The improved prognosis of hypoplastic left heart:A Population-Based Register Study of 343 Cases in England and Wales

Background: Hypoplastic Left Heart Syndrome (HLHS) is a severe congenital heart defect (CHD) characterised by the underdevelopment of the left side of the heart with varying levels of hypoplasia of the left atrium, mitral valve, left ventricle, aortic valve and aortic arch. In the UK, age 12 survival for cases born between 1991 and 1993 was 21%. UK survival estimates corresponding to cases born between 2000 and 2015 were improved at 56%, but survival was examined up to age five only. Contemporary long-term survival estimates play a crucial role in counselling parents following diagnosis. The aim of this study was to report survival estimates up to age 15 for children born with HLHS or hypoplastic left ventricle with additional CHD in England and Wales between 1998 and 2012. Methods: Cases of HLHS notified to four congenital anomaly registers in England and Wales during 1998–2012, matched to Office for National Statistics mortality information, were included. Kaplan-Meier survival estimates to age 15 were reported. Cox regression models were fitted to examine risk factors for mortality. Results: There were 244 cases of HLHS and 99 cases of hypoplastic left ventricle co-occurring with other CHD, with traced survival status. Kaplan-Meier survival estimates for HLHS were 84.4% at age 1 week, 76.2% at 1 month, 63.5% at age 1 year, 58.6% at age 5 years, 54.6% at age 10 years, and 32.6% to age 15 years. The Kaplan-Meier survival estimates for cases of hypoplastic left ventricle co-occurring with additional CHD were 90.9% at age 1 week, 84.9% at 1 month, 73.7% at age 1 year, 67.7% to age 5 years, 59.2% to age 10 years, and 40.3% to age 15 years. Preterm birth (p = 0.007), low birth weight (p = 0.005), and female sex (p = 0.01) were associated with mortality. Conclusions: We have shown that prognosis associated with HLHS in the twenty first century exceeds that of many previous population-based studies, likely due to improvements in intensive care technologies and advances in surgical techniques over the last few decades

Improving Human Health by Increasing Access to Natural Areas: Linking Research to Action at Scale

Report of the 2014 Berkley Workshop Held at the Wingspread Conference Center, Johnson Foundation, Racine, Wisconsin - June 201

Prospective parents’ perspectives on antenatal decision making for the anticipated birth of a periviable infant

Objective: To examine prospective parents’ perceptions of management options and outcomes in the context of threatened periviable delivery, and the values they apply in making antenatal decisions during this period. Study design: Qualitative analysis of 46 antenatal interviews conducted at three tertiary-care hospitals with 54 prospective parents (40 pregnant women, 14 partners) who had received counseling for threatened periviable delivery (40 cases). Results: Participants most often recalled being involved in resuscitation, cerclage, and delivery mode decisions. Over half (63.0%) desired a shared decision-making role. Most (85.2%) recalled hearing about morbidity and mortality, with many reiterating terms like “brain damage”, “disability”, and “handicap”. The potential for disability influenced decision making to variable degrees. In describing what mattered most, participant spoke of giving their child a “fighting chance”; others voiced concerns about “best interest”, a “healthy baby”, “pain and suffering”, and religious faith. Conclusions: Our findings underscore the importance of presenting clear information on disability and eliciting the factors that parents deem most important in making decisions about periviable birth

Genetic and Spatial Structuring of Populus tremuloides in a Mixed-Species Forest of Southwestern Utah, USA

Populus tremuloides Michx. (aspen) is an iconic species of the southwestern United States, where it is known for its extensive clonality. The size of clones and pattern of clonal distribution within and among stands can provide important clues to the species\u27 evolution and ecology, but there are very few studies that have conducted the type of sampling necessary to define these features. We examined the genetic composition and habitat associations of aspen in a mixed-species forest in Cedar Breaks National Monument on the Markagunt Plateau, southwestern Utah. Genetic analysis of 94 stems ≥1 cm diameter at breast height (dbh) selected from a population census of 2742 stems within a contiguous 13.64-ha plot revealed 2 spatially cohesive triploid genets and 2 diploid genets (all differing in 8 to 15 alleles). Aspen abundance within the 13.64 ha varied between 0 and 634 stems/ha across 8 distinct habitat types. Regenerating aspen stems (1 cm ≤ dbh \u3c 5 cm) varied between 0 and 112 stems/ha, with higher levels of regeneration in habitats with greater aspen dominance relative to other tree species. Recent regeneration may have been stimulated by a Dendroctonous rufipennis outbreak in the 1990s, which killed a high proportion of Picea engelmannii. Even though the visual impression is of a single aspen clone, the 4 identified genets suggest a higher-than-expected level of genetic diversity in this mixed-species stand which may confer resilience to increasing climate variability and drought. Furthermore, aspen regeneration in areas of both low and high adult aspen densities show that these mixed stands can support vigorous aspen populations

