin cancers during this pandemic with input from experts at 11 different institutions. For patients with Merkel cell carcinoma, the authors recommend prioritizing treatment, but a short delay can be considered for patients with favorable T1 disease who are at higher risk of COVID‐19 complications. For patients with melanoma, the authors recommend delaying the treatment of patients with T0 to T1 disease for 3 months if there is no macroscopic residual disease at the time of biopsy. Treatment of tumors ≥T2 can be delayed for 3 months if the biopsy margins are negative. For patients with cutaneous squamous cell carcinoma, those with Brigham and Women's Hospital T1 to T2a disease can have their treatment delayed for 2 to 3 months unless there is rapid growth, symptomatic lesions, or the patient is immunocompromised. The treatment of tumors ≥T2b should be prioritized, but a 1‐month to 2‐month delay is unlikely to worsen disease‐specific mortality. For patients with squamous cell carcinoma in situ and basal cell carcinoma, treatment can be deferred for 3 months unless the individual is highly symptomatic.
During the coronavirus disease 2019 (COVID‐19) pandemic, providers must help patients to make informed decisions regarding skin cancer management and assess the risk of potential COVID‐19–associated morbidity and/or mortality versus primary skin cancer morbidity and/or mortality. In this article, the authors summarize current data regarding the risk of COVID‐19 complications and mortality based on age and comorbidities, and review the literature assessing how treatment delays affect oncologic outcomes. They provide multidisciplinary recommendations regarding the timing of local therapy for patients with early‐stage skin cancers.
Background & Aims Transoral esophagogastric fundoplication (TF) can decrease or eliminate features of gastroesophageal reflux disease (GERD) in some patients whose symptoms persist despite proton ...pump inhibitor (PPI) therapy. We performed a prospective, sham-controlled trial to determine if TF reduced troublesome regurgitation to a greater extent than PPIs in patients with GERD. Methods We screened 696 patients with troublesome regurgitation despite daily PPI use with 3 validated GERD-specific symptom scales, on and off PPIs. Those with at least troublesome regurgitation (based on the Montreal definition) on PPIs underwent barium swallow, esophagogastroduodenoscopy, 48-hour esophageal pH monitoring (off PPIs), and high-resolution esophageal manometry analyses. Patients with GERD and hiatal hernias ≤2 cm were randomly assigned to groups that underwent TF and then received 6 months of placebo (n = 87), or sham surgery and 6 months of once- or twice-daily omeprazole (controls, n = 42). Patients were blinded to therapy during follow-up period and reassessed at 2, 12, and 26 weeks. At 6 months, patients underwent 48-hour esophageal pH monitoring and esophagogastroduodenoscopy. Results By intention-to-treat analysis, TF eliminated troublesome regurgitation in a larger proportion of patients (67%) than PPIs (45%) ( P = .023). A larger proportion of controls had no response at 3 months (36%) than subjects that received TF (11%; P = .004). Control of esophageal pH improved after TF (mean 9.3% before and 6.3% after; P < .001), but not after sham surgery (mean 8.6% before and 8.9% after). Subjects from both groups who completed the protocol had similar reductions in GERD symptom scores. Severe complications were rare (3 subjects receiving TF and 1 receiving the sham surgery). Conclusions TF was an effective treatment for patients with GERD symptoms, particularly in those with persistent regurgitation despite PPI therapy, based on evaluation 6 months after the procedure. Clinicaltrials.gov no: NCT01136980.
Abstract
Background
The suicide rate in Canada decreased by 24% during the past four decades. However, rates vary between provinces and territories, and not all jurisdictions experienced the same ...changes. This study examined suicide rates over time in the province of Newfoundland and Labrador.
Methods
We used cross-sectional surveillance data from the Canadian Vital Statistics Death Database to examine suicide rates in Newfoundland and Labrador from 1981 to 2018. We calculated annual age-standardized suicide mortality rates and used joinpoint regression to estimate the average annual percent change (AAPC) in suicide rates overall and by sex, age group, and means of suicide.
Results
From 1981 to 2018, 1759 deaths by suicide were recorded among people in Newfoundland and Labrador. The age-standardized suicide mortality rate increased more than threefold over the study period, from 4.6 to 15.4 deaths per 100,000. The suicide rate was higher among males than females, and accounted for 83.1% of suicide deaths (
n
= 1462); the male-to-female ratio of suicide deaths was 4.9 to 1. The average annual percent change in suicide rates was higher among females than males (6.3% versus 2.0%). Age-specific suicide rates increased significantly for all age groups, except seniors (aged 65 or older); the largest increase was among youth aged 10 to 24 years old (AAPC 3.5; 95% CI, 1.6 to 5.5). The predominant means of suicide was hanging/strangulation/suffocation, which accounted for 43.8% of all deaths by suicide.
