Movement kinematic and postural control differences when performing a visuomotor skill in real and virtual environments.

Immersive technologies, like virtual and mixed reality, pose a novel challenge for our sensorimotor systems as they deliver simulated sensory inputs that may not match those of the natural environment. These include reduced fields of view, missing or inaccurate haptic information, and distortions of 3D space; differences that may impact the control of motor actions. For instance, reach-to-grasp movements without end-point haptic feedback are characterised by slower and more exaggerated movements. A general uncertainty about sensory input may also induce a more conscious form of movement control. We tested whether a more complex skill like golf putting was also characterized by more consciously controlled movement. In a repeated-measures design, kinematics of the putter swing and postural control were compared between (i) real-world putting, (ii) VR putting, and (iii) VR putting with haptic feedback from a real ball (i.e., mixed reality). Differences in putter swing were observed both between the real world and VR, and between VR conditions with and without haptic information. Further, clear differences in postural control emerged between real and virtual putting, with both VR conditions characterised by larger postural movements, which were more regular and less complex, suggesting a more conscious form of balance control. Conversely, participants actually reported less conscious awareness of their movements in VR. These findings highlight how fundamental movement differences may exist between virtual and natural environments, which may pose challenges for transfer of learning within applications to motor rehabilitation and sport.

Mapping TB incidence across districts in Uganda to inform health program activities.

BACKGROUND: Identifying spatial variation in TB burden can help national TB programs effectively allocate resources to reach and treat all people with TB. However, data limitations pose challenges for subnational TB burden estimation. METHODS: We developed a small-area modeling approach using geo-positioned prevalence survey data, case notifications, and geospatial covariates to simultaneously estimate spatial variation in TB incidence and case notification completeness across districts in Uganda from 2016-2019. TB incidence was estimated using 1) cluster-level data from the national 2014-2015 TB prevalence survey transformed to incidence, and 2) case notifications adjusted for geospatial covariates of health system access. The case notification completeness surface was fit jointly using observed case notifications and estimated incidence. RESULTS: Estimated pulmonary TB incidence among adults varied >10-fold across Ugandan districts in 2019. Case detection increased nationwide from 2016 to 2019, and the number of districts with case detection rates >70% quadrupled. District-level estimates of TB incidence were five times more precise than a model using TB prevalence survey data alone. CONCLUSION: A joint spatial modeling approach provides useful insights for TB program operation, outlining areas where TB incidence estimates are highest and health programs should concentrate their efforts. This approach can be applied in many countries with high TB burden.

CONTEXTE: L'identification des variations spatiales de la charge de morbidité de la TB peut aider les programmes nationaux de lutte contre la TB à allouer efficacement les ressources pour atteindre et traiter toutes les personnes atteintes de TB. Cependant, les limites des données posent des problèmes pour l'estimation de la charge de morbidité infranationale. MÉTHODES: Nous avons développé une approche de modélisation à petite échelle en utilisant des données d'enquête de prévalence géolocalisées, des notifications de cas et des covariables géospatiales pour estimer simultanément la variation spatiale de l'incidence de la TB et l'exhaustivité de la notification des cas dans les districts de l'Ouganda de 2016 à 2019. L'incidence de la TB a été estimée à l'aide 1) des données au niveau des grappes de l'enquête nationale sur la prévalence de la TB de 2014­2015, transformées en incidence, et 2) des notifications de cas ajustées pour tenir compte des covariables géospatiales de l'accès au système de santé. La surface de complétude des notifications de cas a été ajustée conjointement à l'aide des notifications de cas observés et de l'incidence estimée. RÉSULTATS: L'incidence estimée de la TB pulmonaire chez les adultes a été multipliée par >10 dans les districts ougandais en 2019. La détection des cas a augmenté à l'échelle nationale entre 2016 et 2019, et le nombre de districts avec des taux de détection des cas >70% a quadruplé. Les estimations de l'incidence de la TB au niveau des districts étaient cinq fois plus précises qu'un modèle utilisant uniquement les données de l'enquête sur la prévalence de la TB. CONCLUSION: Une approche conjointe de modélisation spatiale fournit des informations utiles pour le fonctionnement des programmes de lutte contre la TB, en décrivant les domaines où les estimations de l'incidence de la TB sont les plus élevées et où les programmes de santé devraient concentrer leurs efforts. Cette approche peut être appliquée dans de nombreux pays où la charge de morbidité de la TB est élevée.

