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Outbreaks of cyclosporiasis, a food-borne illness caused by the coccidian parasite Cyclospora cayetanensis have increased in the USA in recent years, with approximately 2300 laboratory-confirmed cases reported in 2018. Genotyping tools are needed to inform epidemiological investigations, yet genotyping Cyclospora has proven challenging due to its sexual reproductive cycle which produces complex infections characterized by high genetic heterogeneity. We used targeted amplicon deep sequencing and a recently described ensemble-based distance statistic that accommodates heterogeneous (mixed) genotypes and specimens with partial genotyping data, to genotype and cluster 648 C. cayetanensis samples submitted to CDC in 2018. The performance of the ensemble was assessed by comparing ensemble-identified genetic clusters to analogous clusters identified independently based on common food exposures. Using these epidemiologic clusters as a gold standard, the ensemble facilitated genetic clustering with 93.8% sensitivity and 99.7% specificity. Hence, we anticipate that this procedure will greatly complement epidemiologic investigations of cyclosporiasis.
Evidence suggests that healthy older adults with subjective memory complaints are at increased risk of dementia. Subjective Cognitive Impairment (SCI) may precede Mild Cognitive Impairment (MCI) in the clinical continuum of Alzheimer's disease (AD). Attentional deficits may be present early in AD, and associated functional changes have been reported in both MCI and AD. In the present study, activation during divided attention in SCI subjects was investigated using functional magnetic resonance imaging (fMRI). Additionally, amyloid uptake was investigated using 11C-PIB with positron emission tomography (PET).
Brain activation in 11 SCI subjects and 10 controls was compared during a divided attention task using fMRI. Additionally, five SCI subjects and 14 cognitively normal healthy controls underwent 11C-PIB PET scanning. Criteria for diagnosis of SCI were:
1. self-reported memory complaints,
2. objectively normal cognition on detailed neurocognitive testing,
3. absence of psychiatric or causative physical illness,
4. normal activities of daily living and
5. absence of MCI or dementia.
There were no differences in performance between SCI and control groups in terms of cognitive or behavioural measures. However, SCIs had increased activation in left medial temporal lobe, and bilateral thalamus, posterior cingulate and caudate. One SCI subject and one control subject had a pattern of 11C-PIB uptake similar to that seen in AD.
The activation changes identified in SCI may relate to compensatory increased activation in the face of early AD pathology. Larger, longitudinal studies are needed to determine the extent and significance of PIB uptake in SCI.
In this paper, we revisit our previous work in which we derive an effective macroscale description suitable to describe the growth of biological tissue within a porous tissue-engineering scaffold. The underlying tissue dynamics is described as a multiphase mixture, thereby naturally accommodating features such as interstitial growth and active cell motion. Via a linearization of the underlying multiphase model (whose nonlinearity poses a significant challenge for such analyses), we obtain, by means of multiple-scale homogenization, a simplified macroscale model that nevertheless retains explicit dependence on both the microscale scaffold structure and the tissue dynamics, via so-called unit-cell problems that provide permeability tensors to parameterize the macroscale description. In our previous work, the cell problems retain macroscale dependence, posing significant challenges for computational implementation of the eventual macroscopic model; here, we obtain a decoupled system whereby the quasi-steady cell problems may be solved separately from the macroscale description. Moreover, we indicate how the formulation is influenced by a set of alternative microscale boundary conditions.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Congenital and acquired heart diseases are highly prevalent in developing countries despite limited specialised care. Namibia established a paediatric cardiac service in 2009 with significant human resource and infrastructural constraints. Therefore, patients are referred for cardiac interventions to South Africa.
To describe the diagnoses, clinical characteristics, interventions, post-operative morbidity and mortality, and follow-up of patients referred for care.
Demographics, diagnoses, interventions, intra- and post-operative morbidity and mortality, as well as longitudinal follow-up data of all patients referred to South Africa, were recorded and analysed.
The total cohort constituted 193 patients of which 179 (93%) had CHD and 7% acquired heart disease. The majority of patients (78.8%) travelled more than 400 km to Windhoek before transfer. There were 28 percutaneous interventions. Palliative and definitive surgery was performed in 27 and 129 patients, respectively. Out of 156 patients, 80 (51.3%) had post-operative complications, of which 15 (9.6%) were a direct complication of surgery. Surgical mortality was 8/156 (5.1%, 95% confidence interval 2.2–9.8), with a 30-day mortality of 3.2%. Prolonged ICU stay was associated with a 5% increased risk of death with hazard ratio 1.05, 95% confidence interval 1.02–1.08, p=0.001. Follow-up was complete in 151 (78%) patients for more than 7 years.
