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Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
In this article, we review some of the recent developments in instrumentation and methods that have led to the rise of cryo-electron microscopy (cryo-EM) in the life sciences community, and consider how researchers in the materials community might benefit from these advances. Transmission electron microscopy (TEM) is compared with scanning transmission electron microscopy (STEM) for cryogenic imaging in both biological and materials science applications. We discuss the developments in detector technologies that have in part powered the development of cryo-EM and anticipate exciting areas for productive overlap between life science and materials science cryo-EM applications.
New cryogenic characterization techniques for exploring the nanoscale structure and chemistry of intact solid–liquid interfaces have recently been developed. These techniques provide high-resolution information about buried interfaces from large samples or devices that cannot be obtained by other means. These advancements were enabled by the development of instrumentation for cryogenic focused ion beam liftout, which allows intact solid–liquid interfaces to be extracted from large samples and thinned to electron-transparent thicknesses for characterization by cryogenic scanning transmission electron microscopy or atom probe tomography. Future implementation of these techniques will complement current strides in imaging of materials in fluid environments by in situ liquid-phase electron microscopy, providing a more complete understanding of the morphology, surface chemistry, and dynamic processes that occur at solid–liquid interfaces.
To detect modest associations of dietary intake with disease risk, observational studies need to be large and control for moderate measurement errors. The reproducibility of dietary intakes of macronutrients, food groups and dietary patterns (vegetarian and Mediterranean) was assessed in adults in the UK Biobank study on up to five occasions using a web-based 24-h dietary assessment (n 211 050), and using short FFQ recorded at baseline (n 502 655) and after 4 years (n 20 346). When the means of two 24-h assessments were used, the intra-class correlation coefficients (ICC) for macronutrients varied from 0·63 for alcohol to 0·36 for polyunsaturated fat. The ICC for food groups also varied from 0·68 for fruit to 0·18 for fish. The ICC for the FFQ varied from 0·66 for meat and fruit to 0·48 for bread and cereals. The reproducibility was higher for vegetarian status (κ > 0·80) than for the Mediterranean dietary pattern (ICC = 0·45). Overall, the reproducibility of pairs of 24-h dietary assessments and single FFQ used in the UK Biobank were comparable with results of previous prospective studies using conventional methods. Analyses of diet–disease relationships need to correct for both measurement error and within-person variability in dietary intake in order to reliably assess any such associations with disease in the UK Biobank.
To integrate electronic clinical decision support tools into clinical practice and to evaluate the impact on indwelling urinary catheter (IUC) use and catheter-associated urinary tract infections (CAUTIs).
Design, Setting, and Participants
This 4-phase observational study included all inpatients at a multicampus, academic medical center between 2011 and 2015.
Phase 1 comprised best practices training and standardization of electronic documentation. Phase 2 comprised real-time electronic tracking of IUC duration. In phase 3, a triggered alert reminded clinicians of IUC duration. In phase 4, a new IUC order (1) introduced automated order expiration and (2) required consideration of alternatives and selection of an appropriate indication.
Overall, 2,121 CAUTIs, 179,070 new catheters, 643,055 catheter days, and 2,186 reinsertions occurred in 3·85 million hospitalized patient days during the study period. The CAUTI rate per 10,000 patient days decreased incrementally in each phase from 9·06 in phase 1 to 1·65 in phase 4 (relative risk [RR], 0·182; 95% confidence interval [CI], 0·153–0·216; P<·001). New catheters per 1,000 patient days declined from 53·4 in phase 1 to 39·5 in phase 4 (RR, 0·740; 95% CI, 0·730; P<·001), and catheter days per 1,000 patient days decreased from 194·5 in phase 1 to 140·7 in phase 4 (RR, 0·723; 95% CI, 0·719–0·728; P<·001). The reinsertion rate declined from 3·66% in phase 1 to 3·25% in phase 4 (RR, 0·894; 95% CI, 0·834–0·959; P=·0017).
The phased introduction of decision support tools was associated with progressive declines in new catheters, total catheter days, and CAUTIs. Clinical decision support tools offer a viable and scalable intervention to target hospital-wide IUC use and hold promise for other quality improvement initiatives.
