Severe fetal acidemia during labour can result in life-lasting neurological deficits, but the timely detection of this condition is often not possible. This is because the positive predictive value ...(PPV) of fetal heart rate (FHR) monitoring, the mainstay of fetal health surveillance during labour, to detect concerning fetal acidemia is around 50%. In fetal sheep model of human labour, we reported that severe fetal acidemia (pH<7.00) during repetitive umbilical cord occlusions (UCOs) is preceded ∼60 minutes by the synchronization of electroencephalogram (EEG) and FHR. However, EEG and FHR are cyclic and noisy, and although the synchronization might be visually evident, it is challenging to detect automatically, a necessary condition for bedside utility. Here we present and validate a novel non-parametric statistical method to detect fetal acidemia during labour by using EEG and FHR. The underlying algorithm handles non-stationary and noisy data by recording number of abnormal episodes in both EEG and FHR. A logistic regression is then deployed to test whether these episodes are significantly related to each other. We then apply the method in a prospective study of human labour using fetal sheep model (n = 20). Our results render a PPV of 68% for detecting impending severe fetal acidemia ∼60 min prior to pH drop to less than 7.00 with 100% negative predictive value. We conclude that this method has a great potential to improve PPV for detection of fetal acidemia when it is implemented at the bedside. We outline directions for further refinement of the algorithm that will be achieved by analyzing larger data sets acquired in prospective human pilot studies.
Abstract Objective To examine social support at initiation of treatment of psychosis and after one year of treatment as predictors of functioning at five year follow-up. Methods Early social support ...was assessed for 132 patients. Follow-up assessments included number of weeks of full-time occupation, number of weeks on a disability pension and global assessment of functioning. Results One year ratings of social support better predicted occupational activity at follow-up than initial social support. Social support predicted functional outcomes independently of other early characteristics. Conclusions Findings support the importance of interventions to improve the level of support of individuals with psychotic disorders.
Purpose: The relationship between anxiety and stuttering has been widely studied. However, a review conducted more than 10 years ago (Menzies, Onslow, & Packman, 1999) identified 5 methodological ...issues thought to preclude consistent research findings regarding the nature of this relationship. The purpose of the present review was to determine whether methodological improvements have occurred since the Menzies et al. (1999) review. Method: Literature published since the Menzies et al. review was evaluated with regard to the 5 methodological issues identified in that review: (a) the construct of anxiety, (b) trait anxiety measures, (c) participant numbers, (d) treatment status of participants, and (e) speaking tasks. Results: Despite some remaining ambiguous findings, research published since the Menzies et al. review has provided far stronger evidence of a relationship between stuttering and anxiety, and has focused more on social anxiety, expectancies of social harm, and fear of negative evaluation. Conclusion: The aims of future research should be to improve research design, increase statistical power, employ multidimensional measures of anxiety, and further develop anxiolytic treatment options for people who stutter.
Schistosoma japonicum is stubbornly persistent in China and the Philippines. Fast and accurate diagnostic tools are required to monitor effective control measures against schistosomiasis japonica. ...Promising antigen candidates for the serological diagnosis of schistosomiasis japonica have generally been identified from the Chinese strain of S. japonicum. However, the Chinese (SjC) and Philippine (SjP) strains of S. japonicum express a number of clear phenotypic differences, including aspects of host immune responses. This feature thereby emphasized the requirement to determine whether antigens identified as having diagnostic value for SjC infection are also suitable for the diagnosis of SjP infection. In the current study, 10 antigens were selected for comparison of diagnostic performance of the SjP infection using ELISA. On testing of sera from 180 subjects in the Philippines, SjSAP4 exhibited the best diagnostic performance with 94.03% sensitivity and 98.33% specificity using an optimized serum dilution. In another large scale testing with 412 serum samples, a combination (SjSAP4+Sj23-LHD (large hydrophilic domain)) provided the best diagnostic outcome with 87.04% sensitivity and 96.67% specificity. This combination could be used in future for serological diagnosis of schistosomiasis in the Philippines, thereby representing an important component for monitoring integrated control measures.
•Sj23-LHD was the most promising antigen candidate for early diagnosis of schistosomiasis japonica in a murine model.•SjSAP4+Sj23-LHD had the highest diagnostic value when probed with sera from a human cohort with low infection intensity.•We have developed a novel diagnostic tool that can aid in the integrated control of schistosomiasis in the Philippines.