Despite the challenges associated with a cardiac programme for referring patients seeking intervention in a neighbouring country and the adverse characteristics of multiple lesions and complexity associated with late presentation, we report good surgical and interventional outcomes. Our goal remains to develop a comprehensive sustainable cardiac service in Namibia.
Although only a few specific pigmentation types are allowed within the Hucul horse registry, accurate determination of particular coat colors can be uncertain due to the presence of variation in color shades and segregation of multiple dun dilution variants. Herein, we genotyped the previously identified polymorphisms within two coat color loci TBX3 (T-box 3) and ASIP (Agouti Signaling Protein) in 462 Hucul individuals and compared the genotype predicted phenotypes with observed pigmentation types provided in the Polish Horse Breeders Association database. We identified disagreement between the predicted and recorded coat color in 157 horses (34%). The most common error was misclassification of horses with the nd1/nd1 and nd1/nd2 genotypes, what may be related with the occurrence of some ‘intermediate’ dilution phenotypes in such individuals. We have also proven that the frequency of the dominant dun dilution allele (D) (0.30) is higher than previously predicted by available studbooks. The D allele(s) is easily ‘hidden’ in various phenotypic groups including dark bay and black, therefore we hypothesized that the dun dilution effect itself is not as strongly epistatic in the Hucul horse as described in other horse breeds. This may be the result of an additional genetic modifier suppressing D allele phenotypic effect.
Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
The Pueblo population of Chaco Canyon during the Bonito Phase (AD 800–1130) employed agricultural strategies and water-management systems to enhance food cultivation in this unpredictable environment. Scepticism concerning the timing and effectiveness of this system, however, remains common. Using optically stimulated luminescence dating of sediments and LiDAR imaging, the authors located Bonito Phase canal features at the far west end of the canyon. Additional ED-XRF and strontium isotope (87Sr/86Sr) analyses confirm the diversion of waters from multiple sources during Chaco’s occupation. The extent of this water-management system raises new questions about social organisation and the role of ritual in facilitating responses to environmental unpredictability.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
We derive an effective macroscale description for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effective macroscale description, which incorporates dependence on the microscale structure and dynamics. In particular, the resulting description admits both interstitial growth and active cell motion. This model comprises Darcy flow, and differential equations for the volume fraction of cells within the scaffold and the concentration of nutrient, required for growth. These are coupled with Stokes-type cell problems on the microscale, incorporating dependence on active cell motion and pore scale structure. The cell problems provide the permeability tensors with which the macroscale flow is parameterised. A subset of solutions is illustrated by numerical simulations.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
Cardiometabolic diseases exhibit changes in lipid biology, which is important as lipids have critical roles in membrane architecture, signalling, hormone synthesis, homoeostasis and metabolism. However, Developmental Origins of Health and Disease studies of cardiometabolic disease rarely include analysis of lipids. This short review highlights some examples of lipid pathology and then explores the technology available for analysing lipids, focussing on the need to develop imaging modalities for intracellular lipids. Analytical methods for studying interactions between the complex endocrine and intracellular signalling pathways that regulate lipid metabolism have been critical in expanding our understanding of how cardiometabolic diseases develop in association with obesity and dietary factors. Biochemical methods can be used to generate detailed lipid profiles to establish links between lifestyle factors and metabolic signalling pathways and determine how changes in specific lipid subtypes in plasma and homogenized tissue are associated with disease progression. New imaging modalities enable the specific visualization of intracellular lipid traffic and distribution in situ. These techniques provide a dynamic picture of the interactions between lipid storage, mobilization and signalling, which operate during normal cell function and are altered in many important diseases. The development of methods for imaging intracellular lipids can provide a dynamic real-time picture of how lipids are involved in complex signalling and other cell biology pathways; and how they ultimately regulate metabolic function/homoeostasis during early development. Some imaging modalities have the potential to be adapted for in vivo applications, and may enable the direct visualization of progression of pathogenesis of cardiometabolic disease after poor growth in early life.
