Effect of feedback during virtual training of grip force control with a myoelectric prosthesis.
The aim of this study was to determine whether virtual training improves grip force control in prosthesis use, and to examine which type of augmented feedback facilitates its learning most. Thirty-two able-bodied participants trained grip force with a virtual ball-throwing game for five sessions in a two-week period, using a myoelectric simulator. They received either feedback on movement outcome or on movement execution. Sixteen controls received training that did not focus on force control. Variability over learning was examined with the Tolerance-Noise-Covariation approach, and the transfer of grip force control was assessed in five test-tasks that assessed different aspects of force control in a pretest, a posttest and a retention test. During training performance increased while the variability in performance was decreased, mainly by reduction in noise. Grip force control only improved in the test-tasks that provided information on performance. Starting the training with a task that required low force production showed no transfer of the learned grip force. Feedback on movement execution was detrimental to grip force control, whereas feedback on movement outcome enhanced transfer of grip force control to tasks other than trained. Clinical implications of these results regarding virtual training of grip force control are discussed.


Separation of amino acid enantiomers by micelle-enhanced ultrafiltration.
A Micelle-enhanced ultrafiltration (MEUF) separation process was investigated that can potentially be used for large-scale enantioseparations. Copper(II)-amino acid derivatives dissolved in nonionic surfactant micelles were used as chiral selectors for the separation of dilute racemic amino acids solutions. For the alpha-amino acids phenylalanine, phenylglycine, O-methyltyrosine, isoleucine, and leucine good separation was obtained using cholesteryl L-glutamate and Cu(II) ions as chiral selector with an operational enantioselectivity (alpha(op)) up to 14.5 for phenylglycine. From a wide set of substrates, including four beta-amino acids, it was concluded that the performance of this system is determined by two factors: the hydrophobicity of the racemic amino acid, which results in a partitioning of the racemic amino acid over micelle and aqueous solution, and the stability of the diastereomeric complex formed upon binding of the amino acid with the chiral selector. The chiral hydrophobic cholesteryl anchor of the chiral selector also plays an active role in the recognition process, since inversion of the chirality of the glutamate does not yield the reciprocal enantioselectivities. However, if the cholesteryl group is replaced by a nonchiral alkyl chain, reciprocal operational enantioselectivities are found with enantiomeric glutamate selectors.


Evolution of Complexity in Paleozoic Ammonoid Sutures.
The septal sutures of 588 genera of Paleozoic ammonoids showed a 1600 percent increase in mean complexity over 140 million years. Within 475 ancestor/descendant pairs, descendants were more than twice as likely to be more complex than their ancestors. Twelve subclades (373 genera) averaged 34 percent increased complexity. These patterns are compatible with an active or driven system of long-term bias for increased complexity. Mass extinctions acted in opposition to this long-term trend, tending to eliminate more-complex forms and resetting the trend with each extinction event.


Model-Based Clustering of Nonparametric Weighted Networks with Application to Water Pollution Analysis.
Water pollution is a major global environmental problem, and it poses a great environmental risk to public health and biological diversity. This work is motivated by assessing the potential environmental threat of coal mining through increased sulfate concentrations in river networks, which do not belong to any simple parametric distribution. However, existing network models mainly focus on binary or discrete networks and weighted networks with known parametric weight distributions. We propose a principled nonparametric weighted network model based on exponential-family random graph models and local likelihood estimation, and study its model-based clustering with application to large-scale water pollution network analysis. We do not require any parametric distribution assumption on network weights. The proposed method greatly extends the methodology and applicability of statistical network models. Furthermore, it is scalable to large and complex networks in large-scale environmental studies. The power of our proposed methods is demonstrated in simulation studies and a real application to sulfate pollution network analysis in Ohio watershed located in Pennsylvania, United States.


Estimating effective survey duration in camera trap distance sampling surveys.
Among other approaches, camera trap distance sampling (CTDS) is used to estimate animal abundance from unmarked populations. It was formulated for videos and observation distances are measured at predetermined 'snapshot moments'. Surveys recording still images with passive infrared motion sensors suffer from frequent periods where animals are not photographed, either because of technical delays before the camera can be triggered again (i.e. 'camera recovery time') or because they remain stationary and do not immediately retrigger the camera following camera recovery time (i.e. 'retrigger delays'). These effects need to be considered when calculating temporal survey effort to avoid downwardly biased abundance estimates. Here, we extend the CTDS model for passive infrared motion sensor recording of single images or short photo series. We propose estimating 'mean time intervals between triggers' as combined mean camera recovery time and mean retrigger delays from the time interval distribution of pairs of consecutive pictures, using a Gamma and Exponential function, respectively. We apply the approach to survey data on red deer, roe deer and wild boar. Mean time intervals between triggers were very similar when estimated empirically and when derived from the model-based approach. Depending on truncation times (i.e. the time interval between consecutive pictures beyond which data are discarded) and species, we estimated mean time intervals between retriggers between 8.28 and 15.05 s. Using a predefined snapshot interval, not accounting for these intervals, would lead to underestimated density by up to 96% due to overestimated temporal survey effort. The proposed approach is applicable to any taxa surveyed with camera traps. As programming of cameras to record still images is often preferred over video recording due to reduced consumption of energy and memory, we expect this approach to find broad application, also for other camera trap methods than CTDS.


A model for predicting nephrotoxicity in patients treated with aminoglycosides.
We have previously identified risk factors for nephrotoxicity in 204 patients receiving aminoglycosides. We added data on an additional 134 patients from the University of Chicago who were treated for longer periods (13.1 +/- 9.4 days) to determine if duration of therapy was also a risk factor. In the combined populations, nephrotoxicity developed in 59 (17.5%) of 338 patients, and duration of therapy was the factor most strongly associated with nephrotoxicity (P less than .0001). A new predictive model was developed that was then tested prospectively on 175 consecutive medical and surgical patients who had plasma levels of aminoglycoside measured. The new model accurately identified 14 of 15 patients with nephrotoxicity (sensitivity = 93%) and 106 of 160 without nephrotoxicity (specificity = 66%). A bedside scoring system accurately identified high-risk and low-risk patients. We believe these data add to the understanding of the clinical correlates of aminoglycoside nephrotoxicity and aid in the identification of high-risk patients.


Generation of the Y-chromosome linked red fluorescent protein transgenic mouse model and sexing at the preimplantation stage.
In mammals, sexual fate is determined by the chromosomes of the male and female gametes during fertilization. Males (XY) or females (XX) are produced when a sperm containing a Y or X-chromosome respectively fertilizes an X-chromosome-containing unfertilized egg. However, sexing of preimplantation stage embryos cannot be conducted visually. To address this, transgenic male mouse models with the ubiquitously expressed green fluorescent protein (GFP) transgene on X- (X-GFP) or Y-chromosomes (Y-GFP) have been established. However, when crossed with wild-type females, sexing of the preimplantation stage embryos by observing the GFP signal is problematic in some cases due to X-inactivation, loss of Y-chromosome (LOY), or loss of transgene fluorescence. In this study, a mouse model with the ubiquitously expressed red fluorescent protein (RFP) transgene on the Y-chromosome was generated since RFP is easily distinguishable from GFP signals. Unfortunately, the ubiquitously expressed tdTomato RFP transgene on the Y-chromosome (Y-RFP) mouse showed the lethal phenotype after birth. No lethal phenotypes were observed when the mitochondrial locating signal N-terminal of tdTomato (mtRFP) was included in the transgene construct. Almost half of the collected fertilized eggs from Y-mtRFP male mice crossed with wild-type females had an RFP signal at the preimplantation stage (E1.5). Therefore, XY eggs were recognized as RFP-positive embryos at the preimplantation stage. Furthermore, 100% sexing was observed at the preimplantation stage using the X-linked GFP/Y-linked RFP male mouse. The established Y-mtRFP mouse models may be used to study sex chromosome related research.


Middle-latency somatosensory evoked potentials after stimulation of the radial and median nerves: component structure and scalp topography.
Somatosensory evoked potentials (SEPs) after radial nerve stimulation are studied less frequently than those after median nerve stimulation. Therefore, little is known about their component structure and scalp topography. We investigated radial nerve SEPs after electrical stimulation at the left wrist. For comparison, the median nerve was also stimulated at the wrist. SEPs were recorded with 15 scalp electrodes (bandpass 0.5-200 Hz) in 27 healthy subjects. The waveform of the radial nerve SEP at a contralateral parietal lead was comparable to that of the median nerve SEP, consisting of P14, N20, P30, and N60. In spite of comparable stimulus intensities, SEP amplitudes were smaller after radial than after median nerve stimulation. Significant latency differences were found only for N20 (earlier for median nerve) and P30 (earlier for radial nerve). The duration of the primary complex N20-P30 thus was significantly shorter for the radial nerve. Whereas N20 and P30 were present with either earlobe or frontal reference, N60 had a prerolandic maximum and was best recorded with a bipolar transverse derivation. In addition, another middle-latency negativity (N110) was found near the secondary somatosensory cortex, which had previously been described only for radial nerve stimulation. In standard SEP derivations, the N110 is riding on the ascending limb of the vertex negativity. It could best be recorded in low temporal leads versus a midline reference. The scalp topographies of P30, N60, and N110 were similar for radial and median nerve stimulation.