Schistosomiasis japonica remains a major public health concern in China and the Philippines. Development of accurate and affordable diagnostic tools is a necessity for the control and elimination of schistosomiasis. The differences in the mammalian host immunological responses to Chinese (SjC) and Philippine (SjP) strains of S. japonicum necessitated validation of proven SjC serological markers for application in the diagnosis of SjP infections. Ten antigens were selected for comparison, in ELISA, for their potential of the diagnosis of SjP infection. The results provide the basis for developing an affordable and easy-to-operate tool for the diagnosis of schistosomiasis in the Philippines.
Although medical school programs oriented toward postgraduate specialty training have the potential to reduce the duration and cost of medical school for US medical students, success depends on the ...ability of students to predict their postgraduate specialties. It is clear that first-year choices are poorly predictive, but it is not known when predictions become sufficiently reliable to support specialty-oriented learning programs. We therefore examined the predictive value of specialty preferences expressed at the ends of the first, second and third years of medical school and asked whether concurrent expressions of confidence in choices improved predictive ability. We also investigated the possibility that discrepancies between predicted and actual postgraduate specialty training were related to scores on an examination of knowledge in basic biomedical sciences required for US medical school graduation (the United States Medical Licensing Examination (USLME) Step 1 examination).
We calculated positive and negative predictive values (PPV and NPV, respectively) for specialty choices and the sensitivity and specificity of asking for choices for 634 University of Colorado School of Medicine students who trained in 23 accredited residencies from 2011 through 2015. We examined the effect of confidence in first choices in 609 students, and in 334 students, sought an association between USMLE Step 1 scores and switching from postgraduate training specialties predicted at the end of year 2.
The PPV of first choices improved from years 1 through 3. NPV was high throughout. PPVs of year 3 first choices ranged from 79% in Anesthesiology to 95% in Psychiatry. Expressions of confidence in first choices did not improve PPV. Sensitivity of asking for first choices increased with time; specificity was consistently high. USLME Step 1 scores were higher for students who ultimately trained in specialties more competitive than first-choice specialties at the end of year 2.
Specialty-oriented learning programs during medical school must accommodate students who change career plans. The PPV of specialty first choices improves each year, but even year 3 predictions can be inaccurate with potential loss of students from specialty-specific programs. USMLE Step 1 scores appeared to affect career plans expressed at the end of year 2.
Insulin secretory granules (SGs) mediate the regulated secretion of insulin, which is essential for glucose homeostasis. The basic machinery responsible for this regulated exocytosis consists of ...specific proteins present both at the plasma membrane and on insulin SGs. The protein composition of insulin SGs thus dictates their release properties, yet the mechanisms controlling insulin SG formation, which determine this molecular composition, remain poorly understood. VPS41, a component of the endolysosomal tethering homotypic fusion and vacuole protein sorting (HOPS) complex, was recently identified as a cytosolic factor involved in the formation of neuroendocrine and neuronal granules. We now find that VPS41 is required for insulin SG biogenesis and regulated insulin secretion. Loss of VPS41 in pancreatic β-cells leads to a reduction in insulin SG number, changes in their transmembrane protein composition, and defects in granule-regulated exocytosis. Exploring a human point mutation, identified in patients with neurological but no endocrine defects, we show that the effect on SG formation is independent of HOPS complex formation. Finally, we report that mice with a deletion of VPS41 specifically in β-cells develop diabetes due to severe depletion of insulin SG content and a defect in insulin secretion. In sum, our data demonstrate that VPS41 contributes to glucose homeostasis and metabolism.
Background
iGlebe is a fully automated internet treatment program for adults who stutter that has been shown, in some cases, to reduce anxiety and effectively manage social anxiety disorder for many ...participants. No such automated internet treatment program exists for adolescents who stutter.
Aims
The present paper reports a Phase I trial of an adolescent version of the adult program: iBroadway.
Methods & Procedures
Participants were 29 adolescents in the age range 12–17 years who were seeking cognitive–behaviour therapy (CBT) for anxiety associated with stuttering. The design was a non‐randomized Phase I trial with outcome assessments at pre‐treatment and immediately post‐treatment after 5 months of access to the program. No contact by a clinical psychologist occurred during participant use of the program. Outcomes were a range of psychological, quality‐of‐life and stuttering severity measures.
Outcomes & Results
The compliance rate for the seven iBroadway modules over 5 months was extremely favourable for internet CBT, at 52.4%. There was evidence of treatment effects for (1) the number of DSM‐IV mental health diagnoses with the Diagnostic Interview Schedule for Children; (2) the Unhelpful Thoughts and Beliefs About Stuttering scale; (3) the Subjective Units of Distress Scale; and (4) parent‐reported speech satisfaction.
Conclusions & Implications
Further development of iBroadway, the adolescent version of iGlebe, with Phase II trialling is warranted.