The ramus communicans, neural connection between medial and lateral plantar nerves of the horse, was transected to determine the degree to which medial and lateral plantar nerves contribute to the plantar ramus. After 2 months, sections of plantar nerves immediately proximal and distal to the communicating branch were collected and processed for electron microscopy. All examined nerves had undergone Wallerian degeneration and contained regenerating and mature fibers. Layers of the myelin sheath were separated by spaces and vacuoles, indicating demyelination of medial and lateral plantar nerves. Shrunken axons varied in diameter and were surrounded by an irregular axolemma. Shrunken axoplasm of both myelinated and non-myelinated fibers contained ruptured mitochondria and cristae, disintegrating cytoskeleton, and vacuoles of various sizes. The cytoplasm of neurolemmocytes contained various-sized vesicles, ruptured mitochondria within a fragile basal lamina and myelin whorls of multilayered structures indicative of Wallerian degeneration. These ultrastructural changes, found proximal and distal to the ramus in medial and lateral plantar nerves, suggest that axonal flow is bi-directional through the ramus communicans of the pelvic limbs of horses, a previously unreported finding. As well, maturity of nerves proximal and distal to the ramus indicates that all nerve fibers do not pass through the ramus.
It is increasingly essential for medical researchers to be literate in statistics, but the requisite degree of literacy is not the same for every statistical competency in translational research. Statistical competency can range from ‘fundamental’ (necessary for all) to ‘specialized’ (necessary for only some). In this study, we determine the degree to which each competency is fundamental or specialized.
We surveyed members of 4 professional organizations, targeting doctorally trained biostatisticians and epidemiologists who taught statistics to medical research learners in the past 5 years. Respondents rated 24 educational competencies on a 5-point Likert scale anchored by ‘fundamental’ and ‘specialized.’
There were 112 responses. Nineteen of 24 competencies were fundamental. The competencies considered most fundamental were assessing sources of bias and variation (95%), recognizing one’s own limits with regard to statistics (93%), identifying the strengths, and limitations of study designs (93%). The least endorsed items were meta-analysis (34%) and stopping rules (18%).
We have identified the statistical competencies needed by all medical researchers. These competencies should be considered when designing statistical curricula for medical researchers and should inform which topics are taught in graduate programs and evidence-based medicine courses where learners need to read and understand the medical research literature.
Mass-casualty (MASCAL) events are known to occur in the combat setting. There are very limited data at this time from the Joint Theater (Iraq and Afghanistan) wars specific to MASCAL events. The purpose of this report was to provide preliminary data for the development of prehospital planning and guidelines.
Cases were identified using the Department of Defense (DoD; Virginia USA) Trauma Registry (DoDTR) and the Prehospital Trauma Registry (PHTR). These cases were identified as part of a research study evaluating Tactical Combat Casualty Care (TCCC) guidelines. Cases that were designated as or associated with denoted MASCAL events were included.
Fifty subjects were identified during the course of this project. Explosives were the most common cause of injuries. There was a wide range of vital signs. Tourniquet placement and pressure dressings were the most common interventions, followed by analgesia administration. Oral transmucosal fentanyl citrate (OTFC) was the most common parenteral analgesic drug administered. Most were evacuated as “routine.” Follow-up data were available for 36 of the subjects and 97% were discharged alive.
The most common prehospital interventions were tourniquet and pressure dressing hemorrhage control, along with pain medication administration. Larger data sets are needed to guide development of MASCAL in-theater clinical practice guidelines.
SchauerSG, AprilMD, SimonE, MaddryJK, CarterR III, DelorenzoRA. Prehospital Interventions During Mass-Casualty Events in Afghanistan: A Case Analysis. Prehosp Disaster Med. 2017;32(4):465–468.
