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People with Subjective Cognitive Impairment (SCI) may be at increased risk of dementia. In this study we examined amyloid load in 5 SCI subjects and 14 controls using PIB PET scanning. One SCI subject had significantly increased PIB retention in the cortical areas of interest. Larger, longitudinal studies are indicated.
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.
‘Munchausen's syndrome by proxy’ characteristically describes women alleged to have fabricated or induced illnesses in children under their care, purportedly to attract attention. Where conclusive evidence exists the condition's aetiology remains speculative, where such evidence is lacking diagnosis hinges upon denial of wrong-doing (conduct also compatible with innocence). How might investigators obtain objective evidence of guilt or innocence? Here, we examine the case of a woman convicted of poisoning a child. She served a prison sentence but continues to profess her innocence. Using a modified fMRI protocol (previously published in 2001) we scanned the subject while she affirmed her account of events and that of her accusers. We hypothesized that she would exhibit longer response times in association with greater activation of ventrolateral prefrontal and anterior cingulate cortices when endorsing those statements she believed to be false (i.e., when she ‘lied’). The subject was scanned 4 times at 3 Tesla. Results revealed significantly longer response times and relatively greater activation of ventrolateral prefrontal and anterior cingulate cortices when she endorsed her accusers' version of events. Hence, while we have not ‘proven’ that this subject is innocent, we demonstrate that her behavioural and functional anatomical parameters behave as if she were.
Depression is a major public health problem in European countries, and health systems need to ensure access to effective psychological and pharmacological treatments. Research suggests that improvements in depression care require “complex interventions” that implement change in several areas simultaneously.
We describe an observational study of the implementation of a “stepped care” model to provide care for all adults presenting with a new case of depression in a mixed urban-rural area of Scotland with a population of 76,000 people.
A team of 5.2 clinicians provided care for about 1,000 new cases of depression each year. “Guided Self-Help” was the baseline intervention for all patients, supplemented where necessary with pharmacological treatment and Cognitive Behavioural or Interpersonal Therapy.
Service delivery systems were reformed to provide: specialist treatment in primary care settings using primarily non-medical clinicians, comprehensive electronic clinical records, continuous outcome monitoring and intensive investment in staff training and support.
Clinical outcomes (measured by the Personal Health Questionnaire, Social and Work Adjustment Scale and EQ-5D) showed significant improvement despite relatively brief clinician contact (2.5 hours over 4.6 contacts). Savings of more than 50% were made on the antidepressant drug budget. Service user satisfaction ratings were high.
Population needs for depression care can be met using “stepped care” models such as that described above. A randomised controlled study of this approach would be required to fully test the model.
South Africa (SA) is a developing country with an ageing population. Adequate nutrition and physical activity (PA) protect against the loss of muscle mass and physical function, both of which are important components of sarcopenia. This study aimed to measure the prevalence of sarcopenia in older black SA women and investigate its associations with PA and protein intake.
Materials and Methods
Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic questionnaires, 24 h urine collection (estimate protein intake), venous blood (hs-C-reactive protein (hs-CRP) and ferritin), functional tests (grip strength, 3 m timed-up-and-go (TUG), 10 m walk test) and PA monitoring (activPAL). Dual-energy x-ray absorptiometry whole-body scans assessed fat and fat-free soft tissue mass (FFSTM).
According to the European Working group on Sarcopenia in Older People (EWGSOP)2, 2.5% (n = 3) had confirmed sarcopenia of a low severity based on normal physical function. Of the total cohort, 9% (n = 11) had low grip strength, 22.1% (n = 27) had a low appendicular skeletal muscle index (ASMI), and no women had low TUG (s) or gait speed (m/s). Higher ASMI was associated with lower hs-CRP (p = 0.05; Rho = -0.209) and higher ferritin (Rho = 0.252; p = 0.019), grip strength (kg, Rho = 0.223; p = 0.015), and gait speed (m/s, Rho = 0.180; p = 0.050). Protein intake suggested intake of 41.8g/day/ or 0.51 g/kg of body mass/day. Higher total protein intake (g/24h), was associated with higher FFSTM (kg) and ASMI (p < 0.001). PA outcomes were not correlated with FFSTM or ASMI (p > 0.05), however, there was a strong positive correlation of TUG (s) and gait speed (m/s) with time spent: 1) stepping per day (min) and; 2) at a high cadence (> 100 steps/min) (all p < 0.01). Daily step count was 7137 ± 3233 (mean ± Standard deviation), with 97.9 ± 38.7 min of total time spent stepping and 12.6 ± 16.8 min spent stepping at a high cadence (> 100 steps/min). Of note, 13.9% (n = 17) of women were completing > 10,000 steps/day.