Finding gaps in routine TB surveillance activities in Bangladesh.

BACKGROUND: TB was the leading cause of death from a single infectious pathogen globally between 2014 and 2019. Fine-scale estimates of TB prevalence and case notifications can be combined to guide priority-setting for strengthening routine surveillance activities in high-burden countries. We produce policy-relevant estimates of the TB epidemic at the second administrative unit in Bangladesh.METHODS: We used a Bayesian spatial framework and the cross-sectional National TB Prevalence Survey from 2015-2016 in Bangladesh to estimate prevalence by district. We used case notifications to calculate prevalence-to-notification ratio, a key metric of under-diagnosis and under-reporting.RESULTS: TB prevalence rates were highest in the north-eastern districts and ranged from 160 cases per 100,000 (95% uncertainty interval [UI] 80-310) in Jashore to 840 (UI 690-1020) in Sunamganj. Despite moderate prevalence rates, the Rajshahi and Dhaka Divisions presented the highest prevalence-to-notification ratios due to low case notifications. Resolving subnational disparities in case detection could lead to 26,500 additional TB cases (UI 8,500-79,400) notified every year.CONCLUSION: This study is the first to produce and map subnational estimates of TB prevalence and prevalence-to-notification ratios, which are essential to target prevention and treatment efforts in high-burden settings. Reaching TB cases currently missing from care will be key to ending the TB epidemic.

The discrimination of geoforensic trace material from close proximity locations by organic profiling using HPLC and plant wax marker analysis by GC.

There is a need to develop a wider empirical research base to expand the scope for utilising the organic fraction of soil in forensic geoscience, and to demonstrate the capability of the analytical techniques used in forensic geoscience to discriminate samples at close proximity locations. The determination of wax markers from soil samples by GC analysis has been used extensively in court and is known to be effective in discriminating samples from different land use types. A new HPLC method for the analysis of the organic fraction of forensic sediment samples has also been shown recently to add value in conjunction with existing inorganic techniques for the discrimination of samples derived from close proximity locations. This study compares the ability of these two organic techniques to discriminate samples derived from close proximity locations and finds the GC technique to provide good discrimination at this scale, providing quantification of known compounds, whilst the HPLC technique offered a shorter and simpler sample preparation method and provided very good discrimination between groups of samples of different provenance in most cases. The use of both data sets together gave further improved accuracy rates in some cases, suggesting that a combined organic approach can provide added benefits in certain case scenarios and crime reconstruction contexts.

Unstable variant of NADH methemoglobin reductase in Puerto Ricans with hereditary methemoglobinemia.

The electrophoretic mobility of erythrocyte NADH methemoglobin reductase in five hereditary methemoglobinemia patients from three Puerto Rican kindreds was 118% of normal at pH 8.6. The methemoglobin ferrocyanide reductase activity of the enzyme in erythrocyte hemolysates was 3.2-6.4% of normal. Electrophoresis of hemolysates prepared from the blood of patients from two different families at six pH values between 4.6 and 9.3 did not differentiate between the variant enzymes. Examination of the deficient enzymes extracted from the erythrocytes of one patient from each kindred revealed altered affinity for NADH and dichloroindophenol dye and decreased thermal stability. The quantitative similarity of the abnormal findings, together with the Puerto Rican origin of the kindreds, suggested that the cyanotic patients possessed the same abnormal enzyme and were thus homozygous for the same rare mutant gene. Consanguinity of the kindreds could not be established. The rates of decline of the normal and variant NADH methemoglobin reductase enzymes in vivo were measured in erythrocyte fractions of increasing cell age. The rate of decline of the variant enzyme was increased 20-fold by comparison with the normal enzyme. The methemoglobin percentage in erythrocyte fractions of increasing cell age correlated inversely with the activity of the variant. The variant enzyme averaged 37% of normal mean activity in young cells and 1% in old cells. The normal enzyme, on the other hand, lost only one-sixth of its activity as the cells aged, and the methemoglobin content in old normal cells did not rise. These observations support the hypothesis that the deficient activity and the heterogeneous pattern of methemoglobin accumulation in vivo arise principally from the accelerated inactivation of variant NADH methemoglobin reductase during the life-span of the red blood cell.