1. Assessing the causal factors underpinning the distribution and abundance of wildlife roadinduced mortality can be challenging. This is particularly ubiquitous for rare or elusive species, because ...traffic strikes occur infrequently for these populations and information about localized abundance, distribution and movements are generally lacking. Here, we assessed whether citizen-collected sightings data may serve as a low cost and efficient means of gathering long-term animal roadside presence and road-crossing information, which could then be used to assess the causative factors and direct mitigation actions aimed at reducing wildlife traffic strike frequency. 2. We explored this principle using two decades of traffic strike records and citizen-collected sightings of the southern cassowary Casuarius casuarius johnsonii. Roads have bisected the cassowaries' rain forest habitat and despite considerable investment into mitigation strategies for this species, road-induced mortality is considered one of the primary threatening processes affecting the population. 3. Using a Bayesian approach and controlling for spatial autocorrelation with conditional autoregressive models, we demonstrate that traffic strikes are primarily a density-dependent process in the southern cassowary. That is, traffic strike clusters occurred along stretches of road where cassowaries were most frequently sighted. There were, however, road stretches where traffic strike frequency was greater than predicted by the number of roadside sightings, illustrating when and where density-independent processes increased the mortality potential for a road-crossing cassowary. 4. Synthesis and applications. This is the first time that citizen-collected sightings data have been used to systematically inform upon the abundance and distribution of wildlife traffic strike. The technique not only predicts where incidents are likely to occur but also helps us to understand the factors responsible for strike clustering. While not a replacement for systematic surveys, we highlight citizen-collected sightings data as a low-cost option when assessing contributing factors to vehicle-induced mortality. Accounting for density-dependent and density-independent processes will ensure the most effective allocation of resources when implementing wildlife traffic strike mitigation.
Objective Maternal infection or inflammation may induce fetal inflammatory responses associated with fetal injury and cerebral palsy. We sought to assess the inflammation-associated neuroprotective ...potential of prophylactic N-acetyl-cysteine (NAC). We examined the effect of NAC on prevention of maternal lipopolysaccharide (LPS)-induced neonatal brain injury using magnetic resonance imaging. Study Design Pregnant Sprague Dawley dams (n = 5-8) at embryonic day 18 received intraperitoneal injection of LPS or saline at time 0. Animals were randomized to receive 2 intravenous injections of NAC or saline (time −30 and 120 minutes). Pups were delivered spontaneously and allowed to mature until postnatal day 25. Female offspring were examined by magnetic resonance brain imaging and analyzed using voxel-based analysis after spatial normalization. T2 relaxation time was used to assess white matter injury and diffusion tensor imaging for apparent diffusion coefficient (ADC) to assess white and gray matter injury. Results Offspring of LPS-treated dams exhibited significantly increased T2 levels and increased ADC levels in white and gray matter (eg, hypothalamus, motor cortex, corpus callosum, thalamus, hippocampus), consistent with diffuse cerebral injury. In contrast, offspring of NAC-treated LPS dams demonstrated similar T2 and ADC levels as control in both white and gray matter. Conclusion Maternal NAC treatment significantly reduced evidence of neonatal brain injury associated with maternal LPS. These studies suggest that maternal NAC therapy may be effective in human deliveries associated with maternal/fetal inflammation.
Objectives
The objective of this study was to evaluate the ability of
Lactobacillus curvatus
CRL705, CRL1532, and CRL1533 and
Lactobacillus sakei
CRL1613 to survive under simulated gastrointestinal ...conditions. Moreover, a microencapsulation approach was proposed to improve gastrointestinal survival. Finally, experiments were performed to demonstrate that
Lactobacill
us spp. can modulate the ability of
Listeria monocytogenes
FBUNT to adhere to and invade Caco-2 cells.
Results
Lactobacillus
strains were encapsulated in alginate beads to enhance the survival of bacteria under in vitro gastrointestinal conditions. All strains hydrolyzed bile salts using chenodeoxycholic acid as a substrate and adhered to Caco-2 cells. Cell-free supernatants (CFSs) showed antimicrobial activity against
L. monocytogenes
as demonstrated by agar diffusion assays. The average percentages of
L. monocytogenes
adhesion decreased from 67.74 to 41.75 and 38.7% in the presence of 50 and 90% (v/v), respectively, for all CFSs tested. The highest concentrations of CFSs completely inhibited the
L. monocytogenes
invasion of Caco-2 cells.
Conclusions
The studied
Lactobacillus
strains have protective effects against the adhesion and invasion of
L. monocytogenes
FBUNT. Alginate encapsulation of these bacteria improved gastrointestinal tolerance such that they could be further studied as potential probiotics against intestinal pathogenic bacteria.
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