Inference for covariate-adjusted time-dependent prognostic accuracy measures.

Evaluating the prognostic performance of candidate markers for future disease onset or progression is one of the major goals in medical research. A marker's prognostic performance refers to how well it separates patients at the high or low risk of a future disease state. Often the discriminative performance of a marker is affected by the patient characteristics (covariates). Time-dependent receiver operating characteristic (ROC) curves that ignore the informativeness of the covariates will lead to biased estimates of the accuracy parameters. We propose a time-dependent ROC curve that accounts for the informativeness of the covariates in the case of censored data. We propose inverse probability weighted (IPW) estimators for estimating the proposed accuracy parameters. We investigate the performance of the IPW estimators through simulation studies and real-life data analysis.

Effects of oral probiotic and lactoferrin interventions on iron-zinc homeostasis, oxidant/antioxidant equilibrium and diarrhoea incidence of neonatal piglets.

The objective of this study was to examine the effects of early-life host specific probiotic and lactoferrin (LF) supplementations on diarrhoea incidence, iron (Fe)-zinc (Zn) balance and antioxidant capabilities in serum of neonatal piglets. A total of eight sow litters obtained from parity matched sows were randomly divided into four groups and assigned to one of the four interventions: control (2.0 ml normal saline), bovine lactoferrin (bLF) (100 mg bLF in normal saline), probiotic (Pb) (1×109 cfu of swine origin Pediococcus acidilactici FT28 strain) and bLF+Pb (both 100 mg bLF and 1×109 cfu of P. acidilactici FT28). All the piglets received supplementations once daily orally for first 7 days of life. The incidence of diarrhoea markedly decreased in bLF group compared to control group. Notably, no incidences of diarrhoea were recorded in Pb and bLF+Pb groups. The Zn and Fe concentrations were significantly increased from day 7 to 21 in bLF and on day 21 in bLF+Pb group. No such changes were noted in Pb group. Total antioxidant capacity (TAC) in serum was significantly increased on days 7 and 15 in bLF group and on days 7 and 21 in bLF+Pb group. Malonaldehyde concentration was markedly reduced from day 7 to 21 in bLF and bLF+Pb groups. The concentrations of nitrate on days 15 and 21 and malonaldehyde on day 7 were significantly higher in Pb group, but mean TAC was unaltered from day 0 to 21. Although no correlation between the incidence of diarrhoea and Zn/Fe and oxidant/antioxidant homeostasis was noted in the Pb group, the supplementation of P. acidilactici FT28 alone was sufficient to prevent the incidence of diarrhoea in neonatal piglets. Taken together, it is concluded that strategic supplementation of P. acidilactici FT28 in early life could help in preventing diarrhoea until weaning of piglets.

Prospective evaluation of the diagnostic potential of LipL32 based latex agglutination test for Bovine leptospirosis.

The Livestock Sector of India plays an important role in livelihood security and socioeconomic development of rural households. Leptospirosis is an important zoonotic disease responsible for septicaemia, interstitial nephritis, jaundice, abortion, reproductive problem in most of the animal species. Reproductive disturbances in bovine population is most often restricted to investigation of brucellosis, however apart from brucellosis, there are many undiagnosed diseases like leptospirosis that takes a toll in the reproductive anomalies of cattle and buffalo. Hence, the present study was elucidated to screen the seroprevalence of Leptospira in cattle and buffalo in various hamlets of North India using a user friendly screening test i.e. LipL32 latex agglutination test. The overall seropositivity was found to be 26.01% (230/884) in case of bovine in this study and the LipL32 LAT showed a profound sensitivity and specificity with level of 94.97% and 99.53% respectively.

Dynamic thresholds and a summary ROC curve: Assessing prognostic accuracy of longitudinal markers.

