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The preparation of semiconductor materials by epitaxial deposition has rapidly gained prominence in recent years. GaAs(1-x)Px alloys of variable composition, deposited on GaAs substrates, have been prepared in an open-tube reactor using H2, AsCl3, and PCl3 with GaAs source material, The deposits ranged in composition from GaAs to GaAs0.5P0.5 and were 10-30 microns thick.
X-ray diffraction topography was employed to evaluate the structural perfection of the monocrystalline GaAs substrates and the perfection of the deposited Ga(As, P) films. A scanning-reflection technique was developed to study the concentration, type, and spatial distribution of imperfections over large areas (∼8 cm2) to depths of 25 microns. Some areas of investigation included (1) the poly cry stallinity of some deposits, (2) the effect of substrate perfection on the film quality, (3) the depth of mechanically induced damage, and (4) the structural perfection of magnesium-diffused GaAs and Ga(As, P).
Measles is a notifiable disease, but not everyone infected seeks care, nor is every consultation reported. We estimated the completeness of reporting during a measles outbreak in The Netherlands in 2013–2014. Children below 15 years of age in a low vaccination coverage community (n = 3422) received a questionnaire to identify measles cases. Cases found in the survey were matched with the register of notifiable diseases to estimate the completeness of reporting. Second, completeness of reporting was assessed by comparing the number of susceptible individuals prior to the outbreak with the number of reported cases in the surveyed community and on a national level.
We found 307 (15%) self-identified measles cases among 2077 returned questionnaires (61%), of which 27 could be matched to a case reported to the national register; completeness of reporting was 8.8%. Based on the number of susceptible individuals and number of reported cases in the surveyed community and on national level, the completeness of reporting was estimated to be 9.1% and 8.6%, respectively. Estimating the completeness of reporting gave almost identical estimates, which lends support to the credibility and validity of both approaches. The size of the 2013–2014 outbreak approximated 31 400 measles infections.
In this chapter, we argue that the timing of societal events in an individual’s life plays a major role in shaping that life through interacting developmental processes at multiple levels. We focus on classic research by Elder showing how two such events in historical proximity dramatically altered the lives of California children who were born at opposite ends of the 1920s, 1920–21 and 1928–29, the Great Depression of the 1930s followed by World War II (1941–45) and the Korean War (1950–53). We employ insights from both Elder’s cohort historical life course approach and developmental science including recent work on developmental neuroscience to understand the life-long impact of exposure to events that occur at different times in life, and the mechanisms through which these exposures may influence development, as well as experiences that may provide turning points in development.
Introduction: Point of care ultrasonography (PoCUS) is an established tool in the initial management of hypotensive patients in the emergency department (ED). It has been shown rule out certain shock etiologies, and improve diagnostic certainty, however evidence on benefit in the management of hypotensive patients is limited. We report the findings from our international multicenter RCT assessing the impact of a PoCUS protocol on diagnostic accuracy, as well as other key outcomes including mortality, which are reported elsewhere. Methods: Recruitment occurred at 4 North American and 3 Southern African sites. Screening at triage identified patients (SBP<100 mmHg or shock index >1) who were randomized to either PoCUS or control groups. Scans were performed by PoCUS-trained physicians. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. Final chart review was blinded to initial impressions and PoCUS findings. Categorical data was analyzed using Fishers two-tailed test. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. The perceived shock category changed more frequently in the PoCUS group 20/127 (15.7%) vs. control 7/125 (5.6%); RR 2.81 (95% CI 1.23 to 6.42; p=0.0134). There was no significant difference in change of diagnostic impression between groups PoCUS 39/123 (31.7%) vs control 34/124 (27.4%); RR 1.16 (95% CI 0.786 to 1.70; p=0.4879). There was no significant difference in the rate of correct category of shock between PoCUS (118/127; 93%) and control (113/122; 93%); RR 1.00 (95% CI 0.936 to 1.08; p=1.00), or for correct diagnosis; PoCUS 90/127 (70%) vs control 86/122 (70%); RR 0.987 (95% CI 0.671 to 1.45; p=1.00). Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We found that the use of PoCUS did change physicians’ perceived shock category. PoCUS did not improve diagnostic accuracy for category of shock or diagnosis.