Based on the EWGSOP2 criteria, there is a low prevalence of sarcopenia in older black SA women, explained by the maintenance of strength and physical function that directly related to PA, especially that performed at higher intensities. In contrast, low muscle mass was relatively prevalent (22.1%) and was associated with low dietary protein and not PA. Notably, it may be important to review the cut-points of EWGSOP2 criteria to be specific to the older SA women from disadvantaged communities.
Osteoporosis was not a public health concern in black South African (SA) women, until recently when it was reported that the prevalence of vertebral fractures was 9.1% in black compared to 5.0% in white SA women. Accordingly, this study aimed to measure bone mineral density (BMD) of older black SA women and to investigate its association with risk factors for osteoporosis, including strength, muscle and fat mass, dietary intake and objectively measured physical activity (PA).
Methods and materials
Older black SA women (age, 68 (range; 60–85 years) n = 122) completed sociodemographic and quantitative food frequency questionnaires (QFFQ), fasting venous blood samples (25-hydroxycholecalciferol: Vitamin D-25), 24 h urine collection (estimate protein intake), grip strength and PA monitoring (activPAL). Dual-energy x-ray absorptiometry (DXA) scans of the hip (femoral neck and total) and lumbar spine determined BMD and whole-body scans for fat and fat-free soft tissue mass (FFSTM). WHO classifications were used to determine osteopenia (t-score -2.5 to -1), and osteoporosis (t-score < -2.5).
At the lumbar spine 34.4% of the women (n = 42) had osteopenia and 19.7% (n = 24) had osteoporosis. Osteopenia at the left femoral neck was 32% (n = 40) and osteoporosis was 13.1% (n = 16) of participants. The total left hip BMD indicated osteopenia in 27.9% (n = 34) and osteoporosis in 13.1% (n = 16) of participants. Multinomial regression revealed no differences in age (y) or frequency of falls in the past year between all groups (p = 0.727). Compared to those with normal BMD, participants with osteoporosis at the hip neck and lumbar spine were shorter, weighed less and had a lower body mass index (BMI) (all p < 0.05). When adjusted for height, the osteoporotic group (hip neck and lumbar spine) had lower trunk fat (% whole body), FFSTM (kg) and grip strength (kg), compared to those with normal BMD (p < 0.05). Only protein intake (g; 24 h urine analyses) was lower in women with osteoporosis (all sites) compared to those with normal BMD. Fat, carbohydrate and micronutrient intakes (relative to total daily energy intake), and vitamin D concentrations were not associated with BMD (all sites). Number of daily step count and stepping time (min) were inversely associated with BMI (p < 0.05), but not with BMD (all sites; p > 0.05).
A high prevalence of osteopenia and osteoporosis was evident at the lumbar spine and hip in older black SA women. This study highlights the importance of strength, body composition, and protein intake in maintaining BMD and preventing the development of osteoporosis in older women.
To investigate changes in socio-economic inequalities in growth in height, weight, BMI and grip strength in children born during 1955–1993 in Guatemala, a period of marked socio-economic-political change.
We modelled longitudinal data on height, weight, BMI and hand grip strength using Super-Imposition by Translation and Rotation (SITAR). Internal Z-scores summarising growth size, timing and intensity (peak growth velocity, e.g. cm/year) were created to investigate inequalities by socio-economic position (SEP; measured by school attended). Interactions of SEP with date of birth were investigated to capture secular changes in inequalities.
Urban and peri-urban schools in the region of Guatemala City, Guatemala.
Participants were 40 484 children and adolescents aged 3–19 years of Ladino and Maya ancestry (nobservations 157 067).
The difference in height (SITAR size) between lowest and highest SEP decreased from −2·0 (95 % CI −2·2, −1·9) sd to −1·4 (95 % CI −1·5, −1·3) sd in males, and from −2·0 (95 % CI −2·1, −1·9) sd to −1·2 (95 % CI −1·3, −1·2) sd in females over the study period. Inequalities also reduced for weight, BMI and grip strength, due to greater secular increases in lowest-SEP groups. The puberty period was earlier and shorter in higher-SEP individuals (earlier SITAR timing and higher SITAR intensity). All SEP groups showed increases in BMI intensity over time.
Inequality narrowed between the 1960s and 1990s. The lowest-SEP groups were still >1 sd shorter than the highest. Risks remain for reduced human capital and poorer population health for urban Guatemalans.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
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.