Cancer patients, chronic kidney disease patients, and subjects infected with HIV are routinely monitored over time using biomarkers that represent key health status indicators. Furthermore, biomarkers are frequently used to guide initiation of new treatments or to inform changes in intervention strategies. Since key medical decisions can be made on the basis of a longitudinal biomarker, it is important to evaluate the potential accuracy associated with longitudinal monitoring. To characterize the overall accuracy of a time-dependent marker, we introduce a summary ROC curve that displays the overall sensitivity associated with a time-dependent threshold that controls time-varying specificity. The proposed statistical methods are similar to concepts considered in disease screening, yet our methods are novel in choosing a potentially time-dependent threshold to define a positive test, and our methods allow time-specific control of the false-positive rate. The proposed summary ROC curve is a natural averaging of time-dependent incident/dynamic ROC curves and therefore provides a single summary of net error rates that can be achieved in the longitudinal setting.

Addressing data privacy in matched studies via virtual pooling.

BACKGROUND: Data confidentiality and shared use of research data are two desirable but sometimes conflicting goals in research with multi-center studies and distributed data. While ideal for straightforward analysis, confidentiality restrictions forbid creation of a single dataset that includes covariate information of all participants. Current approaches such as aggregate data sharing, distributed regression, meta-analysis and score-based methods can have important limitations. METHODS: We propose a novel application of an existing epidemiologic tool, specimen pooling, to enable confidentiality-preserving analysis of data arising from a matched case-control, multi-center design. Instead of pooling specimens prior to assay, we apply the methodology to virtually pool (aggregate) covariates within nodes. Such virtual pooling retains most of the information used in an analysis with individual data and since individual participant data is not shared externally, within-node virtual pooling preserves data confidentiality. We show that aggregated covariate levels can be used in a conditional logistic regression model to estimate individual-level odds ratios of interest. RESULTS: The parameter estimates from the standard conditional logistic regression are compared to the estimates based on a conditional logistic regression model with aggregated data. The parameter estimates are shown to be similar to those without pooling and to have comparable standard errors and confidence interval coverage. CONCLUSIONS: Virtual data pooling can be used to maintain confidentiality of data from multi-center study and can be particularly useful in research with large-scale distributed data.

Creep and flow of glasses: strain response linked to the spatial distribution of dynamical heterogeneities.

Mechanical properties are of central importance to materials sciences, in particular if they depend on external stimuli. Here we investigate the rheological response of amorphous solids, namely colloidal glasses, to external forces. Using confocal microscopy and computer simulations, we establish a quantitative link between the macroscopic creep response and the microscopic single-particle dynamics. We observe dynamical heterogeneities, namely regions of enhanced mobility, which remain localized in the creep regime, but grow for applied stresses leading to steady flow. These different behaviors are also reflected in the average particle dynamics, quantified by the mean squared displacement of the individual particles, and the fraction of active regions. Both microscopic quantities are found to be proportional to the macroscopic strain, despite the non-equilibrium and non-linear conditions during creep and the transient regime prior to steady flow.

Impact of age of rubber (Hevea brasiliensis) plantation on earthworm communities of West Tripura (India).

A comparative analysis of earthworm communities was carried out in the rubber plantations (Hevea brasiliensis) of different age groups in West Tripura to understand the impact of such exotic and monoculture plantation in biodiversity conservation. Earthworm communities were studied on monthly basis over a period of one year (2006-2007) in the 3, 10, 14, 20 and 25 year-old plantations. Among twelve earthworm species collected from the studied sites, six species belonged to Octochaetidae [Eutyphoeus assomensis Stephenson, Eutyphoeus comillahnus Michaelsen, Lennogaster chittagongensis (Stephensen), Octochaetona beatrix Gates, Dichogaster offinis Michaelsen, Lennogaster yeicus (Stephensen)], two species each to Megascolecidae [Metaphire houlleti (Perrier), Konchurio sp. 1] and Moniligastridae [Drowida nepalensis Michaelsen, Drawida papillifer papillifer Stephenson], one species each to Glossoscolecidae [Pontoscolex corethrurus (Muller)] and Ocnerodrilidae [Gordiodrilus elegans Beddard]. Exotic species P corethrurus, M. houlleti and native peregrine species like D. nepolensis and D. papillifer papillifer were distributed in all the age groups of plantation, while other species showed restricted distribution. P. corethrurus contributed more than 60% biomass and 70% density of earthworm communities in rubber plantation. With aging of rubber plantations both the densities and biomasses of earthworms increased. High contents of polyphenol, flavonoid and lignin in the litters of 3 and 10 year-old-rubber plantations through their effects on food intake, probably resulted to low biomass values of earthworms in those age groups of plantation. With further increase in the age of plantations beyond 10 years, polyphenol, flavonoid and lignin contents decreased. Accordingly the biomass of earthworms increased with increase in the age of plantation. Soil moisture increased with increase in the age of plantation and there was a good positive correlation between soil moisture and earthworm biomass (p < 0.01). Density, biomass and dominance of earthworms increased while species diversity, species richness and species evenness of earthworm community were decreased with increase in the age of rubber plantation.

