Low-carbohydrate diets.
Americans spend dollar 33 billion annually on weight loss products and services, and a large portion of this money is spent on low-carbohydrate diets. Because of their higher protein and fat content and lower fiber and carbohydrate content, concerns have been raised about the potential health consequences of low-carbohydrate diets. Published long-term data are lacking. Short-term studies comparing traditional low-fat diets with low-carbohydrate diets found lower triglyceride levels, higher high-density lipoprotein cholesterol levels, similar low-density lipoprotein cholesterol levels, and lower A1C levels in persons on low-carbohydrate diets. These diets induce greater weight loss at three and six months than traditional low-fat diets; however, by one year there is no significant difference in maintained weight loss. Weight loss is directly related to calorie content and the ability to maintain caloric restriction; the proportions of nutrients in the diet are irrelevant. Low-carbohydrate diets had lower dropout rates than low-fat diets in several studies, possibly because of the high protein content and low glycemic index, which can be appetite suppressing. Data indicate that low-carbohydrate diets are a safe, reasonable alternative to low-fat diets for weight loss. Additional studies are needed to investigate the long-term safety and effectiveness of these and other approaches to weight loss.


Extended analysis of a genome-wide association study in primary sclerosing cholangitis detects multiple novel risk loci.
A limited number of genetic risk factors have been reported in primary sclerosing cholangitis (PSC). To discover further genetic susceptibility factors for PSC, we followed up on a second tier of single nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS). We analyzed 45 SNPs in 1221 PSC cases and 3508 controls. The association results from the replication analysis and the original GWAS (715 PSC cases and 2962 controls) were combined in a meta-analysis comprising 1936 PSC cases and 6470 controls. We performed an analysis of bile microbial community composition in 39 PSC patients by 16S rRNA sequencing. Seventeen SNPs representing 12 distinct genetic loci achieved nominal significance (p(replication) <0.05) in the replication. The most robust novel association was detected at chromosome 1p36 (rs3748816; p(combined)=2.1 × 10(-8)) where the MMEL1 and TNFRSF14 genes represent potential disease genes. Eight additional novel loci showed suggestive evidence of association (p(repl) <0.05). FUT2 at chromosome 19q13 (rs602662; p(comb)=1.9 × 10(-6), rs281377; p(comb)=2.1 × 10(-6) and rs601338; p(comb)=2.7 × 10(-6)) is notable due to its implication in altered susceptibility to infectious agents. We found that FUT2 secretor status and genotype defined by rs601338 significantly influence biliary microbial community composition in PSC patients. We identify multiple new PSC risk loci by extended analysis of a PSC GWAS. FUT2 genotype needs to be taken into account when assessing the influence of microbiota on biliary pathology in PSC.


Could sterile males be used to vector a microbiological control agent? The case of Rhynchophorus ferrugineus and Beauveria bassiana.
Rhynchophorus ferrugineus (Coleoptera, Curculionidae) is the most threatening pest of palms worldwide. The potential of gamma-irradiated males to spread a pathogenic strain of the entomopathogenic fungus Beauveria bassiana (Ascomycota: Clavicipitaceae) to control this pest was studied. First, the effects of gamma irradiation (15 and 25 Gy) on the mating success and performance of adult males irradiated at age one day were studied in the laboratory. Although male longevity decreased after irradiation (118.6 vs. 244.7 days for irradiated and control males, respectively) and their testes suffered from the treatment, fecundity of mated females did not depend on the irradiation status of the male (86.8 ± 5.5 eggs in 15 days). However, egg hatching was significantly lower in couples with irradiated males (31.4% vs. 86.5% for irradiated and control couples, respectively), and this value decreased after a second mating (6.1% vs. 85.9%). Therefore, irradiation did not affect male sexual competiveness but sperm quality. Second, a semi-field assay was carried out to evaluate infestation in young Phoenix canariensis caused by different combinations of couples with irradiated and/or B. bassiana-challenged males. The number of immature stages found in infested palms was significantly higher when females mated with untreated males and lower when mated with irradiated males (either B. bassiana-infected or not). Some females from the fungus-challenged treatments showed post-mortem hyphal growth, and this horizontal transmission proves that irradiated males could act as a vector for B. bassiana and should be considered as a new method to improve the biological control of R. ferrugineus.


Electronic algorithmic prediction of central vascular catheter use.
To develop prediction algorithms for the presence of a central vascular catheter in hospitalized patients with use of data present in an electronic health record. Such algorithms could be used for measurement of device utilization rates and for clinical decision support rules. Criterion standard. John H. Stroger, Jr, Hospital of Cook County, a 464-bed public hospital in Chicago, Illinois. Patients admitted to the medical intensive care unit from May 31, 2005 through June 26, 2006 (derivation data set, May 31, 2005-September 28, 2005; validation data set, September 29, 2005-June 28, 2006). Covariates were collected from the electronic medical record for each patient; the outcome variable was presence of a central vascular device. Multivariate models were developed using the derivation set and the generalized estimating equation. Three models, each with increasing database requirements, were validated using the validation set. Device utilization ratios and performance characteristics were calculated. Although Charlson score and duration of intensive care unit stay were significant predictors in all models, factors that indicated use or presence of a central line were also important. Device utilization rates derived from the algorithmic models were as accurate as those obtained using manual sampling. Automated calculation of central vascular catheter use is both feasible and accurate, providing estimates statistically similar to those obtained using manual surveillance. Prediction modeling of central vascular catheter use may enable automated surveillance of bloodstream infections and enhance important prevention interventions, such as timely removal of unnecessary central lines.


Maternal Vitamin D Status and the Relationship with Neonatal Anthropometric and Childhood Neurodevelopmental Outcomes: Results from the Seychelles Child Development Nutrition Study.
Vitamin D has an important role in early life; however, the optimal vitamin D status during pregnancy is currently unclear. There have been recent calls for pregnant women to maintain circulating 25-hydroxyvitamin D (25(OH)D) concentrations >100 nmol/L for health, yet little is known about the long-term potential benefits or safety of achieving such high maternal 25(OH)D concentrations for infant or child health outcomes. We examined maternal vitamin D status and its associations with infant anthropometric and later childhood neurocognitive outcomes in a mother-child cohort in a sun-rich country near the equator (4.6° S). This study was conducted in pregnant mothers originally recruited to the Seychelles Child Development Nutrition Study. Blood samples (n = 202) taken at delivery were analysed for serum 25-hydroxyvitamin D (25(OH)D) concentrations. Multiple linear regression models assessed associations between maternal 25(OH)D and birth weight, infant head circumference, and neurocognitive outcomes in the children at age 5 years. Mothers were, on average, 27 years of age, and the children's average gestational age was 39 weeks. None of the women reported any intake of vitamin D supplements. Maternal 25(OH)D concentrations had a mean of 101 (range 34-218 nmol/L) and none were deficient (<30 nmol/L). Maternal 25(OH)D concentrations were not associated with child anthropometric or neurodevelopmental outcomes. These findings appear to indicate that a higher vitamin D status is not a limiting factor for neonatal growth or neurocognitive development in the first 5 years of life. Larger studies with greater variability in vitamin D status are needed to further explore optimal cut-offs or non-linear associations (including for maternal health) that might exist among populations with sub-optimal exposure.


Podocalyxin-like protein expression in primary colorectal cancer and synchronous lymph node metastases.
Previous studies have shown that membranous expression of podocalyxin-like protein (PODXL) is associated with poor prognosis in colorectal cancer (CRC). In this study, we compared PODXL expression in primary CRC and synchronous lymph node metastases. We further analyzed whether its expression changed in rectal tumours after neoadjuvant radiation therapy. The studied cohort consists of 73 consecutive patients from the South-Swedish Colorectal Cancer Biobank. Immunohistochemical PODXL expression was examined on full-face sections from all primary tumours and all 140 available lymph node metastases from 31 cases. Membranous PODXL expression was denoted in 18/73 (24,7%) primary tumours, with a high concordance between primary and metastatic lesions. While all negative primary tumours had negative metastases, some PODXL positive primaries had a varying proportion of positive and negative metastatic lymph nodes. PODXL expression was also found to be mainly unaltered in pre- and post-irradiation surgically resected tumour specimens in rectal cancer patients (n=16). The findings in this study suggest that analysis of PODXL expression in the primary tumour is sufficient for its use as a prognostic and treatment predictive biomarker in CRC, also in patients with metastatic disease. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9014177329634352.


A three dimensional visualisation approach to protein heavy-atom structure reconstruction.
A commonly recurring problem in structural protein studies, is the determination of all heavy atom positions from the knowledge of the central α-carbon coordinates. We employ advances in virtual reality to address the problem. The outcome is a 3D visualisation based technique where all the heavy backbone and side chain atoms are treated on equal footing, in terms of the Cα coordinates. Each heavy atom is visualised on the surfaces of a different two-sphere, that is centered at another heavy backbone and side chain atoms. In particular, the rotamers are visible as clusters, that display a clear and strong dependence on the underlying backbone secondary structure. We demonstrate that there is a clear interdependence between rotameric states and secondary structure. Our method easily detects those atoms in a crystallographic protein structure which are either outliers or have been likely misplaced, possibly due to radiation damage. Our approach forms a basis for the development of a new generation, visualization based side chain construction, validation and refinement tools. The heavy atom positions are identified in a manner which accounts for the secondary structure environment, leading to improved accuracy.


A high-frequency EPR study of frozen solutions of Gd(III) complexes: straightforward determination of the zero-field splitting parameters and simulation of the NMRD profiles.
Gd(III) (S = 7/2) polyaminocarboxylates, used as contrast agents for Magnetic Resonance Imaging (MRI), were studied in frozen solutions by High-Frequency-High-Field Electron Paramagnetic Resonance (HF-EPR). EPR spectra recorded at 240 GHz and temperatures below 150 K allowed the direct and straightforward determination of parameters governing the strength of zero-field splitting (ZFS). For the first time, a correlation has been established between the sign of the axial ZFS parameter, D, and the nature of the chelating ligand in Gd(III) complexes: positive and negative signs have been observed for acyclic and macrocyclic complexes, respectively. Furthermore, it has been shown that complexes of the less symmetric acyclic DTPA derivatives possess a substantial rhombicity, E, in contrast to the more symmetric macrocyclic DOTA derivatives, where E is negligible. The results obtained are compatible with recent results of liquid-state EPR and allowed to simulate 1H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles with more directly physically meaningful EPR and NMR parameters over the full frequency range from 0.01 to 50 MHz.


Diurnal variations in the plasma concentrations of mevalonic acid in patients with abetalipoproteinaemia.
Previous studies have demonstrated that changes in the rates of cholesterol biosynthesis can be evaluated by the determination of plasma concentrations of sterol intermediates, including mevalonic acid and lathosterol and that, in normal human subjects, a diurnal rhythm exists in which the highest concentrations of sterol intermediates are observed at night. The factors responsible for this diurnal rhythm in cholesterol synthesis are, however, unknown. To test the hypothesis that the nocturnal increase in cholesterol biosynthesis is attributable to a reduced rate of hepatic uptake of chylomicron remnants at night as compared to higher rates of uptake during the daytime in response to alimentary lipaemia, we have examined the diurnal rhythm of mevalonic acid in six normal volunteers and three patients with phenotypic abetalipoproteinaemia. The latter patients do not absorb appreciable amounts of dietary cholesterol and are unable to synthesize chylomicron particles. Plasma concentrations of mevalonic acid exhibited a diurnal rhythm in the normal subjects, and the highest plasma concentrations were observed between 24.00 hours/04.00 hours. A similar rhythm was observed in the plasma of patients with abetalipoproteinaemia. These results suggest that the nocturnal increase in cholesterol biosynthesis which occurs in humans is not attributable to reduced hepatic uptake of chylomicron remnants at night; further studies are needed to better define those factors which influence the periodicity of cholesterol biosynthesis in humans.


Spa Goers' Repeated Visits for Health and Wellness and the Influential Factors: An Exploratory Study of the UK Spa Goers.
Dissemination of spa services across the globe and its market saturation drive demand for differentiated communication methods. This study aims to explore the influential factors on spa goers' repeated visits and their practical applications in the health and wellness spa industry. The identified factors were used as the measurement variables to examine the relation with spa goers' repeated visits. The proposed concept was tested by a mixed method combining a self-administered questionnaire and semistructured interview with 54 survey participants and 6 interviewees. It was meaningful to use a sample of the UK spa goers from the southwest region since global spa trends stem from the EU spas, and the United Kingdom is one of the market leaders. The data were analyzed using frequency, percentage, multiple logistic regression analysis, and coding process. The survey findings demonstrated that the most significant influential factor on the repeated spa visits is a memorable experience of which showed 13.7 times higher probability than the reference up-to-date facility. The details of memorable experiences were discovered throughout the interviews that include the rediscovery of self, feeling of connectedness, recharge for positive emotions, self-reward through escapism, and experience of noncommercialized local products and attractions. Therefore, using experiential marketing methods can be effective spa service marketing.


Associations of the FTO rs9939609 variant with discrete body fat depots and dietary intake in a multi-ethnic cohort.
The fat mass and obesity associated (FTO) gene has been implicated with obesity and dietary intake predominantly in European populations. We assessed the association between the FTO rs9939609 variant with body fat distribution and dietary intake in a multi-ethnic population. Aboriginal, Chinese, European and South Asian participants living in Canada (n = 706) were assessed for body fat and inner-abdominal fat using imaging techniques, dietary intake and genotyped for the FTO rs9939609 variant. Linear regression was used to study the associations between the minor allele of the variant and measures of adiposity and dietary intake. Minor allele frequencies were: Aboriginals (17%), Chinese (17%), Europeans (39%) and South Asians (31%). The rs9939609 variant was associated with intake of dietary macronutrients in Aboriginals and Europeans only. In the total population, there were positive associations between the rs9939609 minor allele and greater fat mass (0.94 ± 0.56 kg, P = 0.045), per cent body fat (0.7 ± 0.4%, P = 0.031), relative greater subcutaneous abdominal adipose tissue (4.9 ± 2.8%, P = 0.039) and percent daily calories from fat (0.4 ± 0.2%, P = 0.064). Our findings suggest that the FTO rs9939609 minor allele may be associated with dietary intake in adults and is positively associated with regional fat deposition.


Chiropractic management of work-related upper limb disorder complicated by intraosseous ganglion cysts: a case report.
Work-related upper limb disorder (WRULD) encompasses a broad array of occupational upper limb injuries, the most common being carpal tunnel syndrome (CTS). Carpal tunnel syndrome occasionally presents with concomitant ganglion cysts. The purpose of this case report is to describe the chiropractic management of a patient with bilateral WRULD complicated by ganglion cysts. The patient was diagnosed previously with bilateral CTS and presented with common CTS symptoms that were nonresponsive to several previous courses of care. Magnetic resonance imaging revealed bilateral ganglion cysts, and electrodiagnostic studies found left CTS and bilateral radial neuralgia. Right limb findings appeared more consistent with nonspecific arm pain. Chiropractic manipulative therapy, soft-tissue approaches, and physiotherapy modalities were applied to the arms and wrists over a 3-month period. Home care included exercises using elastic tubing and a gyroscopic handheld device. Chiropractic manipulative therapy and other conservative approaches resulted in subjective improvements of decreased hand paresthesias and muscle weakness and objective improvements in range of motion and neurologic deficits. Although the patient's symptoms and function improved, she remained with a level of permanent impairment. This case demonstrates successful chiropractic management of a patient with WRULD complicated by ganglion cysts. Further larger-scale studies are recommended to determine if chiropractic management demonstrates positive outcomes for this condition.


Current path in light emitting diodes based on nanowire ensembles.
Light emitting diodes (LEDs) have been fabricated using ensembles of free-standing (In, Ga)N/GaN nanowires (NWs) grown on Si substrates in the self-induced growth mode by molecular beam epitaxy. Electron-beam-induced current analysis, cathodoluminescence as well as biased μ-photoluminescence spectroscopy, transmission electron microscopy, and electrical measurements indicate that the electroluminescence of such LEDs is governed by the differences in the individual current densities of the single-NW LEDs operated in parallel, i.e. by the inhomogeneity of the current path in the ensemble LED. In addition, the optoelectronic characterization leads to the conclusion that these NWs exhibit N-polarity and that the (In, Ga)N quantum well states in the NWs are subject to a non-vanishing quantum confined Stark effect.


Screening for peptide affinity ligands on CIM monoliths.
Screening of peptide ligands for affinity chromatography usually involves incubation with the target protein in a batch system. In an additional step, peptides with fast binding kinetics have to be selected in respect to satisfactory performance under flow conditions on a support ensuring optimal three-dimensional presentation of the peptide. We have developed a rapid screening system based on peptide synthesis and screening on CIM((R)) disks. The disk size was minimized to fit into microplates usually applied for solid-phase extraction. In combination with a vacuum manifold, semi-automated peptide synthesis and screening for binding to a target protein under simulated chromatography conditions are possible. Various analytical methods can be applied for parallel and automated determination of the quantity, integrity, or activity of the target protein in the flow through or bound to the affinity support. This system also allows parallel screening for suitable chromatographic conditions like running buffer, washing, and elution conditions.


Accuracy of Hospital Discharge Codes in Medicare Claims for Knee and Hip Replacement Patients.
Despite the importance of the hospital discharge destination field ("discharge code" hereafter) for research and payment reform, its accuracy is not well established. The aim of this study was to examine the accuracy of discharge codes in Medicare claims. 2012-2015 Medicare claims of knee and hip replacement patients. We identified patients' discharge location in claims and compared it with the discharge code. We also used a mixed-effects logistic regression to examine the association of patient and hospital characteristics with discharge code accuracy. Approximately 9% of discharge codes were inaccurate. Long-term care hospital discharge codes had the lowest accuracy rate (41%), followed by acute care transfers (72%), inpatient rehabilitation facility (80%), and home discharges (83%). Most misclassifications occurred within 2 broad groups of postacute care settings: home-based and institutional care. The odds of inaccurate discharge codes were higher for Medicaid-enrolled patients and safety-net and low-volume hospitals. Inaccurate hospital discharge coding may have introduced bias in studies relying on these codes (eg, evaluations of Medicare bundled payment models). Inaccuracy was more common among Medicaid-enrolled patients and safety-net and low-volume hospitals, suggesting more potential bias in existing study findings pertaining to these patients and hospitals.


Changes in coagulation in standard laboratory tests and ROTEM in trauma patients between on-scene and arrival in the emergency department.
When trauma patients arrive in the emergency department (ED), coagulopathy frequently is present. The time course, however, in which this coagulopathy develops is poorly understood. No study has fully evaluated the coagulation status, including thromboelastometry on-scene and at hospital arrival. We hypothesized that measured coagulation variables might change when measured at the scene of injury and upon arrival to the ED. We performed a prospective, single-center, observational study investigating coagulation status in 50 trauma patients on-scene and at arrival in the ED. Measurements included arterial blood gases, ROTEM®, protein S100, protein C activity, protein S, Quick value, international normalized ratio, activated partial thromboplastin time, D-dimer, coagulation factor V (FV), coagulation factor XIII (FXIII), fibrinogen, hemoglobin, hematocrit, platelets, and volume and blood products being administered during the first 24 hours. Significant changes between on-scene and the ED were observed for the following values: partial venous oxygen pressure increased and sodium, glucose, and lactate decreased. For EXTEM, INTEM, and APTEM, clotting time and clot formation time increased significantly, whereas maximal clot firmness and angle α decreased significantly (all P ≤ 0.004). For FIBTEM, clotting time increased significantly and maximal clot firmness decreased significantly. In the laboratory, significant reductions in hemoglobin, hematocrit, platelets, activated partial thromboplastin time, fibrinogen, FV, FXIII, protein C activity, protein S, and protein S100 were observed (all P ≤ 0.001). Although most all laboratory and rotational thromboelastometry coagulation tests worsened over time when measured on-scene and in the ED, monitoring coagulation at the scene of trauma does not provide clinically important information in a majority of trauma patients. One hour after injury, significant activation and consumption of fibrinogen, FV, FXIII, protein C activity, and protein S were observed.


In vivo switch to IL-10-secreting T regulatory cells in high dose allergen exposure.
High dose bee venom exposure in beekeepers by natural bee stings represents a model to understand mechanisms of T cell tolerance to allergens in healthy individuals. Continuous exposure of nonallergic beekeepers to high doses of bee venom antigens induces diminished T cell-related cutaneous late-phase swelling to bee stings in parallel with suppressed allergen-specific T cell proliferation and T helper type 1 (Th1) and Th2 cytokine secretion. After multiple bee stings, venom antigen-specific Th1 and Th2 cells show a switch toward interleukin (IL) 10-secreting type 1 T regulatory (Tr1) cells. T cell regulation continues as long as antigen exposure persists and returns to initial levels within 2 to 3 mo after bee stings. Histamine receptor 2 up-regulated on specific Th2 cells displays a dual effect by directly suppressing allergen-stimulated T cells and increasing IL-10 production. In addition, cytotoxic T lymphocyte-associated antigen 4 and programmed death 1 play roles in allergen-specific T cell suppression. In contrast to its role in mucosal allergen tolerance, transforming growth factor beta does not seem to be an essential player in skin-related allergen tolerance. Thus, rapid switch and expansion of IL-10-producing Tr1 cells and the use of multiple suppressive factors represent essential mechanisms in immune tolerance to a high dose of allergens in nonallergic individuals.


Simultaneous measurements of actin filament turnover, filament fraction, and monomer diffusion in endothelial cells.
The analogous techniques of photoactivation of fluorescence (PAF) and fluorescence recovery after photobleaching (FRAP) have been applied previously to the study of actin dynamics in living cells. Traditionally, separate experiments estimate the mobility of actin monomer or the lifetime of actin filaments. A mathematical description of the dynamics of the actin cytoskeleton, however, predicts that the evolution of fluorescence in PAF and FRAP experiments depends simultaneously on the diffusion coefficient of actin monomer, D, the fraction of actin in filaments, FF, and the lifetime of actin filaments, tau (, Biophys. J. 69:1674-1682). Here we report the application of this mathematical model to the interpretation of PAF and FRAP experiments in subconfluent bovine aortic endothelial cells (BAECs). The following parameters apply for actin in the bulk cytoskeleton of subconfluent BAECs. PAF: D = 3.1 +/- 0.4 x 10(-8) cm2/s, FF = 0.36 +/- 0.04, tau = 7.5 +/- 2.0 min. FRAP: D = 5.8 +/- 1.2 x 10(-8) cm2/s, FF = 0.5 +/- 0.04, tau = 4.8 +/- 0.97 min. Differences in the parameters are attributed to differences in the actin derivatives employed in the two studies and not to inherent differences in the PAF and FRAP techniques. Control experiments confirm the modeling assumption that the evolution of fluorescence is dominated by the diffusion of actin monomer, and the cyclic turnover of actin filaments, but not by filament diffusion. The work establishes the dynamic state of actin in subconfluent endothelial cells and provides an improved framework for future applications of PAF and FRAP.


A randomized controlled trial of Moderation-Oriented Cue Exposure.
A randomized controlled trial was conducted to examine the effectiveness of Moderation-Oriented Cue Exposure (MOCE) in comparison to Behavioral Self-Control Training (BSCT). The main hypothesis was that MOCE would be more effective than BSCT among a sample of problem drinkers aiming at moderate drinking. A subsidiary hypothesis was that MOCE would be relatively more effective than BSCT among problem drinkers with higher levels of alcohol dependence. Clients (N = 91; 75% men) were randomly allocated to either MOCE or BSCT. Treatment was delivered in weekly sessions by two trained therapists, in a nested design in which therapists switched to the alternative treatment modality approximately halfway through the trial. Follow-up was carried out 6 months following posttreatment assessment, with 85% successful contact. There was no evidence for the general superiority of MOCE over BSCT. The subsidiary hypothesis was not confirmed. A subsample of clients (n = 14) showing levels of dependence at baseline above the commonly accepted cut-point for a moderation goal (Severity of Alcohol Dependence Questionnaire [SADQ] > 29) showed outcomes at least as favorable as those below the cut-point. The validity of self-reports of alcohol consumption and problems was supported by significant relationships with liver function tests (gamma-glutamyl transferase and alanine transferase). These results provide no grounds for the replacement of BSCT by MOCE in routine, moderation-oriented treatment practice. Assuming they prefer it to abstinence and that it is not contra-indicated on other grounds, there seems no reason why clients showing a higher level of dependence (SADQ = 30-45) should not be offered a moderation goal.


MedMon: securing medical devices through wireless monitoring and anomaly detection.
Rapid advances in personal healthcare systems based on implantable and wearable medical devices promise to greatly improve the quality of diagnosis and treatment for a range of medical conditions. However, the increasing programmability and wireless connectivity of medical devices also open up opportunities for malicious attackers. Unfortunately, implantable/wearable medical devices come with extreme size and power constraints, and unique usage models, making it infeasible to simply borrow conventional security solutions such as cryptography. We propose a general framework for securing medical devices based on wireless channel monitoring and anomaly detection. Our proposal is based on a medical security monitor (MedMon) that snoops on all the radio-frequency wireless communications to/from medical devices and uses multi-layered anomaly detection to identify potentially malicious transactions. Upon detection of a malicious transaction, MedMon takes appropriate response actions, which could range from passive (notifying the user) to active (jamming the packets so that they do not reach the medical device). A key benefit of MedMon is that it is applicable to existing medical devices that are in use by patients, with no hardware or software modifications to them. Consequently, it also leads to zero power overheads on these devices. We demonstrate the feasibility of our proposal by developing a prototype implementation for an insulin delivery system using off-the-shelf components (USRP software-defined radio). We evaluate its effectiveness under several attack scenarios. Our results show that MedMon can detect virtually all naive attacks and a large fraction of more sophisticated attacks, suggesting that it is an effective approach to enhancing the security of medical devices.


T cell-derived lymphotoxin regulates liver regeneration.
The ability of the liver to regenerate hepatic mass is essential to withstanding liver injury. The process of liver regeneration is tightly regulated by distinct signaling cascades involving components of the innate immune system, cytokines, and growth factors. However, the role of the adaptive immune system in regulation of liver regeneration is not well-defined. The role of adaptive immune system in liver regeneration was investigated in lymphocyte-deficient mice and in conditional lymphotoxin-deficient mice. A model of liver regeneration after 70% partial hepatectomy was used, followed by examination of liver pathology, survival, DNA synthesis, and cytokine expression. We found that mice deficient in T cells show a reduced capacity for liver regeneration following partial hepatectomy. Furthermore, surface lymphotoxin, provided by T cells, is critical for liver regeneration. Mice specifically deficient in T-cell lymphotoxin had increased liver damage and a reduced capacity to initiate DNA synthesis after partial hepatectomy. Transfer of splenocytes from wild-type but not lymphotoxin-deficient mice improved liver regeneration in T cell-deficient mice. We found that an agonistic antibody against the lymphotoxin beta receptor was able to facilitate liver regeneration by reducing liver injury, increasing interleukin-6 production, hepatocyte DNA synthesis, and survival of lymphocyte-deficient (Rag) mice after partial hepatectomy. The adaptive immune system directly regulates liver regeneration via a T cell-derived lymphotoxin axis, and pharmacological stimulation of lymphotoxin beta receptor might represent a novel therapeutic approach to improve liver regeneration.


A practical guide for the care of patients with end-stage renal disease near the end of life.
Most patients who rely on dialysis for treatment of end-stage renal disease (ESRD) never receive a kidney transplant. Therefore, it is important for nephrology providers to feel comfortable discussing the role of dialysis near the end of life (EOL). Advance care planning (ACP) is an ongoing process of learning patient values and goals in an effort to outline preferences for current and future care. This review presents a framework for how to incorporate ACP in the care of dialysis patients throughout the kidney disease course and at the EOL. Early ACP is useful for all dialysis patients and should ideally begin in the absence of clinical setbacks. Check-in conversations can be used to continue longitudinal discussions with patients and identify opportunities for symptom management and support. Lastly, triggered ACP is useful to clarify care preferences for patients with worsening clinical status. Practical tools include prognostication models to identify patients at risk for decline; ACP documents to operationalize patient care preferences; and communication guidance for engaging in these important conversations. Interdisciplinary teams with expertise from social work, palliative care, and hospice can be helpful at various stages and are discussed here.


Sparse SPM: Group Sparse-dictionary learning in SPM framework for resting-state functional connectivity MRI analysis.
Recent studies of functional connectivity MR imaging have revealed that the default-mode network activity is disrupted in diseases such as Alzheimer's disease (AD). However, there is not yet a consensus on the preferred method for resting-state analysis. Because the brain is reported to have complex interconnected networks according to graph theoretical analysis, the independency assumption, as in the popular independent component analysis (ICA) approach, often does not hold. Here, rather than using the independency assumption, we present a new statistical parameter mapping (SPM)-type analysis method based on a sparse graph model where temporal dynamics at each voxel position are described as a sparse combination of global brain dynamics. In particular, a new concept of a spatially adaptive design matrix has been proposed to represent local connectivity that shares the same temporal dynamics. If we further assume that local network structures within a group are similar, the estimation problem of global and local dynamics can be solved using sparse dictionary learning for the concatenated temporal data across subjects. Moreover, under the homoscedasticity variance assumption across subjects and groups that is often used in SPM analysis, the aforementioned individual and group analyses using sparse dictionary learning can be accurately modeled by a mixed-effect model, which also facilitates a standard SPM-type group-level inference using summary statistics. Using an extensive resting fMRI data set obtained from normal, mild cognitive impairment (MCI), and Alzheimer's disease patient groups, we demonstrated that the changes in the default mode network extracted by the proposed method are more closely correlated with the progression of Alzheimer's disease.


Early life adversity reduces affiliative behavior with a stressed cagemate and leads to sex-specific alterations in corticosterone responses in adult mice.
Experiencing early life adversity (ELA) alters stress physiology and increases the risk for developing psychiatric disorders. The social environment can influence dynamics of stress responding and buffer and/or transfer stress across individuals. Yet, the impact of ELA on sensitivity to the stress of others and social behavior following stress is unknown. Here, to test the impact of ELA on social and physiological responses to stress, circulating blood corticosterone (CORT) and social behaviors were assessed in adult male and female mice reared under limited bedding and nesting (LBN) or control conditions. To induce stress, one cagemate of a pair-housed cage underwent a footshock paradigm and was then returned to their unshocked partner. CORT was measured in both groups of mice 20 or 90 min after stress exposure, and social behaviors were recorded and analyzed. ELA rearing influenced the CORT response to stress in a sex-specific manner. In males, both control and ELA-reared mice exhibited similar stress transfer to unshocked cagemates and similar CORT dynamics. In contrast, ELA females showed a heightened stress transfer to unshocked cagemates, and sustained elevation of CORT relative to controls, indicating enhanced stress contagion and a failure to terminate the stress response. Behaviorally, ELA females displayed decreased allogrooming and increased investigative behaviors, while ELA males showed reduced huddling. Together, these findings demonstrate that ELA influenced HPA axis dynamics, social stress contagion and social behavior. Further research is needed to unravel the underlying mechanisms and long-term consequences of ELA on stress systems and their impact on behavioral outcomes.


Economic considerations support C-reactive protein testing alongside malaria rapid diagnostic tests to guide antimicrobial therapy for patients with febrile illness in settings with low malaria endemicity.
Malaria is no longer a common cause of febrile illness in many regions of the tropics. In part, this success is a result of improved access to accurate diagnosis and effective anti-malarial treatment, including in many hard-to-reach rural areas. However, in these settings, management of other causes of febrile illness remains challenging. Health systems are often weak and other than malaria rapid tests no other diagnostics are available. With millions of deaths occurring annually due to treatable bacterial infections and the ever increasing spread of antimicrobial resistance, improvement in the management of febrile illness is a global public health priority. Whilst numerous promising point-of-care diagnostics are in the pipeline, substantial progress can be made in the interim with existing tools: C-reactive protein (CRP) is a highly sensitive and moderately specific biomarker of bacterial infection and has been in clinical use for these purposes for decades, with dozens of low-cost devices commercially available. This paper takes a health-economics approach to consider the possible advantages of CRP point-of-care tests alongside rapid diagnostic tests for malaria, potentially in a single multiplex device, to guide antimicrobial therapy for patients with febrile illness. Three rudimentary assessments of the costs and benefits of this approach all indicate that this is likely to be cost-effective when considering the incremental costs of the CRP tests as compared with either (i) the improved health outcomes for patients with bacterial illnesses; (ii) the costs of antimicrobial resistance averted; or (iii) the economic benefits of better management of remaining malaria cases and shorter malaria elimination campaigns in areas of low transmission. While CRP-guided antibiotic therapy alone cannot resolve all challenges associated with management of febrile illness in remote tropical settings, in the short-term a multiplexed CRP and malaria RDT could be highly cost-effective and utilize the well-established funding and distribution systems already in place for malaria RDTs. These findings should spark further interest amongst industry, academics and policy-makers in the development and deployment of such diagnostics, and discussion on their geographically appropriate use.


Lipopolysaccharide-Induced Increase in Intestinal Epithelial Tight Permeability Is Mediated by Toll-Like Receptor 4/Myeloid Differentiation Primary Response 88 (MyD88) Activation of Myosin Light Chain Kinase Expression.
Lipopolysaccharides (LPSs) are a major component of the Gram-negative bacterial cell wall and play an important role in mediating intestinal inflammatory responses in inflammatory bowel disease. Although recent studies suggested that physiologically relevant concentrations of LPS (0 to 1 ng/mL) cause an increase in intestinal epithelial tight junction (TJ) permeability, the mechanisms that mediate an LPS-induced increase in intestinal TJ permeability remain unclear. Herein, we show that myosin light chain kinase (MLCK) plays a central role in the LPS-induced increase in TJ permeability. Filter-grown Caco-2 intestinal epithelial monolayers and C57BL/6 mice were used as an in vitro and in vivo intestinal epithelial model system, respectively. LPS caused a dose- and time-dependent increase in MLCK expression and kinase activity in Caco-2 monolayers. The pharmacologic MLCK inhibition and siRNA-induced knock-down of MLCK inhibited the LPS-induced increase in Caco-2 TJ permeability. The LPS increase in TJ permeability was mediated by toll-like receptor 4 (TLR-4)/MyD88 signal-transduction pathway up-regulation of MLCK expression. The LPS-induced increase in mouse intestinal permeability also required an increase in MLCK expression. The LPS-induced increase in intestinal permeability was inhibited in MLCK-/- and TLR-4-/- mice. These data show, for the first time, that the LPS-induced increase in intestinal permeability was mediated by TLR-4/MyD88 signal-transduction pathway up-regulation of MLCK. Therapeutic targeting of these pathways can prevent an LPS-induced increase in intestinal permeability.


A look at working-age caregivers' roles, health concerns, and need for support.
The role of informal caregivers is becoming increasingly important as the U.S. population continues to age and cost-containment strategies promote shorter hospital stays. There are currently 16 million working-age adults caring for a sick or disabled family member, according to data from the Commonwealth Fund Biennial Health Insurance Survey. Caregivers are less likely to be working, to miss days of work when they are employed, and to lack health insurance coverage. This may leave them financially vulnerable and unable to obtain needed health care. Indeed, one-half of caregivers reported not getting care because of cost issues, and three of five caregivers experienced problems with medical bills. Policies to expand Medicaid and Medicare would improve caregivers' ability to access health care for themselves and their families, as well as help eliminate the financial strain of going without health insurance.


Machine learning for cell classification and neighborhood analysis in glioma tissue.
Multiplexed and spatially resolved single-cell analyses that intend to study tissue heterogeneity and cell organization invariably face as a first step the challenge of cell classification. Accuracy and reproducibility are important for the downstream process of counting cells, quantifying cell-cell interactions, and extracting information on disease-specific localized cell niches. Novel staining techniques make it possible to visualize and quantify large numbers of cell-specific molecular markers in parallel. However, due to variations in sample handling and artifacts from staining and scanning, cells of the same type may present different marker profiles both within and across samples. We address multiplexed immunofluorescence data from tissue microarrays of low-grade gliomas and present a methodology using two different machine learning architectures and features insensitive to illumination to perform cell classification. The fully automated cell classification provides a measure of confidence for the decision and requires a comparably small annotated data set for training, which can be created using freely available tools. Using the proposed method, we reached an accuracy of 83.1% on cell classification without the need for standardization of samples. Using our confidence measure, cells with low-confidence classifications could be excluded, pushing the classification accuracy to 94.5%. Next, we used the cell classification results to search for cell niches with an unsupervised learning approach based on graph neural networks. We show that the approach can re-detect specialized tissue niches in previously published data, and that our proposed cell classification leads to niche definitions that may be relevant for sub-groups of glioma, if applied to larger data sets.


Residential care for the elderly.
This article maps variations in a standardized way in residential care for elderly people in three Western nations. Measured by the number of available places per person aged sixty-five and over and by the number of staff members per bed in nursing homes, the United Kingdom has the most highly developed standards. The United States ranks second, with Germany lagging considerably behind. The variations are explained by four variables: the pressure of the problem, as defined by the percentage of the population aged sixty-five and over; the caretaker potential in the family system, which alleviates this pressure; the structure and financing of the supply of residential care; and decision-making procedures in health care policy-making. My analysis emphasizes the last two variables. In the United Kingdom and the United States, the public and private providers who supply care have either political or market incentives to expand their services. Germany's mix of public and private, by contrast, is dominated by voluntary associations that are neither responsible to an electorate nor allowed to make profits. Thus, their clients do not have opportunities to articulate their needs. Health care decision making in Germany takes place through a collective bargaining process between the sickness funds and the providers. In such a system, the interests of groups who are not represented at the negotiation table--such as the elderly--tend to be neglected. A national health system of the British type links political decision makers via the election mechanism more closely to the concerns of the public. As older people represent growing proportions of the electorate, their needs find more adequate consideration in the policy process. In the United States, political officeholders also have to pay attention to the needs of increasingly organized older people, since the tax-financed and federally regulated Medicaid system is largely responsible for financing long-term care for the elderly.


Borrelia burgdorferi activates a T helper type 1-like T cell subset in Lyme arthritis.
18 cloned T cell lines reactive with Borrelia burgdorferi proteins, all CD3+4+8-TCR-alpha/beta+ and restricted by HLA class II proteins, were isolated from four patients with chronic Lyme arthritis. Analysis of these T cell clones indicated that the T cell response to the Lyme disease spirochete is not oligoclonally restricted; yet all produced the same pattern of lymphokines, resembling that of murine type 1 T helper cells, after antigen-specific or nonspecific stimulation. Therefore, a subset of human CD4+ T cells, with a distinct profile of lymphokine secretion, is selectively activated by the pathogen inciting this chronic inflammatory disease.


Inducible costimulator protein (ICOS) controls T helper cell subset polarization after virus and parasite infection.
It has been shown that certain pathogens can trigger efficient T cell responses in the absence of CD28, a key costimulatory receptor expressed on resting T cells. Inducible costimulator protein (ICOS) is an inducible costimulator structurally and functionally related to CD28. Here, we show that in the absence of CD28 both T helper cell type 1 (Th1) and Th2 responses were impaired but not abrogated after infection with lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and the nematode Nippostrongylus brasiliensis. Inhibition of ICOS in CD28-deficient mice further reduced Th1/Th2 polarization. Blocking of ICOS alone had a limited but significant capacity to downregulate Th subset development. In contrast, cytotoxic T lymphocyte (CTL) responses, which are regulated to a minor and major extent by CD28 after LCMV and VSV infection, respectively, remained unaffected by blocking ICOS. Together, our results demonstrate that ICOS regulates both CD28-dependent and CD28-independent CD4(+) subset (Th1 and Th2) responses but not CTL responses in vivo.


Inclusion of Sex and Gender in Emergency Medicine Research-A 2018 Update.
The objectives were to 1) evaluate the inclusion of sex and gender in publications by emergency medicine (EM) researchers following the 2014 federal mandate and an Academic Emergency Medicine consensus conference on sex- and gender-based research and 2) assess trends compared with 2011 status report that showed 29% studies used sex and gender in the study design and 2% reported it as a primary outcome. Using MEDLINE, the term "emergency" was used to identify all English-language studies of adult humans published between 2014 and 2017 as EM affiliated (i.e., the first, second, or last author belonged to an EM section, division, center, or institution functioning as emergency department). Four trained abstractors reviewed the data using a standardized data abstraction form. The search revealed 6,442 articles using the selected "emergency" terms, and 2,628 original studies coded as EM-affiliated publications were reviewed, 2,340 met inclusion criteria, and 2,336 were analyzed. This compared to 750 articles reviewed in 2011 using similar search strategy. The adjusted inter-rater reliability for data abstraction was 97% (95% confidence interval [CI] = 95.4%-98.6%]. The leading study areas contributing the most articles were cardiovascular (17.5%), administration/crowding (15.8%), infectious diseases (9.2%), trauma/injury (9.2%), emergency medical services (6.1%), and pulmonary (6.1%). Eighty-six percent (n = 1,921) reported the sex/gender composition of the sample and 0.4% (n = 8) reported transgender identity. Thirty-four percent used sex/gender in the study design, with 27% (n = 609) reporting it as a control variable, 24% (n = 543) as an independent variable, and 2% using sex/gender as primary outcome. Studies funded by federal sources were significantly more likely to include sex/gender in the study design than other sources of funding (odds ratio = 1.77; 95% CI = 1.4-2.2). Compared to 2011, we noted an increase in the number of EM scholarship and use of sex and gender in study design, yet the proportion evaluating it as a primary outcome remained unchanged.


Control of C3N4 and C4N3 carbon nitride nanosheets' electronic and magnetic properties through embedded atoms.
In the present work, the effect of various embedded atom impurities on tuning electronic and magnetic properties of C3N4 and C4N3 nanosheets have been studied using first-principles calculations. Our calculations show that C3N4 is a semiconductor and it exhibits extraordinary electronic properties such as dilute-magnetic semiconductor (with H, F, Cl, Be, V, Fe and Co); metal (with N, P, Mg and Ca), half-metal (with Li, Na, K, Al, Sc, Cr, Mn, and Cu) and semiconductor (with O, S, B, C, Si, Ti, Ni and Zn) with the band gaps in the range of 0.3-2.0 eV depending on the species of embedded atom. The calculated electronic properties reveal that C4N3 is a half-metal and it retains half-metallic character with embedded H, O, S, F, B, N, P, Be, Mg, Al, Sc, V, Fe, Ni and Zn atoms. The substitution of Cl, C, Cr and Mn atoms create ferromagnetic-metal character in the C4N3 nanosheet, embedded Co and Cu atoms exhibit a dilute-magnetic semiconductor nature, and embedded Ti atoms result in the system becoming a semiconductor. Therefore, our results reveal the fact that the band gap and magnetism can be modified or induced by various atom impurities, thus, offering effective possibilities to tune the electronic and magnetic properties of C3N4 and C4N3 nanosheets.


Assessment of subjective refraction with a clinical adaptive optics visual simulator.
To clinically validate an adaptive optics visual simulator (VAO) that measures subjective refraction and visual acuity. Optics Laboratory, University of Murcia, Murcia, Spain. Prospective case series. Using the adaptive optics visual simulator, 2 examiners measured the subjective refraction and visual acuity in healthy eyes of volunteers; 1 examiner also used a trial frame as a gold standard. The interexaminer reproducibility and agreement with the gold standard were estimated using the following statistical parameters: limits of agreement from Bland-Altman analysis, significance between differences (P value), and intraclass correlation coefficient (ICC). Seventy-six eyes of 38 volunteers were measured. Interexaminer reproducibility for subjective refraction was excellent (ICC ≥0.96; P > .05), with low 95% confidence interval (CI) values for the power vectors M (spherical equivalent of the given refractive error), J0 (Jackson cross-cylinder, axes at 180 degrees and 90 degrees), and J45 (Jackson cross-cylinder, axes at 45 degrees and 135 degrees) (±0.51 diopter [D], ±0.14 D, and ±0.14 D, respectively). No significant differences in subjective refraction and visual acuity were found between the visual simulator and gold standard (P > .05), with 95% CIs for M, J0, and J45 (subjective refraction) of ±0.67 D, ±0.14 D, and ±0.16 D, respectively, and a ±0.10 logarithm of the minimum angle of resolution (visual acuity). Subjective refraction results using the adaptive optics visual simulator agreed with those of the gold standard and can be used as the baseline for visual simulation of any optical corneal profile or intraocular lens design for refractive surgery patients.


Twenty-Eight Orders of Parametric Resonance in a Microelectromechanical Device for Multi-band Vibration Energy Harvesting.
This paper contends to be the first to report the experimental observation of up to 28 orders of parametric resonance, which has thus far only been envisioned in the theoretical realm. While theory has long predicted the onset of n orders of parametric resonance, previously reported experimental observations have been limited up to about the first 5 orders. This is due to the rapid narrowing nature of the frequency bandwidth of the higher instability intervals, making practical accessibility increasingly more difficult. Here, the authors have experimentally confirmed up to 28 orders of parametric resonance in a micromachined membrane resonator when electrically undamped. While the implication of this finding spans across the vibration dynamics and transducer application spectrum, the particular significance of this work is to broaden the accumulative operational frequency bandwidth of vibration energy harvesting for enabling self-powered microsystems. Up to 5 orders were recorded when driven at 1.0 g of acceleration across a matched load of 70 kΩ. With a natural frequency of 980 Hz, the fundamental mode direct resonance had a -3 dB bandwidth of 55 Hz, in contrast to the 314 Hz for the first order parametric resonance; furthermore, the half power bands of all 5 orders accumulated to 478 Hz.


A case study and a computational simulation of the European Union draft technical guidance documents for chemical safety assessment of mixtures: limitations and a tentative alternative.
Two different methods, Key Critical Component (KCC) and Composite Reciprocal (CR), are used to derive Predicted No Effect Concentration (PNECs) and Derived No Effect Level (DNELs) that are employed in mixture risk assessment. A case study was conducted on coating products and a computational simulation of the KCC and CR methods. The KCC method considers only one key critical component as the whole mixture of equal danger, whereas the CR method indirectly considers the contribution of each component to mixture toxicity. Computational simulation is the first approach that adopts a theoretical perspective in discussing the causes of different outcomes between models and how the two methods should be applied for regulatory purposes in terms of concept, implementation, and performance. The deviation between the two models was highly dependent on the number of mixture components having similarly weighted DNELs (or PNECs). Therefore, if risk assessment using the KCC or CR method needs to be achieved, then the number of mixture components with similarly weighted DNELs (or PNECs) should be checked first. In this study, as a tentative alternative to the existing KCC and CR methods, a tiered approach combining Enhanced KCC (e-KCC) and CR methods was proposed and discussed.


Managing the marine aquarium trade: revealing the data gaps using ornamental polychaetes.
The marine aquarium industry has great potential to generate jobs in low-income coastal communities creating incentives for the maintenance of a healthy coral reef, if effectively managed. In the absence of current monitoring or legislation to govern the trade, baseline information regarding the species, number and source location of animals traded is missing despite being critical for its successful management and sustainability. An industry assessment to establish the number and provenance of species of ornamental polychaetes (sabellids and serpulids) traded was undertaken across UK wholesalers and retailers. Six geographical regions exporting fan worms were identified. Singapore contributed the highest percentage of imports, but of only one worm "type" whereas Bali, the second largest source, supplied five different worm "types". Over 50% of UK retailers were supplied by one wholesaler while the remainder were stocked by a mixture of one other wholesaler and/or direct imports from the source country. We estimate that up to 18,500 ornamental polychaetes (16,980 sabellids and 1,018 serpulids) are sold annually in the UK revealing a drastic underestimation of currently accepted trade figures. Incorrect identification (based on exporting region or visual characteristics) of traded animals exacerbates the inaccuracy in market quantification, although identification of preserved sabellids using published keys proved just as inconclusive with high within-species variability and the potential for new or cryptic species. A re-description of the polychaete groups traded using a combination of molecular and morphological techniques is necessary for effective identification and market quantification. This study provides the first assessment of ornamental polychaetes but more importantly highlights the issues surrounding the collection of baseline information necessary to manage the aquarium trade. We recommend that future management should be community based and site-specific with financial and educational support from NGOs, local governments and industry members.


High dietary calcium intake decreases bone mobilization during pregnancy in humans.
Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. To evaluate the association of calcium intake and bone demineralization during pregnancy. At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (beta=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300 mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).


Low-dimensional organization of global brain states of reduced consciousness.
Brain states are frequently represented using a unidimensional scale measuring the richness of subjective experience (level of consciousness). This description assumes a mapping between the high-dimensional space of whole-brain configurations and the trajectories of brain states associated with changes in consciousness, yet this mapping and its properties remain unclear. We combine whole-brain modeling, data augmentation, and deep learning for dimensionality reduction to determine a mapping representing states of consciousness in a low-dimensional space, where distances parallel similarities between states. An orderly trajectory from wakefulness to patients with brain injury is revealed in a latent space whose coordinates represent metrics related to functional modularity and structure-function coupling, increasing alongside loss of consciousness. Finally, we investigate the effects of model perturbations, providing geometrical interpretation for the stability and reversibility of states. We conclude that conscious awareness depends on functional patterns encoded as a low-dimensional trajectory within the vast space of brain configurations.


Does prolonged length of stay in the emergency department affect outcome for stroke patients?
Conflicting data exist regarding the association between the length of stay (LOS) of critically ill patients in the emergency department (ED) and their subsequent outcome. However, such patients are an overall heterogeneous group, and we therefore sought to study the association between EDLOS and outcomes in a specific subgroup of critically ill patients, namely those with acute ischemic stroke/transient ischemic attack (AIS/TIA). This was a retrospective review of adult patients with a discharge diagnosis of AIS/TIA presenting to an ED between July 2009 and February 2010. We collected demographics, EDLOS, arrival stroke severity (National Institutes of Health Stroke Scale - NIHSS), intravenous tissue plasminogen activator (IV tPA) use, functional outcome at discharge, discharge destination and hospital-LOS. We analyzed relationship between EDLOS, outcomes and discharge destination after controlling for confounders. 190 patients were included in the cohort. Median EDLOS was 332 minutes (Inter-Quartile Range -IQR: 250.3-557.8). There was a significant inverse linear association between EDLOS and hospital-LOS (p=0.049). Patients who received IV tPA had a shorter median EDLOS (238 minutes, IQR: 194-299) than patients who did not (median: 387 minutes, IQR: 285-588 minutes; p<0.0001). There was no significant association between EDLOS and poor outcome (p=0.40), discharge destination (p=0.20), or death (p=0.44). This remained true even after controlling for IV tPA use, NIHSS and hospital-LOS; and did not change even when analysis was restricted to AIS patients alone. There was no significant association between prolonged EDLOS and outcome for AIS/TIA patients at our institution. We therefore suggest that EDLOS alone is an insufficient indicator of stroke care in the ED, and that the ED can provide appropriate acute care for AIS/TIA patients. [West J Emerg Med. 2014;15(3):267-275.].


L1 interaction with ankyrin regulates mediolateral topography in the retinocollicular projection.
Dynamic modulation of adhesion provided by anchorage of axonal receptors with the cytoskeleton contributes to attractant or repellent responses that guide axons to topographic targets in the brain. The neural cell adhesion molecule L1 engages the spectrin-actin cytoskeleton through reversible linkage of its cytoplasmic domain to ankyrin. To investigate a role for L1 association with the cytoskeleton in topographic guidance of retinal axons to the superior colliculus, a novel mouse strain was generated by genetic knock-in that expresses an L1 point mutation (Tyr1229His) abolishing ankyrin binding. Axon tracing revealed a striking mistargeting of mutant ganglion cell axons from the ventral retina, which express high levels of ephrinB receptors, to abnormally lateral sites in the contralateral superior colliculus, where they formed multiple ectopic arborizations. These axons were compromised in extending interstitial branches in the medial direction, a normal response to the high medial to low lateral SC gradient of ephrinB1. Furthermore, ventral but not dorsal L1(Y1229H) retinal cells were impaired for ephrinB1-stimulated adhesion through beta1 integrins in culture. The retinocollicular phenotype of the L1(Tyr1229His) mutant provides the first evidence that L1 regulates topographic mapping of retinal axons through adhesion mediated by linkage to the actin cytoskeleton and functional interaction with the ephrinB/EphB targeting system.


Noradrenaline enhances temporal auditory contrast and neuronal timing precision in the cochlear nucleus of the mustached bat.
In the mustached bat, Pteronotus parnellii, noradrenaline (NA) was applied iontophoretically to single units in the anteroventral cochlear nucleus. NA suppressed tonic components of auditory responses and enhanced phasic onset responses to pure tone stimuli. The enhancement of onset activity was most pronounced in awake bats and was due to a decrease in the latency jitter of the first tone-evoked spikes from 0.55 msec in controls to 0.28 msec during NA application. In addition, NA reduced spontaneous neuronal activity. Noradrenergic antagonists suppressed phasic onset activity and increased the latency jitter of onset spikes. Opposite to the effect of NA, the tonic response component increased during application of the beta-antagonist propranolol but decreased during injection of the alpha 1-antagonist corynanthine. Other putative transmitter substances tested, nonselectively depressed both phasic and tonic response components (GABA, glycine) or increased both components either similarly or had more pronounced effects on the tonic response components (ACh, glutamate). Thus, NA specifically enhances auditory temporal contrast in favor of transients and improves neuronal timing precision, which may be of relevance for auditory tasks like passive sound localization, echolocation, and recognition of temporal patterns.


Route-learning strategies in typical and atypical development; eye tracking reveals atypical landmark selection in Williams syndrome.
Successful navigation is crucial to everyday life. Individuals with Williams syndrome (WS) have impaired spatial abilities. This includes a deficit in spatial navigation abilities such as learning the route from A to B. To-date, to determine whether participants attend to landmarks when learning a route, landmark recall tasks have been employed after the route learning experience. Here, we combined virtual reality and eye tracking technologies, for the first time, to measure landmark use in typically developing (TD) children and participants with WS during route-learning. Nineteen individuals with WS were asked to learn a route in a sparse environment (few landmarks) and in a rich environment (many landmarks) whilst their eye movements were recorded. Looking times towards landmarks were compared to TD children aged 6, 8 and 10 years. Changes in attention to landmarks during the learning process were also recorded. The WS group made fewer looks to landmarks overall, but all participants looked for longer at landmarks that were at junctions and along the paths of the maze than landmarks that were in the distance. Few differences were observed in route learning between the sparse and rich environments. In contrast to the TD groups, those in the WS group were as likely to look at non-unique landmarks as landmarks at junctions and on paths. The current results demonstrate that attention to landmarks during route learning reflects the types of landmarks remembered in memory tasks, that individuals with WS can learn a route if given sufficient exposure, but that this is accomplished within the context of an impaired ability to select appropriate landmarks.


A Comparison of Early, Late, and No Treatment of Intensive Care Unit Delirium With Antipsychotics: A Retrospective Cohort Study.
To investigate the effect of early versus late versus no antipsychotic administration on intensive care unit (ICU) delirium. This retrospective cohort study was conducted in 2 adult medical ICUs at a single tertiary care center in Boston, Massachusetts, from October 1, 2015, to May 31, 2016. The study included 322 patients stratified into those who first received antipsychotics < 48 hours after first positive or unscorable (due to sedation) modified Confusion Assessment Method (CAM-ICU-m) (early), > 48 hours after first positive or unscorable CAM-ICU-m (late), and never received antipsychotics. Primary outcomes were hours alive without delirium or coma and likelihood of delirium-coma resolution. Secondary outcomes included ventilator-free hours, likelihood of extubation, and 10-day mortality. In post hoc exploratory analyses, outcomes were reanalyzed excluding comatose patients. Mean ± SD delirium-coma-free hours were 63 ± 87 for patients who received antipsychotics early, 66 ± 92 for those who received antipsychotics late, and 89 ± 107 for those who never received antipsychotics (P = .71). Antipsychotic exposure did not impact delirium-coma resolution. Mean ventilator-free hours were 103 ± 87 for patients who received antipsychotics early, 90 ± 83 for those who received antipsychotics late, and 89 ± 101 for patients who never received antipsychotics (P = .11). The hazard ratio (HR) for 10-day mortality among patients who received antipsychotics early was 0.68 (95% CI, 0.37-1.22) and 0.30 (95% CI, 0.10-0.88) for those who received antipsychotics late compared to those who never received antipsychotics (P = .03). After excluding comatose patients, the effect of antipsychotics on 10-day mortality was no longer observed (early HR = 0.57, 95% CI, 0.30-1.07; late HR = 0.57, 95% CI, 0.28-1.18; never HR = 1 [reference]; P = .14). Antipsychotics were not associated with changes in delirium-coma-free hours or ventilator-free hours.


An inclusive fitness analysis of altruism on a cyclical network.
A recent model studies the evolution of cooperation on a network, and concludes with a result connecting the benefits and costs of interactions and the number of neighbours. Here, an inclusive fitness analysis is conducted of the only case solved analytically, of a cycle, and the identical result is obtained. This brings the result within a biologically familiar framework. It is notable that the benefits and costs in the inclusive fitness framework need to be derived, and are not the benefits and costs that are the parameters in the original model. The relatedness is a quadratic function of position in a cycle of size N: an individual is related by 1 to itself, by (N - 5)/(N + 1) to an immediate neighbour, and by very close to -1/2 to the most distant individuals. The inclusive fitness analysis explains hitherto puzzling features of the results.


Hope, truth, and preparing for death: perspectives of surrogate decision makers.
Although many physicians worry that openly discussing a poor prognosis will cause patients and families to lose hope, surrogate decision makers' perspectives on this topic are largely unknown. To determine surrogate decision makers' attitudes toward balancing hope and telling the truth when discussing prognosis. Prospective, mixed-methods cohort study. 4 intensive care units at the University of California, San Francisco, Medical Center, San Francisco, California. 179 surrogate decision makers for incapacitated patients at high risk for death. One-on-one, semistructured interviews with surrogates were conducted on the patients' 5th day of receiving mechanical ventilation. Constant comparative methods were used to inductively develop a framework to describe participants' responses. Validation methods included multidisciplinary analysis and member checking. Overall, 93% (166 of 179) of surrogates felt that avoiding discussions about prognosis is an unacceptable way to maintain hope. The main explanatory theme was that timely discussion of prognosis is essential to allow family members to prepare emotionally and logistically for the possibility of a patient's death. Other themes that emerged included surrogates' belief that an accurate understanding of a patient's prognosis allows them to better support the patient and each other, a moral aversion to the idea of false hope, the perception that physicians have an obligation to discuss prognosis, and the notion that some surrogates look to physicians primarily for truth and seek hope elsewhere. A few surrogates (6 of 179) felt that physicians should withhold prognostic information because of a belief that discussing death could be emotionally damaging to the family or could negatively affect the patient's health. The authors did not longitudinally assess whether early disclosure about prognosis predicts fewer adverse bereavement outcomes. Most surrogates of critically ill patients do not view withholding prognostic information as an acceptable way to maintain hope, largely because timely discussions about prognosis help families begin to prepare emotionally, existentially, and practically for the possibility that a patient will die.


Time trends in the incidence and prevalence of multiple sclerosis in Norway during eight decades.
Norway has been subjected to numerous epidemiological investigations on the prevalence and incidence of multiple sclerosis (MS), dating back to 1935. The objective of this study was to review the studies on the prevalence and incidence of MS in Norway, provide an update on the prevalence of MS in Norway, and describe the time trends in the prevalence and incidence of MS in relation to risk factors, case ascertainment, and data. We performed a systematic search on PubMed and MEDLINE up to November 2014 using the search string 'multiple sclerosis prevalence in Norway' or 'multiple sclerosis incidence in Norway'. In addition, we scrutinized the reference lists of the publications identified for relevant citations. We retrieved data on the distribution of MS in Norway on December 31, 2013 from the Norwegian Multiple Sclerosis Registry and Biobank and the Norwegian Patient Registry. We identified 29 articles. From 1961 to 2014, the reported prevalence of MS increased from 20 to 203 per 100,000 inhabitants, and the incidence increased from 1.9 to 8.0 per 100,000. The nationwide crude prevalence in Norway, based on the Norwegian Patient Registry, was 208 per 100,000 on December 31, 2013. The reported prevalence of MS in Norway has increased 10-fold, with several possible causes. During eight decades, neurological health services have generally become more accessible to the population, and transforming diagnostic criteria has made the diagnosis of MS more precise and valid. There have also been changes in lifestyle behavior and known risk factors, such as vitamin D and smoking, that might have contributed to the increased incidence of MS. A possible role of increased survival in MS needs to be examined further.


Measurement of femtosecond Polarization Mode Dispersion (PMD) using biased p-shifted low-coherence interferometry.
Conventional low-coherence interferometry (LCI) can be employed in the measurement of polarization mode dispersion (PMD) of fiber-optic components and fibers. However, the smallest PMD, which can be measured using this technique, is limited by the coherence length of the source. We propose a biased p-shifted Michelson interferometer where a birefringent crystal is inserted in front of the interferometer to introduce a bias differential group delay (DGD) larger than the coherence time of the source. In this way, the limitation imposed by the source coherence time has been overcome and PMDs much smaller than the source coherence time, in the order of several femtoseconds, can be measured. Experimental results for the PMD have been shown and compared with Jones matrix eigen-analysis. The theoretical model confirms the experimental observations.


WormBase 2007.
WormBase (www.wormbase.org) is the major publicly available database of information about Caenorhabditis elegans, an important system for basic biological and biomedical research. Derived from the initial ACeDB database of C. elegans genetic and sequence information, WormBase now includes the genomic, anatomical and functional information about C. elegans, other Caenorhabditis species and other nematodes. As such, it is a crucial resource not only for C. elegans biologists but the larger biomedical and bioinformatics communities. Coverage of core areas of C. elegans biology will allow the biomedical community to make full use of the results of intensive molecular genetic analysis and functional genomic studies of this organism. Improved search and display tools, wider cross-species comparisons and extended ontologies are some of the features that will help scientists extend their research and take advantage of other nematode species genome sequences.


Core-shell materials bearing iron(ii) carbonyl units and their CO-release via an upconversion process.
CO-release induced by near infrared (NIR) light, to which body tissues are relatively transparent, from photoactive CO-releasing molecules (PhotoCORMs) has great significance in exploring the clinical potential of CO. In this work, a novel upconversion nanoparticle-based nanoplatform, UCNPs@SiO2-CORMs, has been developed using a one-pot reaction. The materials liberate CO under the irradiation of NIR light. TEM images of the materials showed that this nanoplatform consisted of a core-shell structure. On the surface were incorporated thiol groups through which mono-iron(ii) carbonyl units, "Fe(η5-Cp)(CO)2" were successfully anchored by a ligand exchange reaction between [Fe(η5-Cp)(CO)2I] (1) and the thiol groups. The core of the materials consists of β-NaYF4:Yb3+/Er3+ upconversion nanoparticles (UCNPs). Strong emission bands around 530 and 550 nm from the materials upon irradiation by NIR fall into the broad band of the electronic spectrum of the materials. Consequently, the constructed nanoplatform steadily released CO upon irradiation with a 980 nm laser (1 W cm-2). Kinetic analysis suggests that CO-release from UCNPs@SiO2-CORMs in DMSO/D2O media fits a zero-order reaction model. Assessment of the cytotoxicity of UCNPs@SiO2-CORMs indicated that they showed excellent biocompatibility and no significant photo-toxicity.


Follow-up of a major psychosis linkage site in 13q13-q14 reveals significant association in both case-control and family samples.
We previously reported a genome-wide significant linkage for major psychosis in chromosome 13q13-q14. An association analysis was conducted in 247 unrelated DSM-IV schizophrenia (SZ) patients and 250 unrelated control subjects from the Eastern Quebec population genotyped with 2150 single nucleotide polymorphisms in 13q13-q14. We also used the kindred sample where linkage was detected (125 SZ, 120 bipolar disorder [BD] and 36 schizoaffective disorder patients vs. 467 unaffected adult relatives) for replication. An association of the T allele of rs1156026 found in the case-control sample (odds ratio [OR] = 1.81, p = 4 × 10(-6), false discovery rate = .01) was replicated in the kindred sample (OR = 1.54, p = .01), strengthening the overall association evidence (p = 8 × 10(-7)). The effect size increased in the subset of unrelated patients with a family history (OR = 2.28) and in the 15 families where SZ was predominant (OR = 2.03). In the kindred sample, onset of either SZ or BD was, on average, 5 years earlier for T/T compared with C/C homozygotes, leading to stronger association in patients with onset before 26 years of age (SZ: OR = 2.40, p = 1.3 × 10(-4); SZ, BD, and schizoaffective disorder combined: OR = 1.87, p = 8 × 10(-5)). Case-control and family-based association provided evidence of a locus at 13q13-q14 related to SZ. The proximity of the associated single nucleotide polymorphism with the linkage signal and the extension of the associated phenotype to major psychosis with younger age of onset indicate congruence between the linkage and association signals. The rs1156026 association is novel and factors explaining its nondetection in previous studies are discussed.


Cytokine and chemokine transcription profile during Mycoplasma pulmonis infection in susceptible and resistant strains of mice: macrophage inflammatory protein 1beta (CCL4) and monocyte chemoattractant protein 2 (CCL8) and accumulation of CCR5+ Th cells.
The progression of murine mycoplasma pneumonia is dependent on T cells and other immune cells. The role of cytokines in immunity are complex, and identifying the network of cytokines produced after infection of mice is essential in dissecting the key cytokine cascades involved mycoplasma disease pathogenesis. In the present study, mRNA expression of 143 different cytokines, chemokines, or receptors were evaluated in lung tissues from both susceptible (BALB/c and C3H/HeN) and resistant (C57BL/6) mice after Mycoplasma pulmonis infection. To accomplish this, membrane-based cDNA microarrays were used to monitor changes mRNA expression in lungs. There was a clear association with disease susceptibility and development of cytokine mRNA expression. In addition to proinflammatory cytokines, mRNA expression of an anti-inflammatory cytokine, interleukin-10, increased with disease severity, suggesting an attempt to moderate the severity of the inflammatory response. Furthermore, it is clear that an array of chemokines produced in susceptible mice could contribute to the recruitment and maintenance of inflammatory cells at the site of disease. In support of this, there was an increase in macrophage inflammatory protein 1beta (MIP-1beta; CCL4) and monocyte chemoattractant protein 2 (MCP-2; CCL8) mRNA levels from mycoplasma-infected mice and a corresponding accumulation of CD4+ Th cells expressing the MIP-1beta/MCP-2 receptor, CCR5, in the lungs of mice. Furthermore, MIP-1beta- and MCP-2-producing cells and CD4+ T cells were found to be in close association in pulmonary lesions. Thus, there was a significant cytokine response associated with disease pathogenesis, and these studies provide important leads and insights into ongoing cytokine- and chemokine-mediated processes in this persistent inflammatory disease.


Testosterone replacement therapy and the heart: friend, foe or bystander?
The role of testosterone therapy (TTh) in cardiovascular disease (CVD) outcomes is still controversial, and it seems will remain inconclusive for the moment. An extensive body of literature has investigated the association of endogenous testosterone and use of TTh with CVD events including several meta-analyses. In some instances, a number of studies reported beneficial effects of TTh on CVD events and in other instances the body of literature reported detrimental effects or no effects at all. Yet, no review article has scrutinized this body of literature using the magnitude of associations and statistical significance reported from this relationship. We critically reviewed the previous and emerging body of literature that investigated the association of endogenous testosterone and use of TTh with CVD events (only fatal and nonfatal). These studies were divided into three groups, "beneficial (friendly use)", "detrimental (foe)" and "no effects at all (bystander)", based on their magnitude of associations and statistical significance from original research studies and meta-analyses of epidemiological studies and of randomized controlled trials (RCT's). In this review article, the studies reporting a significant association of high levels of testosterone with a reduced risk of CVD events in original prospective studies and meta-analyses of cross-sectional and prospective studies seems to be more consistent. However, the number of meta-analyses of RCT's does not provide a clear picture after we divided it into the beneficial, detrimental or no effects all groups using their magnitudes of association and statistical significance. From this review, we suggest that we need a study or number of studies that have the adequate power, epidemiological, and clinical data to provide a definitive conclusion on whether the effect of TTh on the natural history of CVD is real or not.


Arteriovenous Malformation in a Youth with Atypical Autism Symptoms.
Cerebral arteriovenous malformations (AVMs) present a challenge to diagnose in children with developmental disability, because of the overlap in behavioral symptoms and neurologic manifestations. They have been very rarely reported in conjunction with autism spectrum disorder. This case involves a 13 year old male with a history of autism spectrum disorder and significant behavioral issues diagnosed with a thalamic AVM following lateralizing neurologic symptoms. Despite radiosurgical treatment, hemorrhage followed consequently causing extensive neurologic injury and death. This case emphasizes the need for close follow up and coordination within a medical home for children with developmental disabilities. A multidisciplinary team approach is ideal to allow detection of subtle neurologic changes over time that may be masked as behavioral difficulties.


Complete mechanism of sigma* intramolecular aromatic hydroxylation through O2 activation by a macrocyclic dicopper(I) complex.
The present study reports the first example of a complete and detailed mechanism of intramolecular aromatic hydroxylation through O(2) activation by a hexaazamacrocyclic dicoppper(I) complex, [Cu(I)(2)(H3m)](2+). The reactivity of this complex has been previously studied experimentally, although only the characterization of the final mu-phenoxo-mu-hydroxo [Cu(II)(2)(H3m-O)(mu-OH)](2+) product was possible. In the present theoretical study, we unravel the reaction pathway for the overall intramolecular aromatic hydroxylation, that is, from the initial reaction of O(2) with the dicopper(I) species to the final [Cu(II)(2)(H3m-O)(mu-OH)](2+) product using the B3LYP method. Our results indicate that a Cu(I)Cu(II)-superoxo species is formed first, then the interaction of the O(2) moiety with the second Cu(I) center leads to a mu-eta(2):eta(2)-peroxo-Cu(II)(2) intermediate. This latter species is found to be close in energy with the isomeric bis(mu-oxo) species. The relative stability of these two isomers depends on the method of calculation, and therefore, it has not been possible to reach a definite conclusion about the nature of the active species in this reaction mechanism. Notwithstanding, our B3LYP calculations indicate that it is the mu-eta(2):eta(2)-peroxo species that evolves via an electrophilic sigma* attack involving a concerted peroxide O-O bond cleavage and C-O bond formation to a Wheland-type intermediate. The reaction follows with a proton release assisted by the presence of a second aromatic ring yielding a mu-hydroxo-mu-oxo intermediate species, which, in the final stage of the reaction, rearranges to the product. The proton transfer path points out the possibility to design new systems with improved reactivity by properly placing a second aromatic ring to assist the deprotonation step. The lack of high energy barriers and deep energy wells explains the difficulty to trap intermediates experimentally.


A multi-center randomized trial of buprenorphine-naloxone versus clonidine for opioid detoxification: findings from the National Institute on Drug Abuse Clinical Trials Network.
The clinical effectiveness of buprenorphine-naloxone (bup-nx) and clonidine for opioid detoxification in in-patient and out-patient community treatment programs was investigated in the first studies of the National Institute of Drug Abuse Clinical Trials Network. Diagnostic and Statistical Manual version IV (DSM IV)-diagnosed opioid-dependent individuals seeking short-term treatment were randomly assigned, in a 2 : 1 ratio favoring bup-nx, to a 13-day detoxification using bup-nx or clonidine. A total of 113 in-patients (77 bup-nx, 36 clonidine) and 231 out-patients (157 bup-nx, 74 clonidine) participated. Supportive interventions included appropriate ancillary medications and standard counseling procedures guided by a self-help handbook. The criterion for treatment success was defined as the proportion of participants in each condition who were both retained in the study for the entire duration and provided an opioid-free urine sample on the last day of clinic attendance. Secondary outcome measures included use of ancillary medications, number of side effects reported and withdrawal and craving ratings. A total of 59 of the 77 (77%) in-patients assigned to the bup-nx condition achieved the treatment success criterion compared to eight of the 36 (22%) assigned to clonidine, whereas 46 of the 157 (29%) out-patients assigned to the bup-nx condition achieved the treatment success criterion, compared to four of the 74 (5%) assigned to clonidine. The benefits of bup-nx for opioid detoxification are supported and illustrate important ways in which clinical research can be conducted in community treatment programs.


Structural design approaches for creating fat droplet and starch granule mimetics.
This article focuses on hydrogel-based strategies for creating reduced calorie foods with desirable physicochemical, sensory, and nutritional properties. Initially, the role of fat droplets and starch granules in foods is discussed, and then different methods for fabricating hydrogel beads are reviewed, including phase separation, antisolvent precipitation, injection, and emulsion template methods. Finally, the potential application of hydrogel beads as fat droplet and starch granule replacements is discussed. There is still a need for large-scale, high-throughout, and economical methods of fabricating hydrogel beads suitable for utilization within the food industry.


Facile preparation of ammonium alginate-derived nanofibers carrying diverse therapeutic cargo.
Alginic acid was converted to a variety of ammonium alginate derivatives carrying diverse chemical cargo such as analgesics, antibiotics, and enzymes. These functional polymers could be fashioned into nanofibrous mats by electrostatic spinning. The therapeutic payload could be released in functional form by a simple ion exchange mechanism. Prospects in wound healing are discussed.


A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study.
Women who are genetically predisposed to ovarian cancer are at very high risk of developing this disease. Although risk-reducing salpingo-oophorectomy (RRSO) and various screening regimens are currently recommended to reduce ovarian cancer risk, the optimal management strategy has not been established nor have multiple additional issues been adequately addressed. We developed a collaboration among the Clinical Genetics Branch (National Cancer Institute's Intramural Research Program), the Gynecologic Oncology Group (GOG), and the Cancer Genetics Network to address these issues. This is a prospective, international, two-cohort, nonrandomized study of women at genetic risk of ovarian cancer, who chose either to undergo RRSO or screening, at study enrollment. Primary study objectives include quantifying and comparing ovarian and breast cancer incidence in the two study groups, assessing feasibility and selected performance characteristics of a novel ovarian cancer screening strategy (the Risk of Ovarian Cancer Algorithm), evaluating various aspects of quality of life and nononcologic morbidity related to various interventions in at-risk women, and creating a biospecimen repository for subsequent translational research. Study accrual is complete as of November 2006; 2,605 participants enrolled: 1,030 (40%) into the surgical cohort and 1,575 (60%) into the screening cohort. Five years of prospective follow-up ends in November 2011. Verification of BRCA mutation carrier status is under way, either through patient-provided reports from clinical genetic testing done before enrollment or through research-based genetic testing being conducted as part of the protocol. Patient eligibility is currently under evaluation and baseline, surgical, pathology, and outcome data are still being collected. The study design and selected baseline characteristics of cohort members are summarized. This National Cancer Institute intramural/extramural collaboration will provide invaluable prospectively collected observational data on women at high familial ovarian cancer risk, including substantial numbers of women carrying BRCA1/2 mutations. These data will aid in elucidating the effect of RRSO on breast/ovarian cancer risk and the effects of two management strategies, on quality of life and other issues that may influence patient care, as well as providing preliminary estimates of test specificity and positive predictive value of a novel ovarian cancer screening strategy.


Açai (Euterpe oleracea Mart.) dietary intake affects plasma lipids, apolipoproteins, cholesteryl ester transfer to high-density lipoprotein and redox metabolism: A prospective study in women.
The açai fruit (Euterpe oleracea Martius), which is native to the Brazilian Amazon region, was shown to have high polyphenols and MUFA contents. In this study, we aimed to assess the effects of açai consumption on plasma lipids, apolipoproteins, the transfer of lipids to HDL (which is a relevant HDL function), and some biomarkers of redox metabolism. Forty healthy volunteer women aged 24 ± 3 years consumed 200 g of açai pulp/day for 4 weeks; their clinical variables and blood sample were obtained before and after this period. Açai pulp consumption did not alter anthropometric parameters, systemic arterial pressure, glucose, insulin and total, LDL and HDL cholesterol, triglycerides and apolipoprotein (apo) B, but it did increase the concentration of apo A-I. Açai consumption decreased the ROS, ox-LDL and malondialdehyde while increasing the activity of antioxidative paraoxonase 1. Overall, the total antioxidant capacity (TAC) was increased. Regarding the transfer of plasma lipids to HDL, açai consumption increased the transfer of cholesteryl esters (p = 0.0043) to HDL. Unesterified cholesterol, phospholipids and triglyceride transfers were unaffected. The increase in apo A-I and the cholesteryl ester transfer to HDL after the açai intake period suggests that an improvement in the metabolism of this lipoprotein occurred, and it is well known that HDL is protective against atherosclerosis. Another important finding was the general improvement of the anti-oxidant defences elicited by açai consumption. Our data indicate that açai has favourable actions on plasma HDL metabolism and anti-oxidant defence; therefore açai could have a beneficial overall role against atherosclerosis, and it is a consistently good candidate to consider as a functional food.


Cost-effectiveness of CT angiography and perfusion imaging for delayed cerebral ischemia and vasospasm in aneurysmal subarachnoid hemorrhage.
Delayed cerebral ischemia and vasospasm are significant complications following SAH leading to cerebral infarction, functional disability, and death. In recent years, CTA and CTP have been used to increase the detection of delayed cerebral ischemia and vasospasm. Our aim was to perform comparative-effectiveness and cost-effectiveness analyses evaluating CTA and CTP for delayed cerebral ischemia and vasospasm in aneurysmal SAH from a health care payer perspective. We developed a decision model comparing CTA and CTP with transcranial Doppler sonography for detection of vasospasm and delayed cerebral ischemia in SAH. The clinical pathways were based on the "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage: A Guideline for Healthcare Professionals from the American Heart Association/American Stroke Association" (2012). Outcome health states represented mortality and morbidity according to functional outcomes. Input probabilities of symptoms and serial test results from CTA and CTP, transcranial Doppler ultrasound, and digital subtraction angiography were directly derived from an SAH cohort by using a multinomial logistic regression model. Expected benefits, measured as quality-adjusted life years, and costs, measured in 2012 US dollars, were calculated for each imaging strategy. Univariable, multivariable, and probabilistic sensitivity analyses were performed to determine the independent and combined effect of input parameter uncertainty. The transcranial Doppler ultrasound strategy yielded 13.62 quality-adjusted life years at a cost of $154,719. The CTA and CTP strategy generated 13.89 quality-adjusted life years at a cost of $147,097, resulting in a gain of 0.27 quality-adjusted life years and cost savings of $7622 over the transcranial Doppler ultrasound strategy. Univariable and multivariable sensitivity analyses indicated that results were robust to plausible input parameter uncertainty. Probabilistic sensitivity analysis results yielded 96.8% of iterations in the right lower quadrant, representing higher benefits and lower costs. Our model results suggest that CTA and CTP are the preferred imaging strategy in SAH, compared with transcranial Doppler ultrasound, leading to improved clinical outcomes and lower health care costs.