Competing risks analysis for neutrophil to lymphocyte ratio as a predictor of diabetic retinopathy incidence in the Scottish population

Background Diabetic retinopathy (DR) is a major sight-threatening microvascular complication in individuals with diabetes. Systemic inflammation combined with oxidative stress is thought to capture most of the complexities involved in the pathology of diabetic retinopathy. A high level of neutrophil–lymphocyte ratio (NLR) is an indicator of abnormal immune system activity. Current estimates of the association of NLR with diabetes and its complications are almost entirely derived from cross-sectional studies, suggesting that the nature of the reported association may be more diagnostic than prognostic. Therefore, in the present study, we examined the utility of NLR as a biomarker to predict the incidence of DR in the Scottish population. Methods The incidence of DR was defined as the time to the first diagnosis of R1 or above grade in the Scottish retinopathy grading scheme from type 2 diabetes diagnosis. The effect of NLR and its interactions were explored using a competing risks survival model adjusting for other risk factors and accounting for deaths. The Fine and Gray subdistribution hazard model (FGR) was used to predict the effect of NLR on the incidence of DR. Results We analysed data from 23,531 individuals with complete covariate information. At 10 years, 8416 (35.8%) had developed DR and 2989 (12.7%) were lost to competing events (death) without developing DR and 12,126 individuals did not have DR. The median (interquartile range) level of NLR was 2.04 (1.5 to 2.7). The optimal NLR cut-off value to predict retinopathy incidence was 3.04. After accounting for competing risks at 10 years, the cumulative incidence of DR and deaths without DR were 50.7% and 21.9%, respectively. NLR was associated with incident DR in both Cause-specific hazard (CSH = 1.63; 95% CI: 1.28–2.07) and FGR models the subdistribution hazard (sHR = 2.24; 95% CI: 1.70–2.94). Both age and HbA1c were found to modulate the association between NLR and the risk of DR. Conclusions The current study suggests that NLR has a promising potential to predict DR incidence in the Scottish population, especially in individuals less than 65 years and in those with well-controlled glycaemic status

Elastic and anelastic relaxation behaviour of perovskite multiferroics II: PbZr0.53_{0.53}Ti0.47_{0.47}O3_3 (PZT)–PbFe0.5_{0.5}Ta0.5_{0.5}O3_3 (PFT)

Elastic and anelastic properties of ceramic samples of multiferroic perovskites with nominal compositions across the binary join PbZr$_{0.53}$Ti$_{0.47}$O$_3$–PbFe$_{0.5}$Ta$_{0.5}$O$_3$ (PZT–PFT) have been assembled to create a binary phase diagram and to address the role of strain relaxation associated with their phase transitions. Structural relationships are similar to those observed previously for PbZr$_{0.53}$Ti$_{0.47}$O$_3$–PbFe$_{0.5}$Nb$_{0.5}$O$_3$ (PZT–PFN), but the magnitude of the tetragonal shear strain associated with the ferroelectric order parameter appears to be much smaller. This leads to relaxor character for the development of ferroelectric properties in the end member PbFe$_{0.5}$Ta$_{0.5}$O$_3$. As for PZT–PFN, there appear to be two discrete instabilities rather than simply a reorientation of the electric dipole in the transition sequence cubic–tetragonal–monoclinic, and the second transition has characteristics typical of an improper ferroelastic. At intermediate compositions, the ferroelastic microstructure has strain heterogeneities on a mesoscopic length scale and, probably, also on a microscopic scale. This results in a wide anelastic freezing interval for strain-related defects rather than the freezing of discrete twin walls that would occur in a conventional ferroelastic material. In PFT, however, the acoustic loss behaviour more nearly resembles that due to freezing of conventional ferroelastic twin walls. Precursor softening of the shear modulus in both PFT and PFN does not fit with a Vogel–Fulcher description, but in PFT there is a temperature interval where the softening conforms to a power law suggestive of the role of fluctuations of the order parameter with dispersion along one branch of the Brillouin zone. Magnetic ordering appears to be coupled only weakly with a volume strain and not with shear strain but, as with multiferroic PZT–PFN perovskites, takes place within crystals which have significant strain heterogeneities on different length scales.RUS facilities in Cambridge were established with funding from the Natural Environment Research Council (Grants NE/B505738/1, NE/F017081/1). The present work was supported by Grant No. EP/ I036079/1 from the Engineering and Physical Sciences Research Council. We thank Dr. Sam Crossley for his assistance with dielectric analysis and the use of his software to run those measurements. JAS gratefully acknowledges the hospitality of the Max Planck Institute for Chemical Physics of Solids. The Nanopaleomagnetism lab has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP/2007– 2013)/ERC Grant Agreement 320750. SED and HS acknowledge support from the Winton Programme for the physics of sustainability. HS also acknowledges support from the Funai Foundation for Information Technology and the British Council Japan Association. Part of the work was carried out at the University of Puerto Rico, supported by the DOEEBSCoR project DEG02-ER46526