Cytokine profiles in women with different subtypes of major depressive disorder.

BACKGROUND: Depression has been associated with activation of the immune system. Some studies have shown increased levels of pro-inflammatory cytokines in patients with major depressive disorder (MDD), but conflicting results also have been described. METHODS: Forty-six unmedicated women with MDD were classified in subgroups (melancholic vs. non-melancholic; acute vs. chronic; severe vs. moderate, and episodic vs. recurrent presentations) and compared with 41 healthy controls. Evaluations of serum IL-1beta, IL-6, IFN-gamma and cortisol were performed on both groups. Patients were evaluated prior and after antidepressant treatment. RESULTS: The sub-classification of depression did not predict differences in cytokine levels. Patients currently depressed had similar levels of cytokines and cortisol as healthy controls. After remission of the symptoms, patients with MDD evolved with enhancement of cytokine levels, but no differences were observed in cortisol levels. LIMITATIONS: In patient treatment, two different classes of antidepressants were applied. The dexamethasone/CRH test was not performed to evaluate the HPA axis. CONCLUSIONS: Out-patient women diagnosed with MDD exhibited normal levels of both cortisol and cytokines before treatment, yet demonstrated an increase in cytokines after antidepressant treatment. In some patients with MDD, the presence of acute stress due to hospitalization may indeed contribute and justify the usual finding of higher levels in both cortisol and cytokines.

Auditory white noise reduces age-related fluctuations in balance.

Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability.

Chondrocyte deformation within mechanically and enzymatically extracted chondrons compressed in agarose.

Within articular cartilage, the chondron microenvironment will influence chondrocyte behaviour and response to loading. Chondrons were extracted from intact cartilage using either mechanical homogenisation (MC) or enzymatic digestion (EC) and cell and matrix morphology in unstrained and compressed agarose constructs was examined. Isolated chondrocytes (IC) were used for comparison. Immunolocalisation of type VI collagen and keratan sulphate revealed differences in the structure of the pericellular microenvironment such that MC most closely resembled chondrons in situ. The unstrained cell diameters of IC and EC were larger than MC at day 1 and increased significantly over a 7 day culture period. In contrast, cell diameters for MC remained constant. Compression of constructs at day 1 resulted in cell deformation for IC and EC but not MC. The two chondron extraction methods yielded chondrons of differing matrix morphology and associated differences in cell size and cellular response to load. The results indicate that the pericellular microenvironment of MC initially possessed a greater mechanical integrity than that of EC. Although these differences may be reduced with time in culture, characterisation of mechanically isolated chondrons suggests that the stiffness of the chondrons in situ may be greater than previous estimates.

Anaphylaxis and immunologic insulin resistance in a diabetic woman with ketoacidosis.

A diabetic woman presented with diabetic ketoacidosis after demonstrating immediate-type hypersensitivity to heterologous insulin. She had had interrupted insulin therapy in the past. Insulin requirements during the course of treatment for the acidosis suggested marked resistance, with 50,000 U of insulin needed in the first 36 h. Anaphylaxis requiring intubation and emergency treatment developed after intravenous purified pork insulin was administered. Elevated titers of insulin-specific IgG (441.6 U/L serum) demonstrated immunologic insulin resistance. Positive intradermal skin tests for beef and pork insulins and detection of insulin-specific IgE by RAST assay revealed concurrent immediate-type allergy. A review of the literature revealed the unique occurrence in this patient of simultaneous ketoacidosis, insulin allergy, anaphylaxis, and immunologic resistance. Interrupted insulin therapy in susceptible individuals remains a potential danger, even with the availability of purified insulin preparations.

The decision to enter a randomized trial of tamoxifen for the prevention of breast cancer in healthy women: an analysis of the tradeoffs.