Introduction: Point of care ultrasound (PoCUS) is an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). While PoCUS protocols have been shown to improve early diagnostic accuracy, there is little published evidence for any mortality benefit. We report the findings from our international multicenter randomized controlled trial, assessing the impact of a PoCUS protocol on survival and key clinical outcomes. Methods: Recruitment occurred at 7 centres in North America (4) and South Africa (3). Scans were performed by PoCUS-trained physicians. Screening at triage identified patients (SBP<100 or shock index>1), randomized to PoCUS or control (standard care and no PoCUS) groups. Demographics, clinical details and study findings were collected prospectively. Initial and secondary diagnoses were recorded at 0 and 60 minutes, with ultrasound performed in the PoCUS group prior to secondary assessment. The primary outcome measure was 30-day/discharge mortality. Secondary outcome measures included diagnostic accuracy, changes in vital signs, acid-base status, and length of stay. Categorical data was analyzed using Fishers test, and continuous data by Student T test and multi-level log-regression testing. (GraphPad/SPSS) Final chart review was blinded to initial impressions and PoCUS findings. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no difference between groups for the primary outcome of mortality; PoCUS 32/129 (24.8%; 95% CI 14.3-35.3%) vs. Control 32/129 (24.8%; 95% CI 14.3-35.3%); RR 1.00 (95% CI 0.869 to 1.15; p=1.00). There were no differences in the secondary outcomes; ICU and total length of stay. Our sample size has a power of 0.80 (α:0.05) for a moderate effect size. Other secondary outcomes are reported separately. Conclusion: This is the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients. We did not find any mortality or length of stay benefits with the use of a PoCUS protocol, though a larger study is required to confirm these findings. While PoCUS may have diagnostic benefits, these may not translate into a survival benefit effect.
Introduction: Point of care ultrasound (PoCUS) has become an established tool in the initial management of patients with undifferentiated hypotension in the emergency department (ED). Current established protocols (e.g. RUSH and ACES) were developed by expert user opinion, rather than objective, prospective data. Recently the SHoC Protocol was published, recommending 3 core scans; cardiac, lung, and IVC; plus other scans when indicated clinically. We report the abnormal ultrasound findings from our international multicenter randomized controlled trial, to assess if the recommended 3 core SHoC protocol scans were chosen appropriately for this population. Methods: Recruitment occurred at seven centres in North America (4) and South Africa (3). Screening at triage identified patients (SBP<100 or shock index>1) who were randomized to PoCUS or control (standard care with no PoCUS) groups. All scans were performed by PoCUS-trained physicians within one hour of arrival in the ED. Demographics, clinical details and study findings were collected prospectively. A threshold incidence for positive findings of 10% was established as significant for the purposes of assessing the appropriateness of the core recommendations. Results: 138 patients had a PoCUS screen completed. All patients had cardiac, lung, IVC, aorta, abdominal, and pelvic scans. Reported abnormal findings included hyperdynamic LV function (59; 43%); small collapsing IVC (46; 33%); pericardial effusion (24; 17%); pleural fluid (19; 14%); hypodynamic LV function (15; 11%); large poorly collapsing IVC (13; 9%); peritoneal fluid (13; 9%); and aortic aneurysm (5; 4%). Conclusion: The 3 core SHoC Protocol recommendations included appropriate scans to detect all pathologies recorded at a rate of greater than 10 percent. The 3 most frequent findings were cardiac and IVC abnormalities, followed by lung. It is noted that peritoneal fluid was seen at a rate of 9%. Aortic aneurysms were rare. This data from the first RCT to compare PoCUS to standard care for undifferentiated hypotensive ED patients, supports the use of the prioritized SHoC protocol, though a larger study is required to confirm these findings.