HIV Testing among Patients with Presumptive Tuberculosis: How Do We Implement in a Routine Programmatic Setting? Results of a Large Operational Research from India.

BACKGROUND: In March 2012, World Health Organization recommended that HIV testing should be offered to all patients with presumptive TB (previously called TB suspects). How this is best implemented and monitored in routine health care settings in India was not known. An operational research was conducted in Karnataka State (South India, population 64 million, accounts for 10% of India's HIV burden), to test processes and learn results and challenges of screening presumptive TB patients for HIV within routine health care settings. METHODS: In this cross-sectional study conducted between January-March 2012, all presumptive TB patients attending public sector sputum microscopy centres state-wide were offered HIV testing by the laboratory technician, and referred to the nearest public sector HIV counselling and testing services, usually within the same facility. The HIV status of the patients was recorded in the routine TB laboratory form and TB laboratory register. The laboratory register was compiled to obtain the number of presumptive TB patients whose HIV status was ascertained, and the number found HIV positive. Aggregate data on reasons for non-testing were compiled at district level. RESULTS: Overall, 115,308 patients with presumptive TB were examined for sputum smear microscopy at 645 microscopy centres state-wide. Of these, HIV status was ascertained for 62,847(55%) among whom 7,559(12%) were HIV-positive, and of these, 3,034(40%) were newly diagnosed. Reasons for non-testing were reported for 37,700(72%) of the 52,461 patients without HIV testing; non-availability of testing services at site of sputum collection was cited by health staff in 54% of respondents. Only 4% of patients opted out of HIV testing. CONCLUSION: Offering HIV testing routinely to presumptive TB patients detected large numbers of previously-undetected instances of HIV infection. Several operational challenges were noted which provide useful lessons for improving uptake of HIV testing in this important group

Clinical and cost effectiveness of memory rehabilitation following traumatic brain injury: a pragmatic cluster randomized controlled trial

OBJECTIVE:To evaluate the clinical and cost effectiveness of a group-based memory rehabilitation programme for people with traumatic brain injury.DESIGN:Multicentre, pragmatic, observer-blinded, randomized controlled trial in England.SETTING:Community.PARTICIPANTS:People with memory problems following traumatic brain injury, aged 18-69 years, able to travel to group sessions, communicate in English, and give consent.INTERVENTIONS:A total of 10 weekly group sessions of manualized memory rehabilitation plus usual care (intervention) vs. usual care alone (control).MAIN MEASURES:The primary outcome was the patient-reported Everyday Memory Questionnaire (EMQ-p) at six months post randomization. Secondary outcomes were assessed at 6 and 12 months post randomization.RESULTS:We randomized 328 participants. There were no clinically important differences in the primary outcome between arms at six-month follow-up (mean EMQ-p score: 38.8 (SD 26.1) in intervention and 44.1 (SD 24.6) in control arms, adjusted difference in means: -2.1, 95% confidence interval (CI): -6.7 to 2.5, p = 0.37) or 12-month follow-up. Objectively assessed memory ability favoured the memory rehabilitation arm at the 6-month, but not at the 12-month outcome. There were no between-arm differences in mood, experience of brain injury, or relative/friend assessment of patient's everyday memory outcomes, but goal attainment scores favoured the memory rehabilitation arm at both outcome time points. Health economic analyses suggested that the intervention was unlikely to be cost effective. No safety concerns were raised.CONCLUSION:This memory rehabilitation programme did not lead to reduced forgetting in daily life for a heterogeneous sample of people with traumatic brain injury. Further research will need to examine who benefits most from such interventions