Relationships between stable isotopes (δD–δ18O), ice facies and glacier structures have hitherto gone untested in the mid-latitude maritime glaciers of the Southern Hemisphere. Here, we present δD–δ18O values as part of a broader study of the structural glaciology of Fox Glacier, New Zealand. We analyzed 94 samples of δD–δ18O from a range of ice facies to investigate whether isotopes have potential for structural glaciological studies of a rapidly deforming glacier. The δD–δ18O measurements were aided by structural mapping and imagery from terminus time-lapse cameras. The current retreat phase was preceded by an advance of 1 km between 1984 and 2009, with the isotopic sampling and analysis undertaken at the end of that advance (2010/11). Stable isotopes from debris-bearing shear planes near the terminus, interpreted as thrust faults, are isotopically enriched compared with the surrounding ice. When plotted on co-isotopic diagrams (δD–δ18O), ice sampled from the shear planes appears to show a subtle, but distinctive isotopic signal compared with the surrounding clean ice on the lower glacier. Hence, stable isotopes (δD–δ18O) have potential within the structural glaciology field, but larger sample numbers than reported here may be required to establish isotopic contrasts between a broad range of ice facies and glacier structures.
When engaged in conversation, both parents and children tend to re-use words that their partner has just said. This study explored whether proportions of maternal and/or child utterances that overlapped in content with what their partner had just said contributed to growth in mean length of utterance (MLU), developmental sentence score, and vocabulary diversity over time. We analyzed the New England longitudinal corpus from the CHILDES database, comprising transcripts of mother–child conversations at 14, 20, and 32 months, using the CHIP command to compute proportions of utterances with overlapping content. Rates of maternal overlap, but not child overlap, at earlier time-points predicted child language outcomes at later time-points, after controlling for earlier child MLU. We suggest that maternal overlap plays a formative role in child language development by providing content that is immediately relevant to what the child has in mind.
To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source.
A 629-bed, tertiary-care, pediatric hospital in Houston, Texas.
Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units.
We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory.
Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2–148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation.
Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer.
The Dark Energy Survey is undertaking an observational programme imaging 1/4 of the southern hemisphere sky with unprecedented photometric accuracy. In the process of observing millions of faint stars and galaxies to constrain the parameters of the dark energy equation of state, the Dark Energy Survey will obtain pre-discovery images of the regions surrounding an estimated 100 gamma-ray bursts over 5 yr. Once gamma-ray bursts are detected by, e.g., the Swift satellite, the DES data will be extremely useful for follow-up observations by the transient astronomy community. We describe a recently-commissioned suite of software that listens continuously for automated notices of gamma-ray burst activity, collates information from archival DES data, and disseminates relevant data products back to the community in near-real-time. Of particular importance are the opportunities that non-public DES data provide for relative photometry of the optical counterparts of gamma-ray bursts, as well as for identifying key characteristics (e.g., photometric redshifts) of potential gamma-ray burst host galaxies. We provide the functional details of the DESAlert software, and its data products, and we show sample results from the application of DESAlert to numerous previously detected gamma-ray bursts, including the possible identification of several heretofore unknown gamma-ray burst hosts.
This study aimed to review available disaster training options for health care providers, and to provide specific recommendations for developing and delivering a disaster-response-training program for non-disaster-trained emergency physicians, residents, and trainees prior to acute deployment.
A comprehensive review of the peer-reviewed and grey literature of the existing training options for health care providers was conducted to provide specific recommendations.
A comprehensive search of the Pubmed, Embase, Web of Science, Scopus, and Cochrane databases was performed to identify publications related to courses for disaster preparedness and response training for health care professionals. This search revealed 7,681 unique titles, of which 53 articles were included in the full review. A total of 384 courses were found through the grey literature search, and many of these were available online for no charge and could be completed in less than six hours. The majority of courses focused on management and disaster planning; few focused on clinical care and acute response.
There is need for a course that is targeted toward emergency physicians and trainees without formal disaster training. This course should be available online and should utilize a mix of educational modalities, including lectures, scenarios, and virtual simulations. An ideal course should focus on disaster preparedness, and the clinical and non-clinical aspects of response, with a focus on an all-hazards approach, including both terrorism-related and environmental disasters.
HansotiB, KelloggDS, AberleSJ, BroccoliMC, FedenJ, FrenchA, LittleCM, MooreB, SabatoJJr., SheetsT, WeinbergR, ElmesP, KangC. Preparing Emergency Physicians for Acute Disaster Response: A Review of Current Training Opportunities in the US. Prehosp Disaster Med. 2016;31(6):643–647.