Introduction: Point of Care Ultrasound (PoCUS) protocols are commonly used to guide resuscitation for emergency department (ED) patients with undifferentiated non-traumatic hypotension. While PoCUS has been shown to improve early diagnosis, there is a minimal evidence for any outcome benefit. We completed an international multicenter randomized controlled trial (RCT) to assess the impact of a PoCUS protocol on key resuscitation markers in this group. We report diagnostic impact and mortality elsewhere. Methods: The SHoC-ED1 study compared the addition of PoCUS to standard care within the first hour in the treatment of adult patients presenting with undifferentiated hypotension (SBP<100 mmHg or a Shock Index >1.0) with a control group that did not receive PoCUS. Scans were performed by PoCUS-trained physicians. 4 North American, and 3 South African sites participated in the study. Resuscitation outcomes analyzed included volume of fluid administered in the ED, changes in shock index (SI), modified early warning score (MEWS), venous acid-base balance, and lactate, at one and four hours. Comparisons utilized a T-test as well as stratified binomial log-regression to assess for any significant improvement in resuscitation amount the outcomes. Our sample size was powered at 0.80 (α:0.05) for a moderate effect size. Results: 258 patients were enrolled with follow-up fully completed. Baseline comparisons confirmed effective randomization. There was no significant difference in mean total volume of fluid received between the control (1658 ml; 95%CI 1365-1950) and PoCUS groups (1609 ml; 1385-1832; p=0.79). Significant improvements were seen in SI, MEWS, lactate and bicarbonate with resuscitation in both the PoCUS and control groups, however there was no difference between groups. Conclusion: SHOC-ED1 is the first RCT to compare PoCUS to standard of care in hypotensive ED patients. No significant difference in fluid used, or markers of resuscitation was found when comparing the use of a PoCUS protocol to that of standard of care in the resuscitation of patients with undifferentiated hypotension.
Early in the history of schistosomiasis research, children under 5 years of age were known to be infected. Although this problem was recognized over 100 years ago, insufficient action has been taken to address this issue. Under current policy, such infected children only receive their first antiparasitic treatment (praziquantel – PZQ) upon entry into primary school as current mass drug administration programmes typically target school-aged children. For many infected children, they will wait up to 6 years before receiving their first medication and significant schistosomiasis-related morbidity may have already established. This inequity would not be accepted for other diseases. To unveil some of the reasons behind this neglect, it is paramount to understand the intricate historical relationship between schistosomiasis and British Imperial medicine, to underline its lasting influence on today's public health priorities. This review presents a perspective on the historical neglect of paediatric schistosomiasis, focusing on important gaps that persist from the early days after discovery of this parasite. Looking to end this inequity, we address several issues that need to be overcome to move forward towards the lasting success of schistosomiasis control and elimination efforts.
This report of Commission 35, as in past reports, consists of some details of only a few selected topics. This is necessary because a survey of the entire field of stellar formation, structure, stability, evolution, pulsation, and explosions for the three year period from mid-1981 to mid-1984 would be excessively long. Our topics here, in order from the most massive stellar classes to the least are: Massive Stars (R.M. Humphreys), Rotation in Late Type Stars (W. Benz), Helioseismology (J. Christensen-Dalsgaard), Planetary Nebula Central Stars (E.M. Sion), Pulsations in Hot Degenerate Dwarf Stars (A.N. Cox and S.D. Kawaler), and White Dwarfs (V. Weidemann). There is some overlap in the reviewing of these last three reports because the topics are very closely related. Concentration in this dying stage of stellar evolution seems appropriate because of the great current interest in these matters.