Screening obesity by direct and derived anthropometric indices with evaluation of physical efficiency among female college students of kolkata.

BACKGROUND: The available information regarding the obesity pattern of the undergraduate female students of Kolkata is inadequate, though there are several reports which indicate the complications and/or awful consequences of obesity on female health particularly, during the reproductive years. AIM: The present investigation has thus been carried out to report their present physiological status along with the prevalence of obesity, based on their body mass index (BMI), some direct and derived anthropometric indices, and physical fitness. SUBJECTS AND METHODS: This small-scale cross-sectional study conducted in randomly selected 100 female students of different colleges of Kolkata with the age of 18-22 [mean age 20.4 (2.3)] years. Measurements of body composition included total 24 variables, with thirteen direct and eleven derived anthropometric variables; while physical efficiency parameters were physical fitness index, VO2max, energy expenditure and anaerobic power. The data of the experimental group were compared with those of the control group by t-test, using SPSS v.15.0 and MS-Excel v.2013. RESULTS: Analysis of collected data showed majority of the students have normal range of BMI (67.95%), but, 21.95% of students found to be overweight and 3.84% are obese. They also showed higher fat mass [14.40 (4.11)], but, lower waist-to-hip ratio and conicity index. They were found to have poor to moderate physical fitness [57.60 (3.90)] and higher energy expenditure [5.61 (0.72)]. CONCLUSION: The findings of the present obesity screening reports almost one of four female students (24 out of 100 participants) are overweight/obese, indicated higher body fat distribution and increased propensity of being obese with age. Thus, the overall data along with their low physical fitness points out to health risks among female undergraduates of Kolkata.

Non-parametric estimation of a time-dependent predictive accuracy curve.

A major biomedical goal associated with evaluating a candidate biomarker or developing a predictive model score for event-time outcomes is to accurately distinguish between incident cases from the controls surviving beyond t throughout the entire study period. Extensions of standard binary classification measures like time-dependent sensitivity, specificity, and receiver operating characteristic (ROC) curves have been developed in this context (Heagerty, P. J., and others, 2000. Time-dependent ROC curves for censored survival data and a diagnostic marker. Biometrics 56, 337-344). We propose a direct, non-parametric method to estimate the time-dependent Area under the curve (AUC) which we refer to as the weighted mean rank (WMR) estimator. The proposed estimator performs well relative to the semi-parametric AUC curve estimator of Heagerty and Zheng (2005. Survival model predictive accuracy and ROC curves. Biometrics 61, 92-105). We establish the asymptotic properties of the proposed estimator and show that the accuracy of markers can be compared very simply using the difference in the WMR statistics. Estimators of pointwise standard errors are provided.

Comparative efficacy of rHaa86 and rBm86 against Hyalomma anatolicum anatolicum and Rhipicephalus (Boophilus) microplus.

Hyalomma anatolicum anatolicum and Rhipicephalus (Boophilus) microplus are the most economically important tick species in India and other tropical and subtropical regions of the world and transmit pathogens causing animal and human diseases. We demonstrated that vaccination of animal by rHaa86 could be used for the control of both H. a. anatolicum and R. (B.) microplus infestations. By comparing the efficacy of rHaa86 and rBm86, it was observed that vaccine based on rHaa86 will be more effective in controlling homologous challenge infestations (68·7% against larvae and 45·8% against adults). The results of this trial demonstrated that species-specific antigens are the better choice for vaccine development and could serve as an effective tool for the integrated control of H. a. anatolicum.

Effects of five earthworm species on some physico-chemical properties of soil.

An incubation experiment was conducted to study the changes that occur in organic carbon content, phosphorous and