Weak localization in Electric-double-layer gated Few-layer graphene

We induce surface carrier densities up to $\sim7\cdot 10^{14}$cm$^{-2}$ in few-layer graphene devices by electric double layer gating with a polymeric electrolyte. In 3-, 4- and 5-layer graphene below 20-30K we observe a logarithmic upturn of resistance that we attribute to weak localization in the diffusive regime. By studying this effect as a function of carrier density and with ab-initio calculations we derive the dependence of transport, intervalley and phase coherence scattering lifetimes on total carrier density. We find that electron-electron scattering in the Nyquist regime is the main source of dephasing at temperatures lower than 30K in the $\sim10^{13}$cm$^{-2}$ to $\sim7 \cdot 10^{14}$cm$^{-2}$ range of carrier densities. With the increase of gate voltage, transport elastic scattering is dominated by the competing effects due to the increase in both carrier density and charged scattering centers at the surface. We also tune our devices into a crossover regime between weak and strong localization, indicating that simultaneous tunability of both carrier and defect density at the surface of electric double layer gated materials is possible.We acknowledge funding from EU Graphene Flagship, ERC Grant Hetero2D, EPSRC Grant Nos. EP/ 509K01711X/1, EP/K017144/1, EP/N010345/1, EP/M507799/ 5101, and EP/L016087/1 and the Joint Project for the Internationalization of Research 2015 launched by Politecnico di Torino under funding of Compagnia di San Paolo

Solvothermal Synthesis of Ternary Sulfides of Sb2 − xBixS3(x = 0.4, 1) with 3D Flower-Like Architectures

Flower-like nanostructures of Sb2 − xBixS3(x = 0.4, 1.0) were successfully prepared using both antimony diethyldithiocarbamate [Sb(DDTC)3] and bismuth diethyldithiocarbamate [Bi(DDTC)3] as precursors under solvothermal conditions at 180 °C. The prepared Sb2 − xBixS3 with flower-like 3D architectures were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDS), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED). The flower-like architectures, with an average diameter of ~4 μm, were composed of single-crystalline nanorods with orthorhombic structures. The optical absorption properties of the Sb2 − xBixS3 nanostructures were investigated by UV–Visible spectroscopy, and the results indicate that the Sb2 − xBixS3 compounds are semiconducting with direct band gaps of 1.32 and 1.30 eV for x = 0.4 and 1.0, respectively. On the basis of the experimental results, a possible growth mechanism for the flower-like Sb2 − xBixS3 nanostructures is suggested

Source of Previous Treatment for Re-Treatment TB Cases Registered under the National TB Control Programme, India, 2010

BACKGROUND: In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome. OBJECTIVES: To assess the source of previous treatment for re-treatment TB patients registered under India's Revised National TB control Programme (RNTCP). METHODOLOGY: A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought. RESULTS: Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 'relapse' cases, 105 'failure' cases, 437 'treatment after default (TAD)' cases and 575 're-treatment others' cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%-49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and 'retreatment others' (59%) were likely to be treated outside the National Programme, when compared to the proportion among 'relapse' (22%) or 'failure' (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme. CONCLUSIONS: Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation

Persisting right-sided chylothorax in a patient with chronic lymphocytic leukemia: a case report