Conclusions
The suicide rate in Newfoundland and Labrador increased steadily between 1981 and 2018, which was in contrast to the national rate decline. The disparity between the provincial and national suicide rates and the variations by sex and age underscore the need for a public health approach to prevention that accounts for geographic and demographic differences in the epidemiology of suicide.
The Pcf11 protein is an essential subunit of the large complex that cleaves and polyadenylates eukaryotic mRNA precursor. It has also been functionally linked to gene-looping, termination of RNA ...Polymerase II (Pol II) transcripts, and mRNA export. We have examined a poorly characterized but conserved domain (amino acids 142-225) of the Saccharomyces cerevisiae Pcf11 and found that while it is not needed for mRNA 3' end processing or termination downstream of the poly(A) sites of protein-coding genes, its presence improves the interaction with Pol II and the use of transcription terminators near gene promoters. Analysis of genome-wide Pol II occupancy in cells with Pcf11 missing this region, as well as Pcf11 mutated in the Pol II CTD Interacting Domain, indicates that systematic changes in mRNA expression are mediated primarily at the level of transcription. Global expression analysis also shows that a general stress response, involving both activation and suppression of specific gene sets known to be regulated in response to a wide variety of stresses, is induced in the two pcf11 mutants, even though cells are grown in optimal conditions. The mutants also cause an unbalanced expression of cell wall-related genes that does not activate the Cell Wall Integrity pathway but is associated with strong caffeine sensitivity. Based on these findings, we propose that Pcf11 can modulate the expression level of specific functional groups of genes in ways that do not involve its well-characterized role in mRNA 3' end processing.
Background
We sought to evaluate the relationship between the preoperative core‐laboratory parathyroid hormone (CL‐PTH) level and the baseline intraoperative PTH (IOPTH) level and assess the impact ...of any differences on clinical decision making in consecutive surgical patients with primary hyperparathyroidism undergoing parathyroidectomy.
Methods
The CL‐PTH and baseline IOPTH levels were compared. The influence of relying on either the CL‐PTH or baseline PTH levels for intraoperative decision making was determined.
Results
Data were available for 316 patients. Baseline IOPTH measurements were usually higher than the CL‐PTH (247 patients; 78.2%) measurements, with a mean difference of 68.2 pg/mL (P < .001). Using the CL‐PTH as a surrogate for the baseline parathyroid hormone (PTH) would have prolonged the operation in 23 patients (7.3%).
Conclusion
Baseline point‐of‐care IOPTH levels were higher than the preoperative CL‐PTH levels in >75% of patients undergoing parathyroidectomy. Using the CL‐PTH in lieu of an IOPTH baseline value would prolong the operation in some patients.
Globally, the suicide rate is two times higher for males than for females. Previous studies in Newfoundland and Labrador did not examine age-specific rates by sex. The objectives of this study were ...to determine suicide rates by sex and age group and to compare the demographic and clinical characteristics of males and females who died by suicide. The age-standardized suicide rate was 4.6 times higher among males than females and was higher for males in most age groups. Rates were highest in the young adult age groups for males (20 to 24 years) and females (35 to 39 years). Males who died by suicide were more likely to be from a rural community and to have died by firearm; females were more likely to die by self-poisoning and to have had a mental illness or substance use history.
When we rely upon gains on some measure to support statements of prescription, we have the obligation to ensure that those measures are valid. Nearly 10 years after an influential National Research ...Council (2001) report on educational assessment identified an explicit model of cognition as one of three necessary components of a valid assessment system, we note that most measures still lack this fundamental cornerstone. In this paper, we draw attention to the construct modeling approach to assessment that strives for coherence and consistency with a model of cognition in which student proficiency varies along a continuum of competence. This approach is illustrated in the context of an assessment of conceptual understanding of certain scientific phenomena given to undergraduates at a large public university (National Research Council 2001).
This article describes the development of an assessment system for adolescent reading comprehension. It presents a research context-a reading intervention implemented in middle and high schools in an ...urban district-which became the impetus for the work. The article outlines the organizational principles of construct modeling that guided the design of the measures and describes the theory and research on adolescent reading that formed the basis of the work. It outlines the technical aspects of the measurement system and the methodology used to analyze internal and external validity. The curriculum-embedded assessment profiled in this study informs teachers about student learning. It also grounds assessment in cognitive and learning theory, thereby linking the assessments to broader content standards and current research and policy. By aligning what is taught with what is assessed, the article adds to a growing body of work that calls for increased integration between reading intervention and assessment teams.
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