Gurga Chiya and Tepe Marani are small, adjacent mounds located close to the town of Halabja in the southern part of the Shahrizor Plain, one of the most fertile regions of Iraqi Kurdistan. Survey and excavation at these previously unexplored sites is beginning to produce evidence for human settlement spanning the sixth to the fourth millennia, c. 5600–3300 cal. b.c. In Mesopotamian chronology this corresponds to the Late Neolithic through to Chalcolithic periods; the Halaf, Ubaid, and Uruk phases of conventional culture history. In Iraqi Kurdistan, documentation of these periods—which witnessed many important transformations in prehistoric village life—is currently very thin. Here we offer a preliminary report on the emerging results from the Shahrizor Plain, with a particular focus on the description of material culture (ceramic and lithic assemblages), in order to establish a benchmark for further research. We also provide a detailed report on botanical remains and accompanying radiocarbon dates, which allow us to place this new evidence in a wider comparative framework. A further, brief account is given of Late Bronze Age material culture from the upper layers at Gurga Chiya. We conclude with observations on the significance of the Shahrizor Plain for wider research into the later prehistory of the Middle East, and the importance of preserving and investigating its archaeological record.
The Aravind Eye Care System (Aravind) is a massive network of ophthalmologic hospitals and primary eye care centers in the state of Tamil Nadu in southern India, joined by educational and research institutes, community outreach programs, an eye bank, and a manufacturing arm for lenses. Aravind is famous for its immense contributions to provision of healthcare to the poor. Over the course of its history, Aravind has treated millions of impoverished people in need of eye care. Most remarkably, Aravind has found ways to deliver this care in a financially profitable way.
This history constitutes one of the greatest success stories of providing business solutions to the “bottom of the pyramid,” or BOP (see Chapter 11). The BOP refers to the poorest and largest segment of the population. This is a challenging population segment to serve for several reasons: they have been traditionally underserved, and thus have greater healthcare needs; they have few resources (both capital and human capital); they are a dispersed and heavily rural population; and they enjoy few logistical supports to access care. As a result, the BOP has traditionally not been seen as a favorable customer base. Recently, however, they have begun to attract attention as a viable target for generating revenues and profits. Serving them requires unconventional and innovative strategies.
Aravind's experience in serving this segment has provided both inspiration and valuable lessons for healthcare providers throughout the developing world who wish to reach out to the impoverished masses. This chapter chronicles Aravind's past and present roles in the Indian healthcare space, drawing implications both for Aravind as it looks into the future and for other organizations that wish to provide healthcare to the bottom of the pyramid.
Long-term care (LTC) patients are often sent to emergency departments (EDs) by ambulance. In this novel extended care paramedic (ECP) program, specially trained paramedics manage LTC patients on site. The objective of this pilot study was to describe the dispatch and disposition of LTC patients treated by ECPs and emergency paramedics.
Data were collected from consecutive calls to 15 participating LTC facilities for 3 months. Dispatch determinants, transport rates, and relapse rates were described for LTC patients attended by ECPs or emergency paramedics. ECP involvement in end-of-life care was identified.
Of 238 eligible calls, 140 (59%) were attended by an ECP and 98 (41%) by emergency paramedics. Although the top three determinants were the same in each group, the overall distribution of dispatch determinants and acuity differed. In the ECP cohort, 98 of 140 (70%) were treated and released, 33 of 140 (24%) had “facilitated transfer” arranged by an ECP, and 9 of 140 (6%) were immediately transported to the ED by ambulance. In the emergency paramedic cohort, 77 of 98 (79%) were immediately transported to the ED and 21 of 98 (21%) were not transported. In the ECP group, 6 of 98 (6%) patients not transported triggered a 911 call within 48 hours for a related clinical reason, although none of the patients not transported by emergency paramedics relapsed.
ECP involvement in LTC calls was found to reduce transports to the ED with a low rate of relapse. These pilot data generated hypotheses for future study, including determination of appropriate populations for ECP care and analysis of appropriate and safe nontransport.
This chapter highlights some important aspects of the design and analysis of clinical trials, and sketches a number of relevant statistical concepts. A controlled clinical trial of a medical intervention should have at least one primary hypothesis that drives its design. Well-designed and well-executed trials include an unambiguous protocol approved by the Institutional Review Boards (IRBs) or Ethics Committees of the participating clinics, laboratories, and data centers. The chapter also describes the basic frequentist statistical testing paradigm used by the typical randomized clinical trial with particular reference to ideas necessary in selecting sample size. Most clinical trials study more than one outcome of interest. Many neurological clinical trials compare therapies with respect to time to occurrence of the primary outcome. In the past, few clinical trials were performed in the Bayesian framework, but Bayesian methods have become more widely used recently.