OBJECTIVE: Interest in breast cancer prevention has led to the Breast Cancer Prevention Trial (BCPT), a controversial randomized trial of tamoxifen for women at risk for breast cancer. The goal of our study was to determine whether the potential benefits of enrolling in the randomized trial of prophylactic tamoxifen outweigh the potential risks. METHODS: We used a decision analytic model based on the available data on tamoxifen treatment benefits in women with breast cancer and extrapolated to its use in healthy women. RESULTS: For a 50-year-old woman with a breast cancer risk twice that of the average woman her age, the BCPT offers an increase in life expectancy of about 9 days, a gain that is modest compared with other health interventions. For women ages 35 to 60 who meet the minimum risk of breast cancer for trial eligibility, the trial increases life expectancy by about 8 or 9 days. Assumptions about the effect of tamoxifen on the incidence of endometrial and liver cancer and on quality of life associated with tamoxifen did not alter our findings. CONCLUSIONS: Advocates and opponents of the BCPT should temper their concerns to reflect the modest absolute benefits and harms associated with the trial. Although women at increased risk for breast cancer should be aware of the likely overall benefit associated with entry into the trial, for most women, entry into the BCPT is unlikely to alter substantially their length of life, in either a beneficial or harmful manner.

The significance of subendothelial von Willebrand factor.

von Willebrand factor (vWf) serves to bridge between receptors on the platelet cytoplasmic membrane and the extracellular matrix. In addition to circulating in plasma, vWf is deposited into the extracellular matrix of the subendothelium where it is associated with type VI collagen microfibrils, but not with the elastin-associated microfibrils which are present in the deepest portion of the subendothelium at the zone of the internal elastic lamina. The reaction of platelets to type VI collagen in flow systems is qualitatively different from the shear rate dependent adhesion and aggregation response which is observed with fibrillar type I collagen, exhibiting a response only at low shear rates. The adhesion response to type VI collagen is dependent upon vWf, GP Ib and the GP IIb-IIIa complex. Platelets exposed to purified fibrillin-containing elastin-associated microfibrils adhere and aggregate at low shear rates; this response appears to involve GP IIb-IIIa but not GP Ib. The data are consistent with the hypothesis that type VI collagen is a physiologically relevant binding site for vWf in subendothelium.

Fibrillin containing elastic microfibrils support platelet adhesion under dynamic shear conditions.

The vascular subendothelium contains macromolecular structures called microfibrils. Type VI collagen is one protein found in microfibrils that supports platelet adhesion and aggregation and we have previously evaluated the roles of platelet receptors and vWf involved in these processes under physiological shear conditions. Here we investigate the ability of fibrillin containing elastic microfibrils to support mural thrombus formation. Our results show that elastic microfibril surfaces support platelet adhesion under low shear conditions at a level similar to collagen VI tetramers. However, the degree of aggregation on the elastic microfibril surface is much higher. Both adhesion and aggregation were shown to be mediated by the GPIIb-IIIa platelet receptor. Elastic microfibrils do not support the formation of mural thrombi under high shear conditions. These results suggest roles for both collagen VI and fibrillin containing elastic microfibrils in modulating the platelet response to blood vessel injury.

Dual-label immunohistochemical study of interleukin-4-and interferon-gamma-expressing cells within the pancreas of the NOD mouse during disease acceleration with cyclophosphamide.