Surface mass balance (SMB) is the net input of mass on a glacier's upper surface, composed of snow deposition, melt and erosion processes, and is a major contributor to the overall mass balance. Pine Island Glacier (PIG) in West Antarctica has been dynamically imbalanced since the early 1990s, indicating that discharge of solid ice into the oceans exceeds snow deposition. However, observations of the SMB pattern on the fast flowing regions are scarce, and are potentially affected by the firn's strain history. Here, we present new observations from radar-derived stratigraphy and a relatively dense network of firn cores, collected along a ~900 km traverse of PIG. Between 1986 and 2014, the SMB along the traverse was 0.505 m w.e. a−1 on average with a gradient of higher snow deposition in the South-West compared with the North-East of the catchment. We show that along ~80% of the traverse the strain history amounts to a misestimation of SMB below the nominal uncertainty, but can exceed it by a factor 5 in places, making it a significant correction to the SMB estimate locally. We find that the strain correction changes the basin-wide SMB by ~0.7 Gt a−1 and thus forms a negligible (1%) correction to the glacier's total SMB.
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.
A national need is to prepare for and respond to accidental or intentional disasters categorized as chemical, biological, radiological, nuclear, or explosive (CBRNE). These incidents require specific subject-matter expertise, yet have commonalities. We identify 7 core elements comprising CBRNE science that require integration for effective preparedness planning and public health and medical response and recovery. These core elements are (1) basic and clinical sciences, (2) modeling and systems management, (3) planning, (4) response and incident management, (5) recovery and resilience, (6) lessons learned, and (7) continuous improvement. A key feature is the ability of relevant subject matter experts to integrate information into response operations. We propose the CBRNE medical operations science support expert as a professional who (1) understands that CBRNE incidents require an integrated systems approach, (2) understands the key functions and contributions of CBRNE science practitioners, (3) helps direct strategic and tactical CBRNE planning and responses through first-hand experience, and (4) provides advice to senior decision-makers managing response activities. Recognition of both CBRNE science as a distinct competency and the establishment of the CBRNE medical operations science support expert informs the public of the enormous progress made, broadcasts opportunities for new talent, and enhances the sophistication and analytic expertise of senior managers planning for and responding to CBRNE incidents.
Patients with congenital diaphragmatic hernias often have concomitant congenital heart disease (CHD), with small left-sided cardiac structures as a frequent finding. The goal of this study is to evaluate which left-sided heart structures are affected in neonates with congenital diaphragmatic hernias.
Retrospective review of neonates between May 2007 and April 2015 with a diagnosis of a congenital diaphragmatic hernia was performed. Clinical and echocardiographic data were extracted from the electronic medical record and indexed to body surface area and compared to normative values. Univariable regression models assessed for associations between different variables and length of stay.
Data of 52 patients showed decreased mean z scores for the LVIDd (–3.16), LVIDs (–3.05), aortic annulus (–1.68), aortic sinuses (–2.11), transverse arch (–3.11), and sinotubular junction (–1.47) with preservation of the aorta at the diaphragm compared to age-matched normative data with similar body surface areas. Regression analysis showed a percent reduction in length of stay per 1 mm size increase for LVIDd (8%), aortic annulus (27%), aortic sinuses (18%), sinotubular junctions (20%), and transverse arches (25%).
Patients with congenital diaphragmatic hernias have significantly smaller left-sided heart structures compared to age-matched normative data. Aortic preservation at the diaphragm provides evidence for a mass effect aetiology with increased right-to-left shunting at the fetal ductus resulting in decreased size. Additionally, length of stay appears to be prolonged with decreasing size of several of these structures. These data provide quantitative evidence of smaller left-sided heart structures in patients with congenital diaphragmatic hernias.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
Domestic dogs display complex roaming behaviours, which need to be captured to more realistically model the spread of rabies. We have previously shown that roaming behaviours of domestic dogs can be categorised as stay-at-home, roamer and explorer in the Northern Peninsular Area (NPA), Queensland, Australia. These roaming behaviours are likely to cause heterogeneous contact rates that influence the speed or pattern of rabies spread in a dog population. The aim of this study was to define contact spatial kernels using the overlap of individual dog utilisation distributions to describe the daily probability of contact between pairs of dogs exhibiting these three a priori roaming behaviours. We further aimed to determine if the kernels lead to different predicted rabies outbreaks (outbreak duration and number of rabid dogs) by incorporating the spatial kernels into a previously developed rabies spread model for the NPA. Spatial kernels created with both dogs in a pair being explorers or one dog explorer and one dog roamer (who roamed away from their residence) produced short but large outbreaks compared with spatial kernels with at least one stay-at-home dog. Outputs from this model incorporating heterogeneous contacts demonstrate how roaming behaviours influence disease spread in domestic dog populations.
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.
This commentary relates Hoerl & McCormack's dual systems perspective to models of cognitive development emphasizing representational redescription and the role of culturally constructed tools, including language, in providing flexible formats for thinking. We describe developmental processes that enable children to construct a mental time line, situate themselves in time, and overcome the primacy of the here and now.