The public health threat posed by zoonotic Plasmodium knowlesi appears to be growing: it is increasingly reported across South East Asia, and is the leading cause of malaria in Malaysian Borneo. Plasmodium knowlesi threatens progress towards malaria elimination as aspects of its transmission, such as spillover from wildlife reservoirs and reliance on outdoor-biting vectors, may limit the effectiveness of conventional methods of malaria control. The development of new quantitative approaches that address the ecological complexity of P. knowlesi, particularly through a focus on its primary reservoir hosts, will be required to control it. Here, we review what is known about P. knowlesi transmission, identify key knowledge gaps in the context of current approaches to transmission modelling, and discuss the integration of these approaches with clinical parasitology and geostatistical analysis. We highlight the need to incorporate the influences of fine-scale spatial variation, rapid changes to the landscape, and reservoir population and transmission dynamics. The proposed integrated approach would address the unique challenges posed by malaria as a zoonosis, aid the identification of transmission hotspots, provide insight into the mechanistic links between incidence and land use change and support the design of appropriate interventions.
The model diatom Thalassiosira pseudonana is believed to be a single species with a global distribution, but it has not been confirmed previously whether isolates from different environmental and geographic origins are genotypically and phenotypically identical. In the present study, a polyphasic approach was employed to characterize nine clonal isolates, plus an additional replicate of one of the isolates, of the diatom T. pseudonana from culture collections to investigate whether there was any cryptic speciation in the publicly available strains of this species. Morphological analysis using scanning electron microscopy concluded that the strains were indistinguishable. Furthermore, conventional DNA barcoding genes (SSU rDNA, ITS1 and ITS2 rDNA and rbcL), revealed no nucleotide variation among the strains tested. On employing a whole genome fingerprinting technique, Amplified Fragment Length Polymorphism (AFLP), three clusters were revealed, although the level of variation between the clusters was surprisingly low. These findings indicate a low level of diversity among these cultured T. pseudonana strains, despite their wide spatial and temporal distribution and the salinity range of their original habitats. Based on the limited number of available strains, this suggests that T. pseudonana is a highly conserved diatom that nevertheless has an ability to tolerate wide ranges of salinity and populate varied geographic locations.
Q fever patients are often reported to experience a long-term impaired health status, including fatigue, which can persist for many years. During the large Q fever epidemic in The Netherlands, many patients with a laboratory-confirmed Coxiella burnetii infection were not notified as acute Q fever because they did not fulfil the clinical criteria of the acute Q fever case definition (fever, pneumonia and/or hepatitis). Our study assessed and compared the long-term health status of notified and non-notified Q fever patients at 4 years after onset of illness, using the Nijmegen Clinical Screening Instrument (NCSI). The study included 448 notified and 193 non-notified Q fever patients. The most severely affected subdomain in both patient groups was ‘Fatigue’ (50·5% of the notified and 54·6% of the non-notified patients had severe fatigue). Long-term health status did not differ significantly between the notified and non-notified patient groups, and patients scored worse on all subdomains compared to a healthy reference group. Our findings suggest that the magnitude of the 2007–2009 Q fever outbreak in The Netherlands was underestimated when only notified patients according to the European Union case definition are considered.
Understanding the spatial distribution of disease is critical for effective disease control. Where formal address networks do not exist, tracking spatial patterns of clinical disease is difficult. Geolocation strategies were tested at rural health facilities in western Kenya. Methods included geocoding residence by head of compound, participatory mapping and recording the self-reported nearest landmark. Geocoding was able to locate 72·9% [95% confidence interval (CI) 67·7–77·6] of individuals to within 250 m of the true compound location. The participatory mapping exercise was able to correctly locate 82·0% of compounds (95% CI 78·9–84·8) to a 2 × 2·5 km area with a 500 m buffer. The self-reported nearest landmark was able to locate 78·1% (95% CI 73·8–82·1) of compounds to the correct catchment area. These strategies tested provide options for quickly obtaining spatial information on individuals presenting at health facilities.
It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.
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.