Beta cell destruction has been shown to occur when rodent or human islets are exposed in vitro to inflammatory cytokines, such as interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). Other cytokines such as interleukin-4 (IL-4) or interleukin-10 (IL-10), when given to NOD mice, prevent insulin-dependent diabetes mellitus (IDDM). In this study, we have employed immunofluorescence histochemistry to study the expression of IFN-gamma and IL-4 in the pancreas of female NOD mice at various time-points (days 0, 4, 7, 11 and at onset of diabetes) following disease acceleration with cyclophosphamide (Cy). Dual-label confocal and light microscopy were employed to determine the precise cellular sources of the two cytokines. IL-4 immunolabelling was observed in a few immune cells at days 0, 4, and 7 within the pancreatic islets but in larger numbers at day 11 and at onset of diabetes. The cytokine was co-localized predominantly in CD4 cells, while only a small minority of CD8 cells and macrophages also expressed IL-4. At days 0, 4, 7 and 11, weak to moderate immunolabelling for IL-4 was also observed in beta cells. In contrast, immunolabelling for IFN-gamma within the islets was not observed until day 11 and this labelling persisted at onset of diabetes. It was immunolocalized in macrophages and to a lesser extent in CD4 cells. Only a few CD8 cells were immunopositive for IFN-gamma. At day 11, a proportion of beta cells showed weak immunolabelling for IFN-gamma. During the study period, immunolabelling for IFN-gamma was also observed in a proportion of endothelial cells located in the intra-islet and exocrine regions of Cy and diluent-treated mice. From day 11 onwards, both the cytokines were observed in some of the peri-vascular regions. Our results demonstrate that during Cy-induced diabetes, there is increasing expression of both IL-4 and IFN-gamma in specific immune cells within the inflamed islets in the late prediabetic stage and at onset of diabetes. Further studies are required to correlate our protein immunohistochemical findings with in situ cytokine gene expression and to determine whether there is a clear Th1 cytokine protein bias at clinical onset of diabetes and immediately preceding it.

Association of white cell and red cell antibodies in human sera.

Five hundred and eighteen human sera containing known red cell antibodies were tested for lymphocytotoxic antibodies and 81 sera were found to contain them. Thirty-nine antibodies were fully characterized. The frequencies of anti-I, K, V(w), and Wr(a) were significantly greater in those of the 518 sera which also contained white cell antibodies.Four hundred and ninety-four of the 518 sera containing red cell antibodies contained anti-Rh and anti-Kell. The frequency of white cell antibodies in this group was 15% compared with a frequency of 12% in a series of 923 antenatal samples not containing anti-Rh or anti-Kell. The frequencies of different anti-HL-A specificities were compared in the two groups with or without anti-Rh and anti-Kell antibodies. Anti-HL-A 1, 7, and 8 occurred more frequently in the absence of these red cell antibodies and anti-HL-A 12 occurred more frequently in their presence. No correlation was found between particular red cell and white cell antibodies.

Immunohistochemical demonstration of leptin in pancreatic islets of non-obese diabetic and CD-1 mice: co-localization in glucagon cells and its attenuation at the onset of diabetes.

Leptin is a 16 kD polypeptide hormone produced predominantly by white adipose tissue and exerts profound effects on food intake and energy balance. More recent studies have shown extra sites of leptin production in human and rodent tissues and have ascribed additional roles for the hormone, e.g., in immune and reproductive functions. A role for the hormone has also been implicated in insulin-dependent diabetes mellitus in the non-obese diabetic (NOD) mouse. However, whether leptin originates from islet cells of the mouse is not known. Here dual-label immunohistochemistry was employed to examine leptin expression in islet cells, and its distribution and cellular sources in pancreatic sections of female NOD/Ak and CD-1 mice of various ages. For comparison, leptin immunolabelling was examined in adult pancreatic sections from male NOD/Ak CD-1, Balb/c and FVB/N mice and female severe combined immunodeficient CB. 17 mice. Pancreatic tissues from adult female guinea pig, sheep and cattle and neonatal pigs were also studied. Our results show that in the day 1 NOD and CD-1 mice, leptin immunolabelling was observed in selective glucagon cells within the developing islets while at days 15 and 22, it became more intense and co-incident. This pattern of staining was maintained at days 40, 90, 150 and 250. In the female NOD mouse, leptin was absent in intra-islet immune cells. Its expression was variable in islets from male NOD and CD-1 mice. In spontaneously diabetic female NOD mice and following acceleration of diabetes with cyclophosphamide, despite the persistence of strong immunolabelling for glucagon in the re-distributed alpha cells, leptin expression was either absent, diminished or present in only a proportion of alpha cells. The reduction in leptin labelling was often associated with diabetic islets which had insulitis in association with only a small number of residual beta cells. Leptin expression was absent in guinea pig, ovine, bovine and neonatal porcine islet cells, despite the expression of intensely labelled glucagon cells. The present results demonstrate leptin co-localization in glucagon cells of the mouse islet. Its expression diminishes in the presence of inadequate insulin. Leptin produced within the mouse islet may have bi-directional influences on leptin and insulin regulation and may play local functions in islet development and metabolism.