Simple Guide to Using Generative Artificial Intelligence Writing Tools in Research & Scholarship at UNH

While Artificial Intelligence (AI) technologies have existed for years, the recent arrival of widespread generative AI writing tools such as ChatGPT has provoked varied reactions in the scholarly community worldwide. Undoubtedly easy access to such tools may help to level the scholarly playing field for certain groups, particularly those with limited writing skills or proficiency with English as the primary language for written and oral communication of research and scholarship. There are, however, concerns about these tools, including, but not limited to, the accuracy, consistency, and bias of the information generated, appropriate acknowledgement of source material, and the tools’ lack of ability to reason or to understand meaning when generating output. This simple guide was developed to assist researchers and trainees to understand the fundamental issues with these technologies regarding research integrity

Residual Cajal bodies in coilin knockout mice fail to recruit Sm snRNPs and SMN, the spinal muscular atrophy gene product

Cajal bodies (CBs) are nuclear suborganelles involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs). In addition to snRNPs, they are highly enriched in basal transcription and cell cycle factors, the nucleolar proteins fibrillarin (Fb) and Nopp140 (Nopp), the survival motor neuron (SMN) protein complex, and the CB marker protein, p80 coilin. We report the generation of knockout mice lacking the COOH-terminal 487 amino acids of coilin. Northern and Western blot analyses demonstrate that we have successfully removed the full-length coilin protein from the knockout animals. Some homozygous mutant animals are viable, but their numbers are reduced significantly when crossed to inbred backgrounds. Analysis of tissues and cell lines from mutant animals reveals the presence of extranucleolar foci that contain Fb and Nopp but not other typical nucleolar markers. These so-called “residual” CBs neither condense Sm proteins nor recruit members of the SMN protein complex. Transient expression of wild-type mouse coilin in knockout cells results in formation of CBs and restores these missing epitopes. Our data demonstrate that full-length coilin is essential for proper formation and/or maintenance of CBs and that recruitment of snRNP and SMN complex proteins to these nuclear subdomains requires sequences within the coilin COOH terminus

Changes in undergraduate student alcohol consumption as they progress through university

BACKGROUND: Unhealthy alcohol use amongst university students is a major public health concern. Although previous studies suggest a raised level of consumption amongst the UK student population there is little consistent information available about the pattern of alcohol consumption as they progress through university. The aim of the current research was to describe drinking patterns of UK full-time undergraduate students as they progress through their degree course. METHOD: Data were collected over three years from 5895 undergraduate students who began their studies in either 2000 or 2001. Longitudinal data (i.e. Years 1–3) were available from 225 students. The remaining 5670 students all responded to at least one of the three surveys (Year 1 n = 2843; Year 2 n = 2219; Year 3 n = 1805). Results: Students reported consuming significantly more units of alcohol per week at Year 1 than at Years 2 or 3 of their degree. Male students reported a higher consumption of units of alcohol than their female peers. When alcohol intake was classified using the Royal College of Physicians guidelines [1] there was no difference between male and females students in terms of the percentage exceeding recommended limits. Compared to those who were low level consumers students who reported drinking above low levels at Year 1 had at least 10 times the odds of continuing to consume above low levels at year 3. Students who reported higher levels of drinking were more likely to report that alcohol had a negative impact on their studies, finances and physical health. Consistent with the reduction in units over time students reported lower levels of negative impact during Year 3 when compared to Year 1. CONCLUSION: The current findings suggest that student alcohol consumption declines over their undergraduate studies; however weekly levels of consumption at Year 3 remain high for a substantial number of students. The persistence of high levels of consumption in a large population of students suggests the need for effective preventative and treatment interventions for all year groups

Predicting which children with juvenile idiopathic arthritis will not attain early remission with conventional treatment: Results from the Reacch-out cohort

Objective. To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD). Methods. We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort. The predicted outcome was clinically inactive disease for ≥ 6 months starting within 1 year of JIA diagnosis in patients who did not receive early biologic agents or triple DMARD. Models were developed in 200 random splits of 75% of the cohort and tested on the remaining 25% of subjects, calculating expected and observed frequencies of remission and c-index values. Results. Our best Cox logistic model combining 18 clinical variables a median of 2 days after diagnosis had a c-index of 0.69 (95% CI 0.67-0.71), better than using JIA category alone (0.59, 95% CI 0.56-0.63). Children in the lowest probability decile had a 20% chance of remission and 21% attained remission; children in the highest decile had a 69% chance of remission and 73% attained remission. Compared to 5% of subjects identified by JIA category alone, the model identified 14% of subjects as low chance of remission (probability \u3c 0.25), of whom 77% failed to attain remission. Conclusion. Although the model did not meet our a priori performance threshold (c-index \u3e 0.70), it identified 3 times more subjects with low chance of remission than did JIA category alone, and it may serve as a benchmark for assessing value added by future laboratory/imaging biomarkers

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations