CPT and Lorentz-invariance violation

The largest gap in our understanding of nature at the fundamental level is perhaps a unified description of gravity and quantum theory. Although there are currently a variety of theoretical approaches to this question, experimental research in this field is inhibited by the expected Planck-scale suppression of quantum-gravity effects. However, the breakdown of spacetime symmetries has recently been identified as a promising signal in this context: a number of models for underlying physics can accommodate minuscule Lorentz and CPT violation, and such effects are amenable to ultrahigh-precision tests. This presentation will give an overview of the subject. Topics such as motivations, the SME test framework, mechanisms for relativity breakdown, and experimental tests will be reviewed. Emphasis is given to observations involving antimatter.Comment: 6 page

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

Variation in the use of chemotherapy in lung cancer

Factors influencing the use of chemotherapy for the initial (6 months) treatment of lung cancer in South East England were investigated. The variables explored as possibly influencing the use of chemotherapy were sex, age, the year of diagnosis, the type of lung cancer, the stage, the index of multiple deprivation and the cancer network of residence. χ2 analysis and multivariate logistic regression models were used to examine the effect of each of the variables on the use of chemotherapy. The results showed a highly significant trend in use of chemotherapy over time; the adjusted proportion of patients receiving chemotherapy increasing from 13.6% in 1994 to 29.3% in 2003. However, age, cancer network and type of lung cancer had the strongest influence on the use of chemotherapy. This finding is important when we consider that the NHS Cancer Plan aims at improving inequalities in cancer care in the UK

Improved Adaptive Group Testing Algorithms with Applications to Multiple Access Channels and Dead Sensor Diagnosis

We study group-testing algorithms for resolving broadcast conflicts on a multiple access channel (MAC) and for identifying the dead sensors in a mobile ad hoc wireless network. In group-testing algorithms, we are asked to identify all the defective items in a set of items when we can test arbitrary subsets of items. In the standard group-testing problem, the result of a test is binary--the tested subset either contains defective items or not. In the more generalized versions we study in this paper, the result of each test is non-binary. For example, it may indicate whether the number of defective items contained in the tested subset is zero, one, or at least two. We give adaptive algorithms that are provably more efficient than previous group testing algorithms. We also show how our algorithms can be applied to solve conflict resolution on a MAC and dead sensor diagnosis. Dead sensor diagnosis poses an interesting challenge compared to MAC resolution, because dead sensors are not locally detectable, nor are they themselves active participants.Comment: Expanded version of a paper appearing in ACM Symposium on Parallelism in Algorithms and Architectures (SPAA), and preliminary version of paper appearing in Journal of Combinatorial Optimizatio

The Long Life of Birds: The Rat-Pigeon Comparison Revisited

The most studied comparison of aging and maximum lifespan potential (MLSP) among endotherms involves the 7-fold longevity difference between rats (MLSP 5y) and pigeons (MLSP 35y). A widely accepted theory explaining MLSP differences between species is the oxidative stress theory, which purports that reactive oxygen species (ROS) produced during mitochondrial respiration damage bio-molecules and eventually lead to the breakdown of regulatory systems and consequent death. Previous rat-pigeon studies compared only aspects of the oxidative stress theory and most concluded that the lower mitochondrial superoxide production of pigeons compared to rats was responsible for their much greater longevity. This conclusion is based mainly on data from one tissue (the heart) using one mitochondrial substrate (succinate). Studies on heart mitochondria using pyruvate as a mitochondrial substrate gave contradictory results. We believe the conclusion that birds produce less mitochondrial superoxide than mammals is unwarranted

Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study

In myelodysplastic syndromes (MDS), health-related quality of life (HRQoL) represents a relevant patient-reported outcome, which is essential in individualized therapy planning. Prospective data on HRQoL in lower-risk MDS remain rare. We assessed HRQOL by EQ-5D questionnaire at initial diagnosis in 1690 consecutive IPSS-Low/Int-1 MDS patients from the European LeukemiaNet Registry. Impairments were compared with age- and sex-matched EuroQol Group norms. A significant proportion of MDS patients reported moderate/severe problems in the dimensions pain/discomfort (49.5%), mobility (41.0%), anxiety/depression (37.9%), and usual activities (36.1%). Limitations in mobility, self-care, usual activities, pain/discomfort, and EQ-VAS were significantly more frequent in the old, in females, and in those with high co-morbidity burden, low haemoglobin levels, or red blood cells transfusion need (

GABAergic Neuron Deficit As An Idiopathic Generalized Epilepsy Mechanism: The Role Of BRD2 Haploinsufficiency In Juvenile Myoclonic Epilepsy

Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all epilepsies. They have strong, but elusive, genetic components and sex-specific seizure expression. Multiple linkage and population association studies have connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null mutation at the homologous Brd2 locus results in embryonic lethality while heterozygous Brd2+/− mice are viable and overtly normal. However, using the flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/− males have a decreased clonic, and females a decreased tonic-clonic, seizure threshold. Additionally, long-term EEG/video recordings captured spontaneous seizures in three out of five recorded Brd2+/− female mice. Anatomical analysis of specific regions of the brain further revealed significant differences in Brd2+/− vs +/+ mice. Specifically, there were decreases in the numbers of GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia pathway, i.e., in the neocortex and striatum of Brd2+/− mice, compared to Brd2+/+ mice. There were also fewer GABAergic neurons in the substantia nigra reticulata (SNR), yet there was a minor, possibly compensatory increase in the GABA producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the superior colliculus and ventral medial thalamic nucleus, the main SNR outputs, was significantly decreased in Brd2+/− mice, further supporting GABA downregulation. Our data show that the non-channel-encoding, developmentally critical Brd2 gene is associated with i) sex-specific increases in seizure susceptibility, ii) the development of spontaneous seizures, and iii) seizure-related anatomical changes in the GABA system, supporting BRD2's involvement in human IGE

Predictors of pneumococcal carriage and the effect of the 13-valent pneumococcal conjugate vaccination in the Western Australian Aboriginal population

Background The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced to prevent invasive pneumococcal disease (IPD) in Western Australian (WA) Aboriginal people in 2001. PCV13 replaced PCV7 in July 2011, covering six additional pneumococcal serotypes; however, IPD rates remained high in Aboriginal people in WA. Upper respiratory tract pneumococcal carriage can precede IPD, and PCVs alter serotype distribution. Methods To assess the impact of PCV13 introduction, identify emerging serotypes, and assess risk factors for carriage, nasopharyngeal swabs and information on demographic characteristics, health, medication and living conditions from Aboriginal children and adults across WA from August 2008 to November 2014 were collected. Bacteria were cultured using selective media and pneumococcal isolates were serotyped by Quellung reaction. Risk factors were analysed by multivariable logistic regression. Results One thousand five hundred swabs pre- and 1385 swabs post-PCV13 introduction were collected. Pneumococcal carriage was detected in 66.8 % of children 53.2 % of 5–14 year-olds post-PCV13, compared with pre-PCV13 prevalence of 72.2 % and 49.4 %, respectively. The prevalence of PCV13-non-PCV7 serotypes decreased in children 13.5 % pre-PCV13 to 5.8 % post-PCV13 (p \u3c 0.01), and from 8.4 % to 6.1 % in children 5–14 years old (p \u3e 0.05). The most common serotypes post-PCV13 were 11A (prevalence 4.0 %), 15B (3.5 %), 16F (3.5 %), and 19F (3.2 %). Risk of detection of pneumococcal carriage increased until age 12 months (odds ratio [OR] 4.19, 95 % confidence interval [CI] 2.39–7.33), with nasal discharge (OR 2.49 [95 % CI 2.00–3.09]), residence in a remote community (OR 2.21 [95 % CI 1.67–2.92]) and household crowding (OR 1.36 [95 % CI 1.11–1.67]). Recent antibiotic use was negatively associated with pneumococcal carriage (OR 0.48 [95 % CI 0.33–0.69]). Complete resistance to penicillin was present among isolates of serotypes 19A (6.0 %), 19F (2.3 %) and non-serotypeable isolates (1.9 %). Serotype 23F and newly emerged serotype 7B isolates showed high rates of resistance to cotrimoxazole, erythromycin and tetracycline (86.9 %, 86.9 %, 82.0 %, respectively for 23F, 100.0 %, 100.0 % and 93.3 % for 7B). Conclusion Since PCV13 replaced PCV7, carriage of PCV13-non-PCV7 serotypes decreased significantly among childrenold, those most likely to have received PCV13, and to a lesser extent in older people. Known risk factors for carriage including crowding and young age remain in the Aboriginal population