Protocol of a randomised trial of teriparatide followed by zoledronic acid to reduce fracture risk in adults with osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare genetic disease associated with multiple fractures throughout life. It is often treated with osteoporosis medications but their effectiveness at preventing fractures is unknown. The Treatment of Osteogenesis Imperfecta with Parathyroid Hormone and Zoledronic Acid trial will determine if therapy with teriparatide (TPTD) followed by zoledronic acid (ZA) can reduce the risk of clinical fractures in OI. Individuals aged ≥18 years with a clinical diagnosis of OI are eligible to take part. At baseline, participants will undergo a spine X-ray, and have bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) at the spine and hip. Information on previous fractures and previous bone targeted treatments will be collected. Questionnaires will be completed to assess pain and other aspects of health-related quality of life (HRQoL). Participants will be randomised to receive a 2-year course of TPTD injections 20 µg daily followed by a single intravenous infusion of 5 mg ZA, or to receive standard care, which will exclude the use of bone anabolic drugs. Participants will be followed up annually, have a repeat DXA at 2 years and at the end of study. Spine X-rays will be repeated at the end of study. The duration of follow-up will range between 2 and 8 years. The primary endpoint will be new clinical fractures confirmed by X-ray or other imaging. Secondary endpoints will include participant reported fractures, BMD and changes in pain and HRQoL. The study received ethical approval in December 2016. Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results will inform clinical practice by determining if TPTD/ZA can reduce the risk of fractures in OI compared with standard care. ISRCTN15313991.


Diffusion tensor imaging of the pediatric spinal cord at 1.5T: preliminary results.
Recent studies suggest that pediatric subjects as old as 8-years-of-age may have difficulty with the ISNCSCI examinations. Our aim was to investigate DTI parameters of healthy spinal cord in children with noncervical IS for comparison with children with SCI and to prospectively evaluate reliability measures of DTI and to correlate the measures obtained in children with SCI with the ISNCSCI. Five controls with thoracic and lumbar IS and 5 children with cervical SCI were imaged twice by using a single-shot echo-planar diffusion-weighted sequence. Axial imaging was performed to cover the entire cervical spinal cord in controls. For the SCI subjects, 2 vertebral bodies above and below the injury were imaged. FA and D values were obtained at different levels of the cervical spinal cord. All subjects with SCI had undergone ISNCSCI clinical examinations. Statistical analysis was performed to access differences of the DTI indices between the controls and SCI subjects, reproducibility measurements, and correlations between DTI and ISNCSCI. Subjects with SCI showed reduced FA and increased D values compared with controls. Test-retest reproducibility showed good ICC coefficients in all the DTI index values among controls (≥0.9), while the SCI group showed moderate ICC (≥0.77). There were statistically significant correlations between the various DTI indices and ISNCSCI scores. Preliminary DTI indices in children were determined and showed good reproducibility. Reduced FA and increased D values were seen in children with SCI in comparison with controls and showed good clinical correlation with ISNCSCI examinations.


Effects of a family involvement program in patients with central-line insertion.
The purpose of this study was to evaluate the effects of family-involved care on caregivers' self-efficacy, the degree of satisfaction with central-line care, and the occurrence of central-line-associated bloodstream infections (CLABSIs). We adopted a pretest-posttest quasi-experimental design, recruiting 62 participants from 2009 to 2010. Family caregivers in the experimental group received instructional guidance before collaboratively participating in patient care, whereas the control group received routine care. Our results indicated that in both groups, the overall posttest scores for self-efficacy were significantly higher than the pretest scores. The score for the question "When the patient moves around, how confident are you with ensuring catheter safety?" was significantly higher in the experimental group than in the control group. Satisfaction with the provision of central-line care was also significantly higher in the experimental group than in the control group. CLABSIs did not occur in either group of patients.


Immunohistochemical Expression of Leptin in Non Melanoma Skin Cancer.
Obesity in adults is associated with numerous health disorders including some forms of cancer. Various epidemiological studies have found a link between excess adiposity and malignant melanoma; however, the association with non melanoma skin cancer is questionable. Leptin is a hormone produced mainly by the adipose tissue and its serum level may reflect body mass index. Leptin is reported to promote proliferation and angiogenesis and deregulate apoptosis, therefore facilitates the process of carcinogenesis. The current study tried to assess leptin localization and expression in non melanoma skin cancer to verify its possible role in pathogenesis of this cancer. This study was carried out on 13 Basal Cell Carcinoma (BCC) cases and 14 Squamous Cell Carcinoma (SCC) cases together with 19 normal skin biopsies as a control group using immunohistochemical method. Leptin was expressed in 52.6% of the normal epidermis with pure cytoplasmic and both cytoplasmic and nuclear staining patterns. All cases of SCC (100%) and two cases of BCC (15.4%) showed leptin expression in tumour cells whereas nuclear expression was in favour of SCC. Stromal expression of leptin was seen in both SCC (57.1%) and BCC (38.5%) without significant differences. Percentage of leptin expression by tumour cells in SCC showed positive linear correlation with tumour size (p=0.02) and microvessel density (p=0.000). Stromal expression of leptin in SCC was associated with large tumour size (p=0.04), advanced stage (p=0.01) and tumours arising in sites other than head and neck (p=0.01). Leptin could have a more important role in pathogenesis of cutaneous SCC rather than BCC that may reflect the trivial role of obesity in induction of BCC. The expression of leptin by tumour and stromal cells of SCC could co-operate in its progression by promoting angiogenesis with subsequently acquiring large tumour size and then advanced stage.


Why we need to report more than 'Data were Analyzed by t-tests or ANOVA'.
Transparent reporting is essential for the critical evaluation of studies. However, the reporting of statistical methods for studies in the biomedical sciences is often limited. This systematic review examines the quality of reporting for two statistical tests, t-tests and ANOVA, for papers published in a selection of physiology journals in June 2017. Of the 328 original research articles examined, 277 (84.5%) included an ANOVA or t-test or both. However, papers in our sample were routinely missing essential information about both types of tests: 213 papers (95% of the papers that used ANOVA) did not contain the information needed to determine what type of ANOVA was performed, and 26.7% of papers did not specify what post-hoc test was performed. Most papers also omitted the information needed to verify ANOVA results. Essential information about t-tests was also missing in many papers. We conclude by discussing measures that could be taken to improve the quality of reporting.


Aggression and the brain monoamines: what are the answers, but of more importance what are the questions...?
Experiments involving three models of aggression (shock-induced fighting, ranacide and septal lesion-induced hyperirritability) are employed to demonstrate classically different sub-types of aggressive behavior. These categories are shown to be distinct entities when compared on the basis of hormonal dependency, central anatomical and peripheral autonomic involvement and inhibition or enhancement through pharmacological manipulations. Investigations into brain monoamine functioning (norepinephrine, dopamine and serotonin) demonstrate the heterogeneity of correlations which may exist between aggressive behaviors and brain amines. Data are analyzed on the basis of individual amine alterations and changes in monoaminergic neuronal balances. Thus, higher levels of shock-induced aggressive behavior is associated with higher NE/5-HT and DA/K-HT ratioes whereas similar alterations in these biochemical indices occur without observable changes in ranacide behavior. Septal lesion induced hyperirritability is correlated with precisely opposite aminergic changes, namely, decreases in NE/5-HT ratioes. These results demonstrate the necessity of precise aggressive model evaluation prior to attempts at biochemical mechanism elucidation.


Eigen decomposition solution to the one-dimensional time-dependent photon transport equation.
The time-dependent one-dimensional photon transport (radiative transfer) equation is widely used to model light propagation through turbid media with a slab geometry, in a vast number of disciplines. Several numerical and semi-analytical techniques are available to accurately solve this equation. In this work we propose a novel efficient solution technique based on eigen decomposition of the vectorized version of the photon transport equation. Using clever transformations, the four variable integro-differential equation is reduced to a set of first order ordinary differential equations using a combination of a spectral method and the discrete ordinates method. An eigen decomposition approach is then utilized to obtain the closed-form solution of this reduced set of ordinary differential equations.


Discussing and prescribing expensive unfunded anticancer drugs in Australia.
Australia has a publicly funded universal healthcare system which heavily subsidises the cost of most registered anticancer drugs. The use of anticancer drugs that are unfunded, that is, not subsidised by the government, entails substantial out-of-pocket costs for patients. We sought to determine how frequently Australian medical oncologists discuss and prescribe unfunded anticancer drugs, and their attitudes and beliefs about their use. Members of the Medical Oncology Group of Australia (MOGA) completed an online survey about their clinical practices over a recent 3-month period. A negative binomial regression model was used to examine the influence of respondent characteristics on the rate of discussions about, and prescription of, unfunded anticancer drugs. Of the 154 respondents (27% of 575 MOGA members), 92% had discussed and 68% had prescribed at least one unfunded anticancer drug in the last 3 months. Respondents reported discussing unfunded anticancer drugs with an average of 2.5 patients per month (95% CI 2.1 to 2.9), and prescribed them to an average of 0.9 patients per month (95% CI 0.7 to 1.2). The rate of discussing unfunded anticancer drugs was associated with being fully qualified (p=0.01), and being in a metropolitan practice (p=0.009), the rate of prescription was associated only with being in metropolitan practice (p=0.006). The concerns about discussing and prescribing unfunded anticancer drugs rated most important were as follows: 'potential to cause financial hardship' and 'difficulty for patients to evaluate the benefits versus the costs'. Australian medical oncologists frequently discuss and prescribe unfunded anticancer drugs, and are concerned about their patients having to face difficult decisions and financial hardship. Further research is needed to better understand the factors that affect how oncologists and patients value expensive, unfunded anticancer drugs.


tRNA leucine identity and recognition sets.
Transfer RNAs (tRNAs) are grouped into two classes based on the structure of their variable loop. In Escherichia coli, tRNAs from three isoaccepting groups are classified as type II. Leucine tRNAs comprise one such group. We used both in vivo and in vitro approaches to determine the nucleotides that are required for tRNA(Leu) function. In addition, to investigate the role of the tRNA fold, we compared the in vivo and in vitro characteristics of type I tRNA(Leu) variants with their type II counterparts.A minimum of six conserved tRNA(Leu) nucleotides were required to change the amino acid identity and recognition of a type II tRNA(Ser) amber suppressor from a serine to a leucine residue. Five of these nucleotides affect tRNA tertiary structure; the G15-C48 tertiary "Levitt base-pair" in tRNA(Ser) was changed to A15-U48; the number of nucleotides in the alpha and beta regions of the D-loop was changed to achieve the positioning of G18 and G19 that is found in all tRNA(Leu); a base was inserted at position 47n between the base-paired extra stem and the T-stem; in addition the G73 "discriminator" base of tRNA(Ser) was changed to A73. This minimally altered tRNA(Ser) exclusively inserted leucine residues and was an excellent in vitro substrate for LeuRS. In a parallel experiment, nucleotide substitutions were made in a glutamine-inserting type I tRNA (RNA(SerDelta); an amber suppressor in which the tRNA(Ser) type II extra-stem-loop is replaced by a consensus type I loop). This "type I" swap experiment was successful both in vivo and in vitro but required more nucleotide substitutions than did the type II swap. The type I and II swaps revealed differences in the contributions of the tRNA(Leu) acceptor stem base-pairs to tRNA(Leu) function: in the type I, but not the type II fold, leucine specificity was contingent on the presence of the tRNA(Leu) acceptor stem sequence. The type I and II tRNAs used in this study differed only in the sequence and structure of the variable loop. By altering this loop, and thereby possibly introducing subtle changes into the overall tRNA fold, it became possible to detect otherwise cryptic contributions of the acceptor stem sequence to recognition by LeuRS. Possible reasons for this effect are discussed.


Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.
Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.


Application of item response theory for development of a global functioning measure of dementia with linear measurement properties.
An ideal measure of global functioning for patients with dementia would discriminate at very high and very low levels of functioning and would have linear measurement properties such that a given change in score corresponds to the same amount of change in underlying ability at any part of the ability continuum. Using item response theory methods, linearity of test measurement can be directly assessed and items can be selected to construct a test with desired measurement characteristics. The purpose of this study was to apply item response theory methods to evaluating and developing global functioning scales. Subjects were 1207 patients who had received comprehensive dementia evaluations. Items were selected from two measures of cognitive functioning (Mini Mental State Examination, MMS; Blessed Information Memory Concentration Test, BIMCT) and one measure of independent functioning (Blessed-Roth Dementia Rating Scale, BRDRS). The MMS and BIMCT showed significant non-linearity of measurement, especially at low and high ability levels. A brief composite measure was created by selecting from the three instruments 25 items that fit a uniform distribution of item difficulty across the entire range of ability measured by the three instruments. This composite measure and the BRDRS showed better linearity of measurement than the other two instruments. Results have implications for development of a psychometrically sophisticated, brief measure of global functioning for clinical and research use in dementia.


Generation of energy from salinity gradients using capacitive reverse electro dialysis: a review.
Energy is one of the critical resources determining the overall socioeconomic development. Global warming and natural resource demand had made the world to look into renewable energy like solar, wind, and fuel cells. Salinity gradient energy is the concept of extraction of energy from the concentration gradient between saline and clean solution. In this review, we present different novel systems to generate electricity by salinity gradients by reverse electrodialysis technology integrated with capacitive electrodes and also different types of reverse electro dialysis. This capacitive reverse electrodialysis system synergistically combines previous developments in capacitive mixing and reverse electrodialysis. This review work consists of the study of various reverse electrodialyses, comparing the recent advancements with the novel process and integrates the various results and experiments, and reviews of all reverse electrodialysis are incorporated.


Data-Adaptive 2-D Tracking Doppler for High-Resolution Spectral Estimation.
Spectral broadening in pulsed-wave Doppler caused by the transit-time effect deteriorates the frequency resolution and may cause overestimation of maximum velocities in high-velocity blood flow regions and for large beam-to-flow angles. Data-adaptive spectral estimators have been shown to provide improved frequency resolution, especially for small ensemble lengths, but offer little or no improvement when the transit-time effect dominates. In this work, a method is presented that combines a data-adaptive spectral estimation method, the power spectral Capon, and 2-D tracking Doppler to enable improved frequency resolution for both high and low velocities. For each velocity, a time signal is extracted by tracking scatterers over time and space to decrease the transit-time effect, and power spectral Capon is used for spectral estimation. The method is evaluated using simulations, flow phantom recordings, and recordings from healthy and stenotic carotid arteries. Simulation results showed that the spectral width was decreased by 60% compared to 2-D tracking Doppler for velocities around 2.3 m/s using 12 time samples. The reduction was estimated to be 66% using the flow phantom results for 0.85-m/s mean velocity. A 5-dB SNR gain was observed from the in vivo results compared with Welch's method. Computer simulations confirm that in the presence of velocity gradients or out-of-plane motion, the proposed method can be used to reduce spectral broadening by requiring shorter observation windows.


Role of translation and attenuation in the control of pyrBI operon expression in Escherichia coli K-12.
Expression of the pyrBI operon of Escherichia coli K-12, which encodes the subunits of the pyrimidine biosynthetic enzyme aspartate transcarbamylase, is negatively regulated by the intracellular levels of UTP. Previous experiments suggested a unique model for regulation of operon expression in which low UTP levels cause close coupling of transcription and translation of the pyrBI leader region. This close coupling suppresses transcriptional termination at an attenuator preceding the structural genes. In this study, we examined the regulatory role of translation and attenuation in operon expression. To determine whether the leader region is translated, we constructed a plasmid, designated pBHM17, in which the pyrBI promoter(s) and the first 11 codons for a putative 44-amino acid leader polypeptide are fused to codon 9 of lacZ. A transformant carrying this plasmid synthesized a beta-galactosidase fusion protein with the amino-terminal sequence of the leader polypeptide, demonstrating that the signals required for leader polypeptide synthesis function in vivo. Synthesis of the fusion protein was nearly insensitive to pyrimidine availability. In uracil-grown cells, the level of fusion protein synthesis encoded by plasmid pBHM17 was much greater than that encoded by a similar plasmid containing a pyrB::lacZ gene fusion, in which the pyrBI promoter-regulatory region is intact. These results indicate that the downstream leader sequence which includes the attenuator is required for regulation and functions as a transcriptional barrier. Oligonucleotide-directed mutagenesis was used to change the ATG leader polypeptide initiation codon of the intact pyrBI operon to ACG, which was shown to strongly inhibit translational initiation. This mutation greatly reduced operon expression and regulation as predicted by the attenuation control model.


The role of mast cells in functional GI disorders.
Functional gastrointestinal disorders (FGIDs) are characterized by chronic complaints arising from disorganized brain-gut interactions leading to dysmotility and hypersensitivity. The two most prevalent FGIDs, affecting up to 16-26% of worldwide population, are functional dyspepsia and irritable bowel syndrome. Their etiopathogenic mechanisms remain unclear, however, recent observations reveal low-grade mucosal inflammation and immune activation, in association with impaired epithelial barrier function and aberrant neuronal sensitivity. These findings come to challenge the traditional view of FGIDs as pure functional disorders, and relate the origin to a tangible organic substrate. The mucosal inflammatory infiltrate is dominated by mast cells, eosinophils and intraepithelial lymphocytes in the intestine of FGIDs. It is well established that mast cell activation can generate epithelial and neuro-muscular dysfunction and promote visceral hypersensitivity and altered motility patterns in FGIDs, postoperative ileus, food allergy and inflammatory bowel disease. This review will discuss the role of mucosal mast cells in the gastrointestinal tract with a specific focus on recent advances in disease mechanisms and clinical management in irritable bowel syndrome and functional dyspepsia.


Initiating antiretroviral treatment for newly diagnosed HIV patients in sexual health clinics greatly improves timeliness of viral suppression.
The 'JumpstART' program in New York City (NYC) public Sexual Health Clinics (SHC) provides patients newly diagnosed with human immunodeficiency virus (HIV) with antiretroviral medication (ART) (1-month supply) on day of diagnosis and active linkage to HIV care (LTC). We examined viral suppression (VS) among patients who did and did not receive JumpstART services. Retrospective cohort. Among newly diagnosed SHC patients (23 November 2016-30 September 2018) who were matched to the NYC HIV surveillance registry to obtain HIV laboratory test results through 30 June 2019, we compared 230 JumpstART and 73 non-JumpstART patients regarding timely LTC (≤30 days), probability of VS (viral load < 200 copies/ml) by 3 months post-diagnosis, and time to and factors associated with achieving VS within the follow-up period. Of 303 patients, 76% (230/303) were JumpstART and the remaining were non-JumpstART patients; 36 (11%) had acute HIV infections. LTC ≤30 days was observed for 63% of JumpstART and 73% of non-JumpstART patients. By 3 months post-diagnosis, 83% of JumpstART versus 45% of non-JumpstART patients achieved VS (log-rank, P < .0001). Median times to VS among virally suppressed JumpstART and non-JumpstART patients were 31 (interquartile range [IQR]: 24-51) and 95 days (IQR: 52-153), respectively. For groups with and without timely LTC, JumpstART was associated with viral suppression within 3 months post-diagnosis, after adjusting for age and baseline viral load. Prompt ART initiation among SHC patients, some with acute HIV infections, resulted in markedly shortened intervals to VS. Immediate ART provision and active LTC can be key contributors to improved HIV treatment outcomes and the treatment-as-prevention paradigm, with potential for downstream, population-level benefit.


Reduction of Fermi level pinning at Cu-BP interfaces by atomic passivation.
Black phosphorus (BP) is a semiconducting material with a direct finite band gap in its monolayer, attracting intense attention for its application in field-effect transistors. However, strong Fermi level pinning (FLP) has been observed for contacts between BP and high work function metals, e.g., Cu. Such FLP presents an undesirable hurdle preventing the achievement of high performance field-effect devices. In this regard, there is a crucial need to understand the FLP occurring at the metal-BP interfaces and explore the possibility to reduce it. The present work studied atomic passivation in reducing FLP for the Cu-BP system using density functional theory calculations. The passivation by H, N, F, S, and Cl atoms on the Cu(111) surface has been considered. The results showed that the passivated atoms can shield the direct contact between Cu(111) and BP, thus reducing FLP at Cu-BP interfaces. In particular, S and Cl atoms were found to be highly effective agents to achieve a significant reduction of FLP, leading to Cu-BP contacts with ultralow Schottky barrier height (SBH) and suggesting the possibility of ohmic contact formation. Our findings demonstrate surface passivation as an effective method towards depinning the Fermi level at the metal-BP interface and subsequently controlling the SBH for BP-based electronic devices.


Isolation, identification, and partial cDNA cloning of genomic RNA of jaagsiekte retrovirus, the etiological agent of sheep pulmonary adenomatosis.
The genome of the jaagsiekte (JS) retrovirus (JSRV), the etiological agent of sheep pulmonary adenomatosis (jaagsiekte), has been identified, isolated, and partly cloned. The JSRV genome is ca. 8.7 kb long. cDNA of the genomic RNA was synthesized and cloned. A clone, JS 46.1, was isolated and characterized. It has an insert of 2.1 kb which hybridizes to the same 8.7-kb RNA in all the JSRV-infected sheep lung washes tested but does not hybridize to maedi-visna virus, a sheep lentivirus often found coinfecting JSRV-infected lungs. Comparison of the amino acid sequence encoded by JS 46.1 with those encoded by other retroviruses revealed that JSRV has homology to the type D and B oncoviruses and to human endogenous retrovirus.


Prenatal screening for major congenital heart disease: assessing performance by combining national cardiac audit with maternity data.
Determine maternity hospital and lesion-specific prenatal detection rates of major congenital heart disease (mCHD) for hospitals referring prenatally and postnatally to one Congenital Cardiac Centre, and assess interhospital relative performance (relative risk, RR). We manually linked maternity data (3 hospitals prospectively and another 16 retrospectively) with admissions, fetal diagnostic and surgical cardiac data from one Congenital Cardiac Centre. This Centre submits verified information to National Institute for Cardiovascular Outcomes Research (NICOR-Congenital), which publishes aggregate antenatal diagnosis data from infant surgical procedures. We included 120 198 unselected women screened prospectively over 11 years in 3 maternity hospitals (A, B, C). Hospital A: colocated with fetal medicine, proactive superintendent, on-site training, case-review and audit, hospital B: on-site training, proactive superintendent, monthly telemedicine clinics, and hospital C: sonographers supported by local obstetrician. We then studied 321 infants undergoing surgery for complete transposition (transposition of the great arteries (TGA), n=157) and isolated aortic coarctation (CoA, n=164) screened in hospitals A, B, C prospectively, and 16 hospitals retrospectively. 385 mCHD recorded prospectively from 120 198 (3.2/1000) screened women in 3 hospitals. Interhospital relative performance (RR) in Hospital A:1.68 (1.4 to 2.0), B:0.70 (0.54 to 0.91), C:0.65 (0.5 to 0.8). Standardised prenatal detection rates (funnel plots) demonstrating inter-hospital variation across 19 hospitals for TGA (37%, 0.00 to 0.81) and CoA (34%, 0.00 to 1.06). Manually linking data sources produced hospital-specific and lesion-specific prenatal mCHD detection rates. More granular, rather than aggregate, data provides meaningful feedback to improve screening performance. Automatic maternal and infant record linkage on a national scale, requires verified, prospective maternity audit and integration of health information systems.


[Epidemiological surveillance of dental fluorosis in a city with a tropical climate with a fluoridated public drinking water supply].
The scope of this study was to evaluate the prevalence and severity of dental fluorosis among 11 to 14-year-old schoolchildren in Teresina, Piauí, Brazil, which is a tropical city with a fluoridated public drinking water supply. It involved a cross-sectional observational study on a sample of 571 students in public and private schools. Informed Consent forms were approved for the data collection and the exams were conducted at the schools. Data were recorded on a questionnaire answered by the parents, regarding the socioeconomic and demographic characteristics and oral hygiene habits of the sample. The dental exam was performed qualified dental sugeons. The Thylstrup-Fejerskov (TF) index was used. The prevalence of fluorosis was 77.9%, and only 12.5% of the affected children had TF ≥ grade 3 (with aesthetic damage). The premolars were the teeth most affected by fluorosis. Among the students with the highest severity of fluorosis, 98.6% belonged to the lowest social bracket (> B2), 91.5% were born and had always lived in Teresina, 94.4% consumed water from the fluoridated public supply, 76% used toothpaste for children and 64% of mothers reported that they swallowed toothpaste. The prevalence of fluorosis was high, though the severity was low in individuals exposed to fluoridation since birth.


Physiologically based absorption modeling to predict bioequivalence of controlled release and immediate release oral products.
Physiologically based absorption modeling was conducted to predict bioequivalence (BE) for immediate release (IR) and controlled release (CR) formulations. In case of the CR formulation of a BCS class 1 drug, sensitivity analyses were conducted to investigate the impact of gastrointestinal (GI) transit time and absorption scaling factors in caecum and colon on formulation PK. The regional absorption profiles of the test and reference formulations were compared to provide additional confidence on the BE predictions. For IR formulation of BCS class 2b drug, the sensitivity of dissolution rate, precipitation time and human permeability were evaluated. Finally for both cases, population simulations were conducted in crossover manner to investigate BE between formulations, and compared with the observed data. These case studies highlight the utility of absorption modeling in prediction of BE. Such modeling can be used for development of innovator and generic products, as well as to address questions arising during regulatory reviews.


Phenotypic features of epilepsy due to sodium channelopathies - A single center experience from India.
Nearly 40% of pediatric epilepsies have a genetic basis. There is significant phenotypic and genotypic heterogeneity, especially in epilepsy syndromes caused by sodium channelopathies. Sodium channel subunit 1A (SCN1A)-related epilepsy represents the archetypical channel-associated gene that has been linked to a wide spectrum of epilepsies of varying severity. Subsequently, other sodium channels have also been implicated in epilepsy and other neurodevelopmental disorders. This study aims to describe the phenotypes in children with sodium channelopathies from a center in Southern India. This is a retrospective, descriptive, and single-center study. Out of 112 children presenting with epilepsy who underwent genetic testing between 2017 and 2021, 23 probands (M: F = 12:11) were identified to have clinically significant sodium channel mutations. Clinical presentation, electroencephalography, and imaging features of these patients were recorded. The utility of genetic test results (e.g., in planning another child, withdrawal of medications, or change in treatment) was also recorded. Age at onset of seizures ranged from day 4 of life to 3.5 years. Clinical epilepsy syndromes included generalized epilepsy with febrile seizures plus (n = 3), Dravet syndrome (n = 5), early infantile epileptic encephalopathy (n = 7), drug-resistant epilepsy (n = 5), and epilepsy with associated movement disorders (n = 3). The most common type of seizure was focal with impaired awareness (n = 18, 78.2%), followed by myoclonic jerks (n = 8, 34.78%), epileptic spasms (n = 7, 30.4%), bilateral tonic-clonic seizures/generalized tonic-clonic seizures (n = 3, 13%), and atonic seizures (n = 5, 23.8%). In addition to epilepsy, other phenotypic features that were discerned were microcephaly (n = 1), cerebellar ataxia (n = 2), and chorea and dystonia (n = 1). Sodium channelopathies may present with seizure phenotypes that vary in severity. In addition to epilepsy, patients may also have other clinical features such as movement disorders. Early clinical diagnosis may aid in tailoring treatment for the given patient.


[AIDS cases in the rural area in Mexico].
The objective of this paper is to describe the AIDS epidemic in rural areas of Mexico. Information from the National AIDS Registry and the 1990 XI National Census was used. Rural AIDS cases and urban cases were compared regarding notification time, sex, risk categories and migration information. Of the 19,090 AIDS cases reported to the first of July 1994, 699 (3.7%) were rural cases. The first five of these cases were reported in 1986, three years after the first cases had been reported in Mexico. The number of AIDS cases has been growing each year but in 1991. Cases have been reported by all Mexican states. The state with the highest prevalence was Nayarit with 102 cases per million inhabitants, followed by Morelos with 99, Jalisco with 90, and Colima and Tlaxcala with 84. A total of 25% of the rural cases are migrants who have been to the US, against 6.1% of cases from urban areas. The distribution by sex shows 21.3% of women affected against 14.4% of urban cases (p < 0.05). The rural female to male ratio is 1:4, while the urban ratio is 1:6. The prevalence rates are almost three times greater in men than in women. The rural AIDS pattern represents a problem not because of the number of people affected but because of the heterosexual way of transmission. We do not think that migration to the US is going to change. The rural AIDS epidemic is more recent and growing faster than that occurring in the urban setting.


Perioperative blood product administration and thromboembolic events in patients with treated polycythemia vera: a case-control study.
Patients with polycythemia vera (PV) have historically been considered to be at high risk for perioperative hemorrhagic and thromboembolic complications. However, no recent studies have compared these outcomes between treated PV patients and patients without PV undergoing similar procedures. Patients with PV who underwent surgery with anesthesia from June 1, 2006, to May 31, 2011, were randomly matched (sex, age, type of surgical procedure, surgical year) at a ratio of 1:4 with control patients without PV. Conditional logistic regression analysis adjusting for surgical duration, preoperative hemoglobin, platelet count, and cardiovascular disease was used to assess the association between PV and blood product transfusions, thromboembolism, and other major cardiovascular and pulmonary complications. Fifty-six PV patients who underwent 79 surgeries were matched with 312 controls. During hospitalization, 35 (44.3%) and 82 (25.9%) PV and control patients, respectively, were transfused with blood products. PV patients were at increased risk for transfusion intraoperatively (odds ratio [OR], 4.35; 95% confidence interval [CI], 1.79-10.57; p = 0.001) and during hospitalization (OR, 4.35; 95% CI, 1.84-10.31; p < 0.001). The likelihood of thromboembolic complications and/or other major complications did not differ between the two study groups (thromboembolic-OR 1.53, 95% CI 0.39-6.02, p = 0.540; other major complications-OR 2.15, 95% CI 0.93-4.96, p = 0.073). Medically managed PV patients had an increased likelihood of receiving blood products perioperatively. Given the low number of observed thromboembolic events, we cannot make definitive conclusions regarding the association between PV and thromboembolism.


[Cylindroma of the base of the skull with longstanding neurological disturbances. Anatomo-clinical correlation].
The authors present the clinico-pathological correlation in a women who developed at the age of 43 years progressive pain in the left hemiface with motor and sensitive disorders of the left trigeminal nerve. Progressive involvement of the left IIIrd, IVth and Vth cranial nerves appeared with persistence of intractable facial pain which was not responsive to treatment by Tegretol, nor by thermocoagulation of the left Gasserian ganglion. Partial resection of a tumor was performed. The biopsy revealed its cylindromatous nature. The patient died after eight years of evolution. Autopsy confirmed an extensive tumoral invasion of the left temporal bone with invasion of the dura, the left cavernous sinus, and tumoral infiltration of the IIIrd, IVth, Vth and VIIIth cranial nerves on the left side. Metastases of the cylindromatous epithelioma were found in the liver and adrenals. The precise origin of the tumor could not be ascertained.


Mediating role of psychological distress in the associations between neighborhood social environments and sleep health.
The characteristics of neighborhood social environments, such as safety and social cohesion, have been examined as determinants of poor sleep. The current study investigates associations between neighborhood social characteristics and sleep health, as well as the mediating role of psychological distress on these possible associations. Three waves of PHRESH Zzz (n = 2699), a longitudinal study conducted in two low-income, predominately Black neighborhoods, were utilized for this analysis. The characteristics of neighborhood social environments were measured using crime rates, a neighborhood social disorder index, and self-reported social cohesion. Sleep health was measured via 7 days of wrist-worn actigraphy as insufficient sleep, sleep duration, wake after sleep onset (WASO), and sleep efficiency. G-estimations based on structural nested mean models and mediation analyses were performed to estimate the effects of neighborhood social environments on sleep as well as direct/indirect effects through psychological distress. Crime rate around residential addresses was associated with increased risk of insufficient sleep (risk ratio: 1.05 [1.02, 1.12]), increased WASO (β: 3.73 [0.26, 6.04]), and decreased sleep efficiency (β: -0.54 [-0.91, -0.09]). Perceived social cohesion was associated with decreased risk of insufficient sleep (OR: 0.93 [0.88, 0.97]). Psychological distress mediated part of the associations of crime and social cohesion with insufficient sleep. Neighborhood social environments may contribute to poor sleep health in low-income, predominantly Black neighborhoods, and psychological distress can be a salient pathway linking these neighborhood characteristics and sleep health.


Study of laryngopharyngeal pathology in Thoroughbred horses in southern California.
There is increasing anecdotal evidence among horse owners, trainers and equine clinicians of a high prevalence of subepiglottic ulcers, suggested to have a negative effect on racing performance. To provide a prevalence study and pathological characterisation of laryngopharyngeal lesions with emphasis in the subepiglottic area and, in particular, subepiglottic ulcers. The study was carried out on 91 Thoroughbred racehorses received for post mortem examination from 4 major Southern California racetracks. The most common reason for submission was catastrophic musculoskeletal injury, but others include sudden death, laminitis, colic, colitis, neurological disorders, pleuropneumonia and arytenoid chondropathy. Laryngopharyngeal specimens were collected and examined grossly; selected cases were also examined histopathologically. Thirteen horses (143%) had at least one type of laryngopharyngeal abnormality, 7 horses (7.7%) had lesions in the subepiglottic soft tissues, including 4 subepiglottic ulcers, 2 soft palate 'kissing lesions' and one 'subepiglottic scar'. Eight horses (8.8%) had lesions elsewhere in the laryngopharynx, including mucosal ulcerations, arytenoid chondropathy, epiglottic entrapment and partial absence of arytenoid cartilage. Lesions in the subepiglottic area were among the most prevalent in this study, suggesting that an important percentage of laryngopharyngeal abnormalities may be missed during routine endoscopy of the standing horse, which often does not include the examination of subepiglottic tissues. Pathologically, subepiglottic ulcers were chronic-active with viable hyperplastic epithelial margins, suggesting that proper healing and re-epithelialisation should occur with appropriate treatment. In most cases, the lesions observed do not necessarily indicate a clinical problem and more extensive prevalence studies and correlation between abnormalities found and performance are needed to assess the clinical relevance of subepiglottic soft tissue lesions accurately.


Host traits and environment interact to determine persistence of bat populations impacted by white-nose syndrome.
Emerging infectious diseases have resulted in severe population declines across diverse taxa. In some instances, despite attributes associated with high extinction risk, disease emergence and host declines are followed by host stabilisation for unknown reasons. While host, pathogen, and the environment are recognised as important factors that interact to determine host-pathogen coexistence, they are often considered independently. Here, we use a translocation experiment to disentangle the role of host traits and environmental conditions in driving the persistence of remnant bat populations a decade after they declined 70-99% due to white-nose syndrome and subsequently stabilised. While survival was significantly higher than during the initial epidemic within all sites, protection from severe disease only existed within a narrow environmental space, suggesting host traits conducive to surviving disease are highly environmentally dependent. Ultimately, population persistence following pathogen invasion is the product of host-pathogen interactions that vary across a patchwork of environments.


Corrigendum to: Paternal priming of maternal tissues to optimise pregnancy success.
The question of 'how does the allogeneic fetus survive gestation in the face of the maternal immune system?' has yet to be definitively answered. Several acceptable mechanisms exist to facilitate survival of the semi-allogeneic fetus in various species; paramount is the immunological separation of maternal and fetal tissues during gestation. However, keen observation of the maternal immune system during pregnancy has noted maternal immune tolerance to paternal-specific antigens. A mechanism by which the maternal immune system tolerates specific paternal antigens expressed on the fetus would be far more beneficial than the previously proposed immune indolence that would leave the mother susceptible to infection. In species like human or rodent, implantation occurs days after fertilisation and, as such, the mechanisms to establish antigen-specific tolerance must be initiated very early during pregnancy. We and others propose that these mechanisms are initiated at the time of insemination when paternal antigens are first introduced to the maternal immune system. Indeed, a new paradigm demonstrating the importance of paternal-maternal communication at the time of insemination is becoming evident as it relates to maternal tolerance to fetal antigen and ultimately pregnancy success.


Activation of dopaminergic D2/D3 receptors modulates dorsoventral connectivity in the hippocampus and reverses the impairment of working memory after nerve injury.
Dopamine plays an important role in several forms of synaptic plasticity in the hippocampus, a crucial brain structure for working memory (WM) functioning. In this study, we evaluated whether the working-memory impairment characteristic of animal models of chronic pain is dependent on hippocampal dopaminergic signaling. To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 region of rats and recorded the neuronal activity during a food-reinforced spatial WM task of trajectory alternation. Within-subject behavioral performance and patterns of dorsoventral neuronal activity were assessed before and after the onset of persistent neuropathic pain using the Spared Nerve Injury (SNI) model of neuropathic pain. Our results show that the peripheral nerve lesion caused a disruption in WM and in hippocampus spike activity and that this disruption was reversed by the systemic administration of the dopamine D2/D3 receptor agonist quinpirole (0.05 mg/kg). In SNI animals, the administration of quinpirole restored both the performance-related and the task-related spike activity to the normal range characteristic of naive animals, whereas quinpirole in sham animals caused the opposite effect. Quinpirole also reversed the abnormally low levels of hippocampus dorsoventral connectivity and phase coherence. Together with our finding of changes in gene expression of dopamine receptors and modulators after the onset of the nerve injury model, these results suggest that disruption of the dopaminergic balance in the hippocampus may be crucial for the clinical neurological and cognitive deficits observed in patients with painful syndromes.


Endocrinopathies in Turkish children with Beta thalassemia major: results from a single center study.
The endocrinological complications in β-thalassemia major patients do affect the life quality to a large extend. In this study, the endocrinological complications of 47 β-thalassemia patients, who have been followed-up at our hospital's pediatric hematology department, were evaluated. Out of β-thalassemia major cases included to this study, the 55.3% was male and 44.7% was female. The patients' mean levels of ferritin, whose mean age was 10.0 ± 4.5 years (2-20 years), were 2497 ± 1469 ng/mL (472-8558 ng/mL). At least one endocrinological pathology in 27 out of 47 (57.4%) and more than one endocrinological pathology in 14 out of 47 (29.7%) thalassemia patients were observed. The most frequently observed complication in followed-up cases was vitamin D insufficiency and deficiency (78.2%). The other complications in decreasing order were pubertal failure (41.6%), growth retardation (25.5%), decreased bone-mineral density (22.2%), secondary hyperparathyroidism (11.5%), overt hypothyroidism (4.25%), subclinical hypothyroidism (2.12%), and impaired glucose tolerance (2.12%). There was no statistically significant difference between serum mean ferritin level and endocrin complications (P > .05). Four patients (8.5%) had decreased signal intensity in pituitary magnetic resonance imaging (MRI) but this finding was not associated with ferritin levels (P = .87). MRI parameters were similar between patients with and without gonadal dysfunction. Mean height of the pituitary gland was 4.98 ± 1.1 mm (3-9 mm) and this was similar to those normal values in the literature. Ferritin levels were not correlated with pituitary height (P > .05). Beta thalassemia major, having the potential of leading to multisystemic complications, is a chronic disease that should be treated and followed-up by a multidisciplinary approach. Due to frequently encountered endocrinological complications, beta thalassemic patients should be followed-up regularly by hematology and endocrinology departments in coordination.