Introduction Chylothorax caused by chronic lymphocytic leukemia is very rare and the best therapeutic approach, especially the role of modern immunochemotherapy, is not yet defined. Case presentation We present the case of a 65-year-old male Caucasian patient with right-sided chylothorax caused by a concomitantly diagnosed chronic lymphocytic leukemia. As first-line treatment four cycles of an immunochemotherapy, consisting of fludarabine, cyclophosphamide and rituximab were administered. In addition, our patient received total parenteral nutrition for the first two weeks of treatment. Despite the very good clinical response of the lymphoma to treatment, the chylothorax persisted and percutaneous radiotherapy of the thoracic duct was applied. However, eight weeks after the radiotherapy the chylothorax still persisted and our patient agreed to a surgical intervention. A ligation of the thoracic duct via a muscle sparing thoracotomy was performed, resulting in a complete cessation of the pleural effusion. Apart from the first two weeks our patient was treated on an out-patient basis for nearly six months. Conclusion In this case of chylothorax caused by chronic lymphocytic leukemia, immunochemotherapy in combination with conservative treatment, and even consecutive radiotherapy, were not able to stop pleural effusion, despite the very good clinical response of the chronic lymphocytic leukemia to treatment. Out-patient management using repetitive thoracocenteses can be safe as bridging until definitive surgical ligation of the thoracic duct

ADAM33, a New Candidate for Psoriasis Susceptibility

Psoriasis is a chronic skin disorder with multifactorial etiology. In a recent study, we reported results of a genome-wide scan on 46 French extended families presenting with plaque psoriasis. In addition to unambiguous linkage to the major susceptibility locus PSORS1 on Chromosome 6p21, we provided evidence for a susceptibility locus on Chromosome 20p13. To follow up this novel psoriasis susceptibility locus we used a family-based association test (FBAT) for an association scan over the 17 Mb candidate region. A total of 85 uncorrelated SNP markers located in 65 genes of the region were initially investigated in the same set of large families used for the genome wide search, which consisted of 295 nuclear families. When positive association was obtained for a SNP, candidate genes nearby were explored more in detail using a denser set of SNPs. Thus, the gene ADAM33 was found to be significantly associated with psoriasis in this family set (The best association was on a 3-SNP haplotype P = 0.00004, based on 1,000,000 permutations). This association was independent of PSORS1. ADAM33 has been previously associated with asthma, which demonstrates that immune system diseases may be controlled by common susceptibility genes with general effects on dermal inflammation and immunity. The identification of ADAM33 as a psoriasis susceptibility gene identified by positional cloning in an outbred population should provide insights into the pathogenesis and natural history of this common disease

Changes in energy expenditure associated with ingestion of high protein, high fat versus high protein, low fat meals among underweight, normal weight, and overweight females

Background: Metabolic rate is known to rise above basal levels after eating, especially following protein consumption. Yet, this postprandial rise in metabolism appears to vary among individuals. This study examined changes in energy expenditure in response to ingestion of a high protein, high fat (HPHF) meal versus an isocaloric high protein, low fat (HPLF) meal in underweight, normal weight, or overweight females (n = 21) aged 19–28 years. Methods: Energy expenditure, measured using indirect calorimetry, was assessed before and every 30 minutes for 3.5 hours following consumption of the meals on two separate occasions. Height and weight were measured using standard techniques. Body composition was measured using bioelectrical impedance analysis. Results: Significant positive correlations were found between body mass index (BMI) and baseline metabolic rate (MR) (r = 0.539; p = 0.017), between body weight and baseline MR (r = 0.567; p = 0.011), between BMI and average total change in MR (r = 0.591; p = 0.008), and between body weight and average total change in MR (r = 0.464; p = 0.045). Metabolic rate (kcal/min) was significantly higher in the overweight group than the normal weight group, which was significantly higher than the underweight group across all times and treatments. However, when metabolic rate was expressed per kg fat free mass (ffm), no significant difference was found in postprandial energy expenditure between the overweight and normal groups. Changes in MR (kcal/min and kcal/min/kg ffm) from the baseline rate did not significantly differ in the underweight (n = 3) or in the overweight subjects (n = 5) following consumption of either meal at any time. Changes in MR (kcal/min and kcal/min/kg ffm) from baseline were significantly higher in normal weight subjects (n = 11) across all times following consumption of the HPHF meal versus the HPLF meal. Conclusion: There is no diet-induced thermogenic advantage between the HPHF and HPLF meals in overweight and underweight subjects. In contrast, in normal weight subjects, ingestion of a HPHF meal significantly increases MR (69.3 kcal/3.5 hr) versus consumption of a HPLF meal and provides a short-term metabolic advantage