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Implementation of genome-scale sequencing in clinical care has significant challenges: the technology is highly dimensional with many kinds of potential results, results interpretation and delivery require expertise and coordination across multiple medical specialties, clinical utility may be uncertain, and there may be broader familial or societal implications beyond the individual participant. Transdisciplinary consortia and collaborative team science are well poised to address these challenges. However, understanding the complex web of organizational, institutional, physical, environmental, technologic, and other political and societal factors that influence the effectiveness of consortia is understudied. We describe our experience working in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, a multi-institutional translational genomics consortium.
A key aspect of the CSER consortium was the juxtaposition of site-specific measures with the need to identify consensus measures related to clinical utility and to create a core set of harmonized measures. During this harmonization process, we sought to minimize participant burden, accommodate project-specific choices, and use validated measures that allow data sharing.
Identifying platforms to ensure swift communication between teams and management of materials and data were essential to our harmonization efforts. Funding agencies can help consortia by clarifying key study design elements across projects during the proposal preparation phase and by providing a framework for data sharing data across participating projects.
In summary, time and resources must be devoted to developing and implementing collaborative practices as preparatory work at the beginning of project timelines to improve the effectiveness of research consortia.
Poor school connectedness (SC), defined as students’ feelings of belonging, safety, and fairness at school, is a risk factor for negative psychosocial outcomes. Few studies have examined the specific relationship between SC and anxiety. This study examined the relation between SC and anxiety within a group of 114 clinically anxious youth (mean age = 10.82; SD = 2.93; 48.2% female; 70.2% White, non-Hispanic); age differences were also examined. Results indicated that SC was significantly negatively associated with age but unrelated to gender, race/ethnicity, socio-economic status, parent education, or presence of a comorbid disorder. Findings generally revealed that low SC was associated with greater total and domain specific anxiety. SC may play a unique role in the maintenance of global and domain specific anxiety symptoms.
Few records in the alpine landscape of western North America document the geomorphic and glaciologic response to climate change during the Pleistocene–Holocene transition. While moraines can provide snapshots of glacier extent, high-resolution records of environmental response to the end of the Last Glacial Maximum, Younger Dryas cooling, and subsequent warming into the stable Holocene are rare. We describe the transition from the late Pleistocene to the Holocene using a ~ 17,000-yr sediment record from Swiftcurrent Lake in eastern Glacier National Park, MT, with a focus on the period from ~ 17 to 11 ka. Total organic and inorganic carbon, grain size, and carbon/nitrogen data provide evidence for glacial retreat from the late Pleistocene into the Holocene, with the exception of a well-constrained advance during the Younger Dryas from 12.75 to 11.5 ka. Increased detrital carbonate concentration in Swiftcurrent Lake sediment reflects enhanced glacial erosion and sediment transport, likely a result of a more proximal ice terminus position and a reduction in the number of alpine lakes acting as sediment sinks in the valley.
We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.
A nationwide initiative was implemented in February 2014 to decrease Clostridium difficile infections (CDI) in Veterans Affairs (VA) long-term care facilities. We report a baseline of national CDI data collected during the 2 years before the Initiative.
Personnel at each of 122 reporting sites entered monthly retrospective CDI case data from February 2012 through January 2014 into a national database using case definitions similar to those used in the National Healthcare Safety Network Multidrug-Resistant Organism/CDI module. The data were evaluated using Poisson regression models to examine infection occurrences over time while accounting for admission prevalence and type of diagnostic test.
During the 24-month analysis period, there were 100,800 admissions, 6,976,121 resident days, and 1,558 CDI cases. The pooled CDI admission prevalence rate (including recurrent cases) was 0.38 per 100 admissions, and the pooled nonduplicate/nonrecurrent community-onset rate was 0.17 per 100 admissions. The pooled long-term care facility–onset rate and the clinically confirmed (ie, diarrhea or evidence of pseudomembranous colitis) long-term care facility–onset rate were 1.98 and 1.78 per 10,000 resident days, respectively. Accounting for diagnostic test type, the long-term care facility–onset rate declined significantly (P=.05), but the clinically confirmed long-term care facility–onset rate did not.
VA long-term care facility CDI rates were comparable to those in recent reports from other long-term care facilities. The significant decline in the long-term care facility-onset rate but not in the clinically confirmed long-term care facility–onset rate may have been due to less testing of asymptomatic patients. Efforts to decrease CDI rates in long-term care facilities are necessary as part of a coordinated approach to decrease healthcare-associated infections.
Infect. Control Hosp. Epidemiol. 2016;37(3):295–300
A trend toward greater body size in dizygotic (DZ) than in monozygotic (MZ) twins has been suggested by some but not all studies, and this difference may also vary by age. We analyzed zygosity differences in mean values and variances of height and body mass index (BMI) among male and female twins from infancy to old age. Data were derived from an international database of 54 twin cohorts participating in the COllaborative project of Development of Anthropometrical measures in Twins (CODATwins), and included 842,951 height and BMI measurements from twins aged 1 to 102 years. The results showed that DZ twins were consistently taller than MZ twins, with differences of up to 2.0 cm in childhood and adolescence and up to 0.9 cm in adulthood. Similarly, a greater mean BMI of up to 0.3 kg/m2 in childhood and adolescence and up to 0.2 kg/m2 in adulthood was observed in DZ twins, although the pattern was less consistent. DZ twins presented up to 1.7% greater height and 1.9% greater BMI than MZ twins; these percentage differences were largest in middle and late childhood and decreased with age in both sexes. The variance of height was similar in MZ and DZ twins at most ages. In contrast, the variance of BMI was significantly higher in DZ than in MZ twins, particularly in childhood. In conclusion, DZ twins were generally taller and had greater BMI than MZ twins, but the differences decreased with age in both sexes.
For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.
The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 1–12)
The incidence of sedation-related complications for procedures is unknown, as mandatory reporting of outcomes is lacking. However, two sources of information are available that can shed light on the risks of sedation encountered in non-operating-room locations. The American Society of Anesthesiologists (ASA) changed the standards for monitoring of ventilation during moderate or deep sedation to require capnography to measure exhaled carbon dioxide unless precluded or invalidated by the nature of the patient, procedure, or equipment. Sedation-induced respiratory depression may cause brain damage and/or death. Brain function monitoring may have a beneficial role for procedural sedation in the future, but requires more investigation. The major controversies in procedural sedation are the choice of sedative agents and the administration of propofol by non-anesthesia providers. Future drugs include potential use of fospropofol and dexmedetomidine for sedation, patient-controlled sedation and analgesia (PCSA), and computer-assisted personalized sedation (CAPS).