Shear stress affects the kinetics of Staphylococcus aureus adhesion to collagen.

Staphylococcus aureus is a major human pathogen that has been shown to bind collagen under static conditions. However, many staphylococcal infections are hematogenously acquired and adhesion events may be influenced by shear stress. In this study, we used a dynamic experimental system consisting of a parallel-plate perfusion chamber and phase-contrast video microscope to study the effects of shear stress on the adhesion kinetics of intact S. aureus to collagen surfaces in vitro. The adhesion of S. aureus Phillips to collagen types I, II, and IV was investigated over a physiologically relevant range of wall shear stresses at 37 degrees C. S. aureus PH100, a collagen adhesin-deficient mutant strain, was used as a control strain for the experiments. We found that S. aureus Phillips could adhere to collagens I, II, and IV at wall shear stresses less than 15 dyn/cm(2) and that the kinetics of the adhesion process were wall shear stress-dependent. Similar studies with PH100 demonstrated that these cells are unable to adhere firmly to collagen surfaces. Transient interactions between PH100 and the collagen surfaces were observed at low levels of shear stress suggesting that S. aureus may also interact with collagen by an alternative mechanism that does not lead to firm adhesion.

Perforation by central venous catheters: a new testament to an old test.

Perforation by central venous catheters into the extravascular space is a rare complication of central venous lines that may explain new onset shortness of breath in hospitalized patients. We found that lowering bottles containing infusate and looking for return of venous blood is a highly specific test for this problem. Using Bayes' Theorem we calculated that for prior probabilities of catheter perforation of 0.01 and 0.05, corresponding posterior probabilities ranged from 0.1 to 0.15 and 0.35 to 0.49 respectively. This test should be used in all patients with new shortness of breath who have central venous catheters.

Allergy to insulin.

Allergy to insulin occurs in nearly all insulin-treated patients, is a clinical problem in about 15 per cent of patients, and can be life-threatening in 0.1 to 0.2 per cent of patients. This article summarizes the clinical expression of insulin allergy and reviews some aspects that contribute to our understanding and therapy of this allergy.

Genital flora during pregnancy and colonization of the newborn.

A longitudinal study of the cervical and vaginal microflora of 131 pregnant women showed a similar range of organisms at first visit (up to 16 weeks), at 28 weeks and at 36 weeks of pregnancy. Twenty different groups or genera of microorganisms were recovered, predominantly lactobacilli. There was a fall in the isolation rate of organisms in the mothers 6 to 8 weeks after delivery. Lactobacilli and yeasts including Candida albicans were recovered less frequently whereas the incidence of Escherichia coli and group B streptococci increased.Infants born to these mothers were swabbed within 24 hours of delivery and yielded organisms from the umbilicus, ear and mouth in 24%, 33% and 38% of cases respectively. Alpha haemolytic streptococci and Staphylococcus aureus were the predominant organisms. Sixteen different groups or genera were isolated.The isolation rates in non-pregnant women attending a `well-women' clinic were similar to those in the postnatal mothers; few women of 60 years or more were colonized.

Once more onto the couch: consciousness and preconscious defenses in psychoanalysis.

Use of the couch in the analytic situation has a unique impact on the consciousness of both participants in the process. The hypnagogic state of the supine analysand and its resonance with the empathic reverie of the unseen analyst are explored, with a focus not on the contents of analysts' countertransferential associations, but on the diverse but converging modes in which they represent their patients' verbal productions. A clinical example is presented to illustrate the interplay between the patient's and the analyst's imaginations, an understanding of which does away with the false dichotomy between defense analysis and empathic responsiveness. The importance of a patient's conscious and preconscious defenses in the here-and-now transference (suppression, "marginalization," disavowal, negation) is also noted, as is the relation of these defenses to unconscious secondary repression.