THE DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES. MORPHOLOGY, CYTOCHEMISTRY, AND BIOCHEMISTRY.
The in vitro differentiation of homogeneous populations of monocyte-like cells from the unstimulated mouse peritoneal cavity is described. Under the conditions employed, a progressive increase in cell size occurs without significant cell division. This process is characterized morphologically by the accumulation of phase-dense and neutral red-positive granules, mitochondria, and lipid droplets. The phase-dense granules react strongly for acid phosphatase. Biochemical determinations indicate marked increases in the total content and specific activity of acid phosphatase, cathepsin, and beta-glucuronidase. The production of acid phosphatase is more rapid and extensive than that of the other two hydrolases. From these data it appears that the conversion of a monocyte-like cell to a mature macrophage is accompanied by the formation of increased numbers of lysosome-like cytoplasmic organelles. Mouse peritoneal phagocytes stimulated in vivo with a bacterial lipopolysaccharide undergo a similar series of morphological and biochemical events.


How good are the numbers for cigarette tar at predicting deliveries of carbon monoxide, hydrogen cyanide, and acrolein?
Simple and multiple linear regression analyses were performed on the tar, nicotine, CO, HCN, and acrolein deliveries of 98 brands of commercially available Canadian cigarettes. Simple linear regressions of CO, HCN, and acrolein on tar and of acrolein on CO were not significant at the 5% level for plain cigarettes; all other regressions were very strongly significant (p less than 0.01). In addition there was strong statistical evidence that filter, vented filter, and plain cigarettes have different regression relations and different levels of precision associated with the regression parameters. With respect to CO, tar level could predict the corresponding CO value only within 3.9 mg (filter), 1.9 mg (vented filter), and 3.1 mg (plain). These results show that tar delivery alone is an inadequate predictor of gas-phase constituents such as CO. Information concerning these constituents is best conveyed by an analytically determined value for each component.


The Neuroimaging Spectrum of Septum Posticum Derangement and Associated Thoracic Myelopathy.
Arachnoid cysts and meningeal membranes are among the differential diagnostic considerations of extra-medullary causes of thoracic myelopathy. In this case series of 7 patients, we present compressive meningeal membranes mimicking dorsal arachnoid cyst. The propensity of the meningeal membranes for the dorsal aspect of upper thoracic spine may reflect derangements of the septum posticum. To provide the spectrum of imaging appearances and clinical presentations of pathology of the septum posticum to improve imaging utilization and to better guide treatment planning. Seven patients aged 40 to 75 with MRI findings of ventral displacement and dorsal cord compression in the upper thoracic spine were further evaluated with CT-myelograms. The primary indication was to exclude dorsal arachnoid cyst. Two patients with progressive symptoms and lower extremity weakness were operated for decompression. CT-myelogram excluded space occupying lesions and cord herniation in all cases. Intradural dorsal meningeal webs and membranes were inconsistently visualized. In the 2 operated cases, thick coalescing membranes and hyperdynamic turbulent CSF flow were severely compressing the thoracic cord. Derangements of septum posticum may present a spectrum of findings that should be considered in the differential of thoracic myelopathy. Flattening of the posterior cord margin is a reliable imaging clue for a dorsal extra-medullary compressive lesion. Cord compression results from combination of adhesive membranes and turbulent CSF flow. The clinical course may be difficult to predict. Periodic imaging follow up can be helpful to confirm stability of findings in expectantly managed cases.


Effect of 6% Hydroxyethyl Starch 130/0.4 on Inflammatory Response and Pulmonary Function in Patients Having Cardiac Surgery: A Randomized Clinical Trial.
Cardiac surgery with cardiopulmonary bypass induces a profound inflammatory response that, when severe, can lead to multiorgan system dysfunction. Preliminary data suggest that administration of hydroxyethyl starch (HES) solutions may mitigate an inflammatory response and improve pulmonary function. Our goal was to examine the effect of 6% HES 130/0.4 versus 5% human albumin given for intravascular plasma volume replacement on the perioperative inflammatory response and pulmonary function in patients undergoing cardiac surgery. This was a subinvestigation of a blinded, parallel-group, randomized clinical trial of patients undergoing elective aortic valve replacement surgery at the Cleveland Clinic main campus, titled "Effect of 6% Hydroxyethyl Starch 130/0.4 on Kidney and Haemostatic Function in Cardiac Surgical Patients." Of 141 patients who were randomized to receive either 6% HES 130/0.4 or 5% human albumin for intraoperative plasma volume replacement, 135 patients were included in the data analysis (HES n = 66, albumin n = 69). We assessed the cardiopulmonary bypass-induced inflammatory response end points by comparing the 2 groups' serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and macrophage migration inhibitory factor (MIF), measured at baseline and at 1 and 24 hours after surgery. We also compared the 2 groups' postoperative pulmonary function end points, including the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen (Pao2:Fio2 ratio), dynamic lung compliance, oxygenation index (OI), and ventilation index (VI) at baseline, within 1 hour of arrival to the intensive care unit, and before tracheal extubation. The differences in the postoperative levels of inflammatory response and pulmonary function between the HES and albumin groups were assessed individually in linear mixed models. Serum concentrations of the inflammatory markers (TNF-α, IL-6, MIF) were not significantly different (P ≥ .05) between patients who received 6% HES 130/0.4 or 5% albumin, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). The results of pulmonary function parameters (Pao2:Fio2 ratio, dynamic compliance, OI, VI) were not significantly different (P ≥ .05) between groups, and there was no significant heterogeneity of the estimated treatment effect over time (P ≥ .15). Our investigation found no significant difference in the concentrations of inflammatory markers and measures of pulmonary function between cardiac surgical patients who received 6% HES 130/0.4 versus 5% albumin.


Talking therapy: The allopathic nihilation of homoeopathy through conceptual translation and a new medical language.
The 19th century saw the development of an eclectic medical marketplace in both the United Kingdom and the United States, with mesmerists, herbalists and hydrotherapists amongst the plethora of medical 'sectarians' offering mainstream (or 'allopathic') medicine stiff competition. Foremost amongst these competitors were homoeopaths, a group of practitioners who followed Samuel Hahnemann (1982[1810]) in prescribing highly dilute doses of single-drug substances at infrequent intervals according to the 'law of similars' (like cures like). The theoretical sophistication of homoeopathy, compared to other medical sectarian systems, alongside its institutional growth after the mid-19th-century cholera epidemics, led to homoeopathy presenting a challenge to allopathy that the latter could not ignore. Whilst the subsequent decline of homoeopathy at the beginning of the 20th century was the result of multiple factors, including developments within medical education, the Progressive movement, and wider socio-economic changes, this article focuses on allopathy's response to homoeopathy's conceptual challenge. Using the theoretical framework of Berger and Luckmann (1991[1966]) and taking a Tory historiographical approach (Fuller, 2002) to recover more fully 19th-century homoeopathic knowledge, this article demonstrates how increasingly sophisticated 'nihilative' strategies were ultimately successful in neutralising homoeopathy and that homoeopaths were defeated by allopaths (rather than disproven) at the conceptual level. In this process, the therapeutic use of 'nosodes' (live disease products) and the language of bacteriology were pivotal. For their part, homoeopaths failed to mount a counter-attack against allopaths with an explanatory framework available to them.


Profile of JTE-522 as a human cyclooxygenase-2 inhibitor.
Inhibitory activity and the mechanism of action of JTE-522 (4-(4-cyclohexyl-2-methyloxazol-5-yl)-2-fluorobenzenesulfonamid e), a novel selective cyclooxygenase (COX)-2 inhibitor, on human COX-1 and COX-2 were investigated and compared with those of reference compounds. In an enzyme assay, JTE-522 inhibited yeast-expressed human recombinant COX-2 with an IC50 value of 0.085 microM. In contrast, JTE-522 did not inhibit human COX-1 prepared from human platelets at concentrations up to 100 microM. In a cell-based assay, JTE-522 diminished lipopolysaccharide-induced prostaglandin E2 production in human peripheral blood mononuclear cells (COX-2) (IC50 value = 15.1 nM). On the other hand, JTE-522 was less potent at inhibiting calcium ionophore-induced thromboxane B2 production in washed human platelets (COX-1) (IC50 value = 6210 nM). JTE-522 showed highly selective inhibition of human COX-2, and its activity was more selective than that of other COX-2 inhibitors (NS-398 and SC-58635). Human recombinant COX-2 activity was attenuated by JTE-522 in a dose-dependent and time-dependent manner. In contrast, the inhibitory activity of JTE-522 on human COX-1 was not affected by preincubation time. COX-2 inhibition by JTE-522 could not be recovered by gel filtration. These results indicate that JTE-522 is a highly selective, time-dependent and irreversible inhibitor of human COX-2.


Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats.
Recent anatomical evidence suggests that the shell of the nucleus accumbens, the bed nucleus of the stria terminalis, and the central nucleus of the amygdala, together referred to as the extended amygdala, may play a role in opiate dependence. The bed nucleus of the stria terminalis and the shell of the nucleus accumbens have a moderately high density of opiate receptors, which allows for manipulation of opiate neurotransmission with receptor antagonists. The goal of this study was to determine the role these regions play in opiate reinforcement, and whether dependence alters the reinforcing effects of opiates by examining the effect of local administration of the opiate receptor antagonist methylnaloxonium on heroin self-administration in dependent and nondependent rats. Previous studies revealed that blockade of the reinforcing effects of opiates with systemic administration of opiate receptor antagonists results in an increase in heroin self-administration in nondependent rats, and a greater increase in dependent rats. In the present study, methylnaloxonium dose-dependently suppressed heroin intake when injected into the bed nucleus of the stria terminalis and shell of the nucleus accumbens of dependent rats, and had no effect in nondependent rats. These results demonstrate that opiate receptors in parts of the extended amygdala may be responsible for the reinforcing effects of opiates in dependent animals and suggest that activity in this system may be recruited during the development of dependence.


Connective tissue synthesis by scleroderma skin fibroblasts in cell culture.
Skin fibroblasts from subjects with scleroderma and control subjects were grown in tissue culture to compare the characteristics of connective tissue metabolism. A striking increase in soluble collagen (media hydroxyproline) was observed in eight of nine scleroderma cultures when they were compared with identically handled control cultures matched for the age and sex of the donor and the anatomic site of the donor skin. Glycoprotein content as estimated by hexosamine and sialic acid was also significantly increased in the scleroderma cultures. Estimations of protein-polysaccharide content by uronic acid determinations were low in all cultures and not significantly increased in scleroderma cultures. This report demonstrates the feasibility of using fibroblast cell cultures to study chronic rheumatic and connective tissue disorders. The initial results suggest a net increase in collagen and glycoprotein synthesis in scleroderma fibroblast cultures. The implications of an abnormality of connective tissue metabolism by skin fibroblasts propagated in vitro in the acquired disorder scleroderma are discussed.


Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development.
Premature breast development (thelarche) is the growth of mammary tissue in girls younger than 8 years of age without other manifestations of puberty. Puerto Rico has the highest known incidence of premature thelarche ever reported. In the last two decades since this serious public health anomaly has been observed, no explanation for this phenomenon has been found. Some organic pollutants, including pesticides and some plasticizers, can disrupt normal sexual development in wildlife, and many of these have been widely used in Puerto Rico. This investigation was designed to identify pollutants in the serum of Puerto Rican girls with premature thelarche. A method for blood serum analysis was optimized and validated using pesticides and phthalate esters as model compounds of endocrine-disrupting chemicals. Recovery was > 80% for all compounds. We performed final detection by gas chromatography/mass spectrometry. We analyzed 41 serum samples from thelarche patients and 35 control samples. No pesticides or their metabolite residues were detected in the serum of the study or control subjects. Significantly high levels of phthalates [dimethyl, diethyl, dibutyl, and di-(2-ethylhexyl)] and its major metabolite mono-(2-ethylhexyl) phthalate were identified in 28 (68%) samples from thelarche patients. Of the control samples analyzed, only one showed significant levels of di-isooctyl phthalate. The phthalates that we identified have been classified as endocrine disruptors. This study suggests a possible association between plasticizers with known estrogenic and antiandrogenic activity and the cause of premature breast development in a human female population.


Explaining educational inequalities in preterm birth: the generation r study.
Although a low socioeconomic status has consistently been associated with an increased risk of preterm birth, little is known about the pathways through which socioeconomic disadvantage influences preterm birth. To examine mechanisms that might underlie the association between the educational level of pregnant women as an indicator of socioeconomic status, and preterm birth. The study was nested in a population-based cohort study in the Netherlands. Information was available for 3830 pregnant women of Dutch origin. The lowest-educated pregnant women had a statistically significant higher risk of preterm birth (odds ratio (OR) = 1.89 (95% CI 1.28 to 2.80)) than the highest educated women. This increased OR was reduced by up to 22% after separate adjustment for age, height, preeclampsia, intrauterine growth restriction, financial concerns, long-lasting difficulties, psychopathology, smoking habits, alcohol consumption, and body mass index (BMI) of the pregnant women. Joint adjustment for these variables resulted in a reduction of 89% of the increased risk of preterm birth among low-educated pregnant women (fully adjusted OR = 1.10 (95% CI 0.66 to 1.84)). Pregnant women with a low educational level have a nearly twofold higher risk of preterm birth than women with a high educational level. This elevated risk could largely be explained by pregnancy characteristics, indicators of psychosocial well-being, and lifestyle habits. Apparently, educational inequalities in preterm birth go together with an accumulation of multiple adverse circumstances among women with a low education. A number of explanatory mechanisms unravelled in the present study seem to be modifiable by intervention programmes.


Can we predict urinary stone composition based on an analysis of microelement concentration in the hair and urine?
In recent years the role of trace elements in lithogenesis has received steadily increasing attention. This study was aimed to attempt to find the correlations between the chemical content of the stones and the concentration of chosen elements in the urine and hair of stone formers. The proposal for the study was approved by the local ethics committee. Specimens were taken from 219 consecutive stone-formers. The content of the stone was evaluated using atomic absorption spectrometry, spectrophotometry, and colorimetric methods. An analysis of 29 elements in hair and 21 elements in urine was performed using inductively coupled plasma-atomic emission spectrometry. Only a few correlations between the composition of stones and the distribution of elements in urine and in hair were found. All were considered incidental. The data obtained did not allow for the creation of a proper and practical algorithm to predict stone chemical composition based on hair and urine analysis.


Transfer Learning With Singular Value Decomposition of Multichannel Convolution Matrices.
The task of transfer learning using pretrained convolutional neural networks is considered. We propose a convolution-SVD layer to analyze the convolution operators with a singular value decomposition computed in the Fourier domain. Singular vectors extracted from the source domain are transferred to the target domain, whereas the singular values are fine-tuned with a target data set. In this way, dimension reduction is achieved to avoid overfitting, while some flexibility to fine-tune the convolution kernels is maintained. We extend an existing convolution kernel reconstruction algorithm to allow for a reconstruction from an arbitrary set of learned singular values. A generalization bound for a single convolution-SVD layer is devised to show the consistency between training and testing errors. We further introduce a notion of transfer learning gap. We prove that the testing error for a single convolution-SVD layer is bounded in terms of the gap, which motivates us to develop a regularization model with the gap as the regularizer. Numerical experiments are conducted to demonstrate the superiority of the proposed model in solving classification problems and the influence of various parameters. In particular, the regularization is shown to yield a significantly higher prediction accuracy.


Drinking water while fracking: now and in the future.
The data provided by the PA DEP are incomplete because confidential data are not released. It is impossible to make firm conclusions about water quality impacts when data availability is limited. Nonetheless, the PA experience appears to be characterized by a low rate of problems per gas well or unit of gas produced. Only about 160 of the complaints from homeowners about groundwater to the PA DEP between 2008 and 2012 were problems attributed to oil and gas activity—and only half of these were caused by companies known to drill unconventional shale wells. These problematic wells in turn represent only 0.1 to 1% of the unconventional shale gas wells drilled in that time period (Brantley et al. 2014). Management practices appear to be improving as well; the rate of problems has decreased since 2010 (Figure 1). Apparently, however, the public responds not only to the number of problems per gas well or per unit of gas produced but rather to the number of problems per unit time and per unit area. Thus, even though the r ate of problems with shale gas wells has remained small on a per well basis, pushback has grown in areas of increasing density of drilling and fracking. This may be especially true when consequences are fearsome such as flaming tapwater, toxic contamination, or earthquakes. It is natural that the social license for shale gas development is influenced by short-term, local thinking. But, such thinking may not be helpful given that Marcellus Shale gas wells generate one third the waste per unit volume of gas as compared to conventional shallow gas wells (Vidic et al. 2013). In addition, the release of pollutants such as carbon dioxide, particulates, mercury, nitrogen, and sulfur generated per unit of heat energy is lower f or unconventional shale gas than for fuels such as coal (Heath et al. 2014). Public pushback could nonetheless be a blessing. After all, pushback represents intensified interest in environmental issues. This interest may be seen in the PA DEP data for the rate of well integrity issues in conventional oil and gas wells—the increase in problem rate from 2008 to 2012 (Figure 1) is more likely due to heightened public attention and inspector scrutiny rather than a sudden deterioration in the management practices of the drilling companies (Brantley et al. 2014) During the next decades, the rate of hydraulic fracturing in PA will eventually slow. At some point, the use of produced brines to hydrofracture new wells will cease. Once recycling of brine to frack new wells stops, hundreds of gallons of brine will accumulate as waste at each well per day (Rahm et al. 2013). Disposal of this slightly radioactive brine will then become increasingly problematic. Interest on the part of the public for such issues is warranted. Public engagement today is needed to develop sustainable waste management and sustainable energy practices for the future.


Treatment staff's continuity of care practices, patients' engagement in continuing care, and abstinence following outpatient substance-use disorder treatment.
Although speculation suggests that continuity of care predicts abstinence following substance-use disorder (SUD) treatment, models examining staff's continuity of care practices and engagement in continuing care and whether they mediate or moderate the association between patient and treatment factors and abstinence are lacking. In this study, we aimed to model abstinence using combinations of independent pretreatment and treatment factors, discharge continuity of care practices, and posttreatment engagement and to identify mediators or moderators of relationships between these factors and abstinence. Staff in 18 Department of Veterans Affairs (VA) outpatient SUD programs used the Addiction Severity Index to assess 429 nonabstinent patients' alcohol and drug problems at treatment entry. Staff supplied discharge data on patients' motivation, treatment intensity and completion, and continuity of care practices. Administrative data assessed patients' continuing care engagement. A 6-month follow-up, the Addiction Severity Index assessed abstinence. Mixed-effects logistic regression models were used to examine predictors of abstinence. Abstinence occurred more when discharge plans specified at least one continuing care appointment per week, patients received continuing care appointments before discharge, and staff provided patients drug-free/sober living arrangements and with longer engagement in continuing care. SUD/psychiatric clinic use before treatment entry, treatment completion, access to transportation for continuing care appointments, and more patient motivation for continuing care also predicted abstinence. Engagement in continuing care mediated the relationship between continuity of care and abstinence and between SUD/psychiatric clinic use and abstinence. Findings suggest that continuity of care practices influence abstinence mostly through their effect on patients' engagement in continuing care.


[Nitrogen dioxide]
In order to assess level of human exposure to nitrogen dioxide, 22 traffic police from the city of Rio de Janeiro were monitored during their working hours for 3 consecutive days. Samples were taken by using a passive sampler (badge) and analyzed spectrophotometrically after reacting with sulphanilic acid followed by coupling with N-naphtilethylenediamine dihydrochloride. Results ranged from 13.3 to 193.6 mg/m3. According to the literature, these levels are not associated with any acute damage to human health but care should be taken to avoid long-term problems.


Incidence of hemorrhagic stroke in the general population: validation of data from The Health Improvement Network.
The Health Improvement Network (THIN) is a UK healthcare database composed of computerized information from primary care physicians (PCPs). We analyzed the validity of our method for identifying cases of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) within THIN and assessed the incidence of these events. Patients aged 20-89 years were identified and followed until (i) ICH or SAH was detected, (ii) the patient reached 90 years old (iii) death, or (iv) the end of the study. Computerized patient profiles were reviewed manually; those not discarded became potential cases. A validation study was undertaken in 400 computer-detected cases (333 confirmed as potential cases; 67 discarded). PCPs completed a questionnaire to determine the actual incidence of ICH and SAH among these cases. We also assessed the incidence of ICH and SAH in the total cohort. A total of 4330 patients with a READ code suggesting hemorrhagic stroke were identified. Computerized profiles with free-text comments were reviewed manually to identify 3633 potential cases. Responses to the PCP questionnaire were received for 306 potential cases and 63 discarded cases (92% response rate); 82% of potential cases were confirmed. Finally, we identified 3137 cases of hemorrhagic stroke. Crude incidence was 15 per 100,000 person-years for ICH and 11 per 100,000 person-years for SAH; the overall incidence increased sharply with age. Computer detection of cases of hemorrhagic stroke in THIN followed by manual review of clinical profiles is a valid method. The incidence of hemorrhagic stroke increases sharply with age.


[Dietary fibers in diet therapy].
Dietary fibers belong to the group of polymeric compounds with different chemical origin. They play an important part in functioning of number of organs and body systems and in the first place influence upon the function of large intestine. Having ability to retain water, they accelerate an intestine transit and peristalsis of large intestine, and are the stool forming factor. Dietary fibers adsorb many bile acids, metabolites, toxins and electrolytes and promote detoxification of organism. Due to ionchange properties dietary fibers are capable to remove ions of heavy metals and radionuclides. Dietary fibers render positive action during the functional diseases of large intestine, reduce blood cholesterol concentration, have hypolipidemic effect and can be used for prophylactic and therapy of cardiovascular and other diseases.


Childhood remembered: Reports of both unique and repeated events.
To explore the significance of repeated memories for individuals' personal histories, we compared the characteristics of young adults' unique and repeated memories of childhood experiences. Memory type (unique vs. repeated) was a within-participant variable. In Experiment 1, college-age participants generated as many early memories as possible in 4 minutes; in Experiment 2, another sample provided complete reports of five early memories in each condition. In both experiments, participants rated the vividness, biographical importance and personal meaning of each memory and labelled the accompanying emotion. Unique memories were more vivid than repeated memories as well as more likely to include negative emotion, regardless of the method of reporting. Most importantly, college students rated their memories for unique and repeated events as equivalently infused with personal meaning. Analysis of the content of the memories reported in Experiment 2 established that unique and repeated memories did not differ in word count or percentages of perceptual terms or words indicating positive affect, although unique memories contained a greater percentage of negative affect. Additional analyses of content provided evidence for differences in the functions served by unique and repeated memories. The results have implications for the study of autobiographical memory and for identifying over-general memories.


Enhanced cell volume regulation: a key mechanism in local and remote ischemic preconditioning.
We have previously shown that ischemic preconditioning (IPC) protection against necrosis in whole hearts and in both fresh and cultured cardiomyocytes, as well as the improved regulatory volume decrease to hypoosmotic swelling in cardiomyocytes, is abrogated through Cl(-) channel blockade, pointing to a role for enhanced cell volume regulation in IPC. To further define this cardioprotective mechanism, cultured rabbit ventricular cardiomyocytes were preconditioned either by 10-min simulated ischemia (SI) followed by 10-min simulated reperfusion (SR), by 10-min exposure/10-min washout of remote IPC (rIPC) plasma dialysate (from rabbits subjected to repetitive limb ischemia), or by adenoviral transfection with the constitutively active PKC-ε gene. These interventions were done before cardiomyocytes were subjected to either 60- or 75-min SI/60-min SR to assess cell necrosis (by trypan blue staining), 30-min SI to assess ischemic cell swelling, or 30-min hypoosmotic (200 mosM) stress to assess cell volume regulation. Necrosis after SI/SR and both SI- and hypoosmotic stress-induced swelling was reduced in preconditioned cardiomyocytes compared with control cardiomyocytes (neither preconditioned nor transfected). These effects on necrosis and cell swelling were blocked by either Cl(-) channel blockade or dominant negative knockdown of inwardly rectifying K(+) channels with adenoviruses, suggesting that Cl(-) and K(+) movements across the sarcolemma are critical for cell volume regulation and, thereby, cell survival under hypoxic/ischemic conditions. Our results define enhanced cell volume regulation as a key common mechanism of cardioprotection by preconditioning in cardiomyocytes.


Use of the amniotic fluid index combined with estimated fetal weight within 10 days of delivery for prediction of macrosomia at birth.
The purpose of this study was to assess the value of combining the sonographically estimated fetal weight (EFW) and amniotic fluid index (AFI) measured within 10 days of term delivery for prediction of macrosomia at birth. Prospective sonographic fetal biometric measurements and delivery ward data of a single center, uploaded separately over a 4-year period, were retrospectively linked to yield an unselected sample of nondiabetic pregnancies with live-born term neonates. Of the 1925 pregnancies evaluated, 140 (7.2%) were macrosomic (birth weight > or =4000 g). The AFI was significantly higher in the macrosomic group (P < .001). On receiver operating characteristic curve analysis, the area under the curve was larger for predictions based on the EFW alone than on the AFI. An EFW of 4000 g or higher had a positive predictive value of 46.6% for macrosomia at birth. Use of the previously suggested combined EFW and AFI cutoffs of 3689 g and 119 mm, respectively, yielded a positive predictive value of 30.3%. Combined use of the EFW and AFI rather than the EFW alone does not improve prediction of macrosomia at birth.


A Varying Role for Abstraction in Models of Category Learning Constructed from Neural Representations in Early Visual Cortex.
The human capacity for visual categorization is core to how we make sense of the visible world. Although a substantive body of research in cognitive neuroscience has localized this capacity to regions of human visual cortex, relatively few studies have investigated the role of abstraction in how representations for novel object categories are constructed from the neural representation of stimulus dimensions. Using human fMRI coupled with formal modeling of observer behavior, we assess a wide range of categorization models that vary in their level of abstraction from collections of subprototypes to representations of individual exemplars. The category learning tasks range from simple linear and unidimensional category rules to complex crisscross rules that require a nonlinear combination of multiple dimensions. We show that models based on neural responses in primary visual cortex favor a variable, but often limited, extent of abstraction in the construction of representations for novel categories, which differ in degree across tasks and individuals.


iWRAP: A Theranostic Wearable Device With Real-Time Vital Monitoring and Auto-Adjustable Compression Level for Venous Thromboembolism.
Venous Thromboembolism (VTE) is a commonly underdiagnosed disease with severe consequences and an exceedingly high mortality rate. Conventional compression wraps are devised for therapeutic purpose but lack diagnostic capacity. Recent advances in flexible electronics and wearable technologies offer many possibilities for chronic disease management. In particular, vital signs have been studied to show a strong correlation with the risk of VTE patients. In this study, we aim to develop an intelligent theranostic compression device, referred to as iWRAP, with the built-in capacity of real-time vital sign monitoring together with auto-adjustable compression level. An instantaneous pneumatic feedback control with a high-resolution pressure sensor is integrated to provide a highly stabilized compression level at the prescribed interface pressure for an improved therapeutic outcome. Meanwhile, arterial pulse waveforms extracted from the pressure readings from the smart compression device can be utilized to derive the body vital signs, including heart rate (HR), respiratory rate (RR) and blood pressure (BP). A reliable delivery of the targeted compression level within ±5% accuracy in the range of 20-60 mmHg has been achieved through the feedback of the interface pressure. Both HR and RR have been measured within clinical-grade accuracies. Moreover, BP estimated using an ALA model has been achieved at low compression levels, which is also within a clinical-acceptable accuracy. The acquired vital information has been instantaneously fit into the clinically acceptable criteria for life-threatening PE risk with timely assessments. The iWRAP has shown the potential to become the first theranostic wearable device with both continuous delivery of accurate and effective compression therapy and real-time monitoring of life-threatening conditions for VTE patients.


Platelet glycoprotein IIb/IIIa receptor blockade in coronary artery disease.
New strategies for profound inhibition of platelet activity at the injured coronary plaque focus on blockade of the platelet surface membrane glycoprotein IIb/IIIa receptor, which binds circulating fibrinogen or von Willebrand factor and crosslinks platelets as the final common pathway to platelet aggregation. Intravenous agents directed against this receptor include the chimeric monoclonal antibody fragment abciximab, the peptide inhibitor eptifibatide and nonpeptide mimetics tirofiban and lamifiban. Over 33,000 patients have been evaluated in 11 large-scale, placebo-controlled trials of these agents. During percutaneous coronary intervention, an absolute reduction of 1.5% to 6.5% in the 30-day risk of death, myocardial infarction or repeat urgent revascularization has been observed, with some variability in treatment effect among the agents tested (abciximab, eptifibatide and tirofiban). Treatment effect is achieved early with every modality of revascularization and is maintained over the long-term (up to three years). Increased bleeding risk may be minimized by reduction and weight-adjustment of concomitant heparin dosing. In the acute coronary syndromes without ST segment elevation, absolute 1.5% to 3.2% reductions in 30-day rates of death or myocardial (re-) infarction have been achieved with two to four day courses of eptifibatide or tirofiban. Clinical benefit accrues during the period of drug infusion and is durable. Treatment effect may be enhanced among patients undergoing early coronary revascularization, with evidence of stabilization before intervention and suppression of postprocedural ischemic events. Thus, blockade of the platelet glycoprotein IIb/IIIa receptor reduces ischemic complications when used as an adjunct to percutaneous coronary intervention or the management of acute ischemic syndromes.