Potential benefits of an adaptive forward collision warning system

Forward collision warning (FCW) systems can reduce rear-end vehicle collisions. However, if the presentation of warnings is perceived as mistimed, trust in the system is diminished and drivers become less likely to respond appropriately. In this driving simulator investigation, 45 drivers experienced two FCW systems: a non-adaptive and an adaptive FCW that adjusted the timing of its alarms according to each individual driver’s reaction time. Whilst all drivers benefited in terms of improved safety from both FCW systems, non-aggressive drivers (low sensation seeking, long followers) did not display a preference to the adaptive FCW over its non-adaptive equivalent. Furthermore, there was little evidence to suggest that the non-aggressive drivers’ performance differed with either system. Benefits of the adaptive system were demonstrated for aggressive drivers (high sensation seeking, short followers). Even though both systems reduced their likelihood of a crash to a similar extent, the aggressive drivers rated each FCW more poorly than their non-aggressive contemporaries. However, this group, with their greater risk of involvement in rear-end collisions, reported a preference for the adaptive system as they found it less irritating and stress-inducing. Achieving greater acceptance and hence likely use of a real system is fundamental to good quality FCW design

Trajectories of fatigue in cancer patients during psychological care

Objective Psycho-oncological institutions offer specialized care for cancer patients. Little is known how this care might impact fatigue. This study aimed to identify fatigue trajectories during psychological care, examined factors distinguishing these trajectories and predicted fatigue severity after nine months of psychological care. Design Naturalistic, longitudinal study of 238 cancer patients receiving psycho-oncological care in the Netherlands. Data were collected before initiation of psychological care (T1) and three (T2) and nine months (T3) afterwards. Latent class growth analysis, repeated measure analyses (RMA) and linear regression analysis were performed. Main Outcome Measures Fatigue severity: Checklist Individual Strength. Results Three fatigue trajectories were identified: high- (30%), moderate- (62%) and low-level fatigue (8%). While statistically significant decreases in fatigue were found, this decrease was not clinically relevant. RMA showed main effects for time for fatigue trajectories on depression, anxiety, personal control and illness cognitions. Fatigue severity and physical symptoms at T1, but not demographic or clinical factors, were predictive of fatigue severity at T3. Conclusions Fatigue is very common during psycho-oncological care, and notably not clinically improving. As symptoms of fatigue, depression, anxiety and physical symptoms often cluster, supplementary fatigue treatment should be considered when it is decided to treat other symptoms first

23 Questions of fluency in Australian languages revitalisation

Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion

The Myanmar dairy sector : a quickscan of opportunities

This report describes the Myanmar dairy sector and opportunities for development, for private as well as public actors. It describes the dairy market, dairy farming systems, and the enabling environment for dairy. A number of business opportunities are listed. It concludes with recommendations on dairy clusters, dairy strategy development , and capacity development activities

Optimized whole genome association scanning for discovery of HLA class I-restricted minor histocompatibility antigens

Patients undergoing allogeneic stem cell transplantation as treatment for hematological diseases face the risk of Graft-versus-Host Disease as well as relapse. Graft-versus-Host Disease and the favorable Graft-versus-Leukemia effect are mediated by donor T cells recognizing polymorphic peptides, which are presented on the cell surface by HLA molecules and result from single nucleotide polymorphism alleles that are disparate between patient and donor. Identification of polymorphic HLA-binding peptides, designated minor histocompatibility antigens, has been a laborious procedure, and the number and scope for broad clinical use of these antigens therefore remain limited. Here, we present an optimized whole genome association approach for discovery of HLA class I minor histocompatibility antigens. T cell clones isolated from patients who responded to donor lymphocyte infusions after HLA-matched allogeneic stem cell transplantation were tested against a panel of 191 EBV-transformed B cells, which have been sequenced by the 1000 Genomes Project and selected for expression of seven common HLA class I alleles (HLA-A*01:01, A*02:01, A*03:01, B*07:02, B*08:01, C*07:01, and C*07:02). By including all polymorphisms with minor allele frequencies above 0.01, we demonstrated that the new approach allows direct discovery of minor histocompatibility antigens as exemplified by seven new antigens in eight different HLA class I alleles including one antigen in HLA-A*24:02 and HLA-A*23:01, for which the method has not been originally designed. Our new whole genome association strategy is expected to rapidly augment the repertoire of HLA class I-restricted minor histocompatibility antigens that will become available for donor selection and clinical use to predict, follow or manipulate Graft-versus-Leukemia effect and Graft-versus-Host Disease after allogeneic stem cell transplantation.Development and application of statistical models for medical scientific researc

Characterization of pathogenic SORL1 genetic variants for association with Alzheimer's disease

Accumulating evidence suggests that genetic variants in the SORL1 gene are associated with Alzheimer disease (AD), but a strategy to identify which variants are pathogenic is lacking. In a discovery sample of 115 SORL1 variants detected in 1908 Dutch AD cases and controls, we identified the variant characteristics associated with SORL1 variant pathogenicity. Findings were replicated in an independent sample of 103 SORL1 variants detected in 3193 AD cases and controls. In a combined sample of the discovery and replication samples, comprising 181 unique SORL1 variants, we developed a strategy to classify SORL1 variants into five subtypes ranging from pathogenic to benign. We tested this pathogenicity screen in SORL1 variants reported in two independent published studies. SORL1 variant pathogenicity is defined by the Combined Annotation Dependent Depletion (CADD) score and the minor allele frequency (MAF) reported by the Exome Aggregation Consortium (ExAC) database. Variants predicted strongly damaging (CADD score >30), which are extremely rare (ExAC-MAF <1 × 10 '5) increased AD risk by 12-fold (95% CI 4.2-34.3; P=5 × 10 '9). Protein-truncating SORL1 mutations were all unknown to ExAC and occurred exclusively in AD cases. More common SORL1 variants (ExAC-MAF≥1 × 10 '5) were not associated with increased AD risk, even when predicted strongly damaging. Findings were independent of gender and the APOE-I 4 allele. High-risk SORL1 variants were observed in a substantial proportion of the AD cases analyzed (2%). Based on their effect size, we propose to consider high-risk SORL1 variants next to variants in APOE, PSEN1, PSEN2 and APP for personalized risk assessments in clinical practice

Finite-temperature Fermi-edge singularity in tunneling studied using random telegraph signals

We show that random telegraph signals in metal-oxide-silicon transistors at millikelvin temperatures provide a powerful means of investigating tunneling between a two-dimensional electron gas and a single defect state. The tunneling rate shows a peak when the defect level lines up with the Fermi energy, in excellent agreement with theory of the Fermi-edge singularity at finite temperature. This theory also indicates that defect levels are the origin of the dissipative two-state systems observed previously in similar devices.Comment: 5 pages, REVTEX, 3 postscript figures included with epsfi

Adenoviral vaccines promote protective tissue-resident memory T cell populations against cancer

Background Adenoviral vectors emerged as important platforms for cancer immunotherapy. Vaccination with adenoviral vectors is promising in this respect, however, their specific mechanisms of action are not fully understood. Here, we assessed the development and maintenance of vaccine-induced tumor-specific CD8(+) T cells elicited upon immunization with adenoviral vectors. Methods Adenoviral vaccine vectors encoding the full-length E7 protein from human papilloma virus (HPV) or the immunodominant epitope from E7 were generated, and mice were immunized intravenously with different quantities (10(7), 10(8) or 10(9) infectious units). The magnitude, kinetics and tumor protection capacity of the induced vaccine-specific T cell responses were evaluated. Results The adenoviral vaccines elicited inflationary E7-specific memory CD8(+) T cell responses in a dose-dependent manner. The magnitude of these vaccine-specific CD8(+) T cells in the circulation related to the development of E7-specific CD8(+) tissue-resident memory T (T-RM) cells, which were maintained for months in multiple tissues after vaccination. The vaccine-specific CD8(+) T cell responses conferred long-term protection against HPV-induced carcinomas in the skin and liver, and this protection required the induction and accumulation of CD8(+) T-RM cells. Moreover, the formation of CD8(+) T-RM cells could be enhanced by temporal targeting CD80/CD86 costimulatory interactions via CTLA-4 blockade early after immunization. Conclusions Together, these data show that adenoviral vector-induced CD8(+) T cell inflation promotes protective T-RM cell populations, and this can be enhanced by targeting CTLA-4.Transplantation and autoimmunit

Heritability of the shape of subcortical brain structures in the general population

The volumes of subcortical brain structures are highly heritable, but genetic underpinnings of their shape remain relatively obscure. Here we determine the relative contribution of genetic factors to individual variation in the shape of seven bilateral subcortical structures: the nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen and thalamus. In 3,686 unrelated individuals aged between 45 and 98 years, brain magnetic resonance imaging and genotyping was performed. The maximal heritability of shape varies from 32.7 to 53.3% across the subcortical structures. Genetic contributions to shape extend beyond influences on intracranial volume and the gross volume of the respective structure. The regional variance in heritability was related to the reliability of the measurements, but could not be accounted for by technical factors only. These findings could be replicated in an independent sample of 1,040 twins. Differences in genetic contributions within a single region reveal the value of refined brain maps to appreciate the genetic complexity of brain structures

Excess-noise-enhanced parametric down conversion

We calculate the influence of excess noise on parametric down conversion in an unstable optical parametric oscillator (OPO), using a quantum quasimode description. We find a strongly enhanced pair photon generation rate below threshold as compared to a conventional stable cavity setup of comparable gain and loss. In addition, the oscillation threshold is lowered due to the influence of the excess noise and the squeezing properties of the emitted light are significantly changed. In general, the maximal quantum-noise suppression in one quadrature component is reduced, which poses strong limitations for the practical usefulness of a geometrically unstable OPO source. The analytical results from our quasimode description are in good agreement with numerical simulations using a positive-P representation of the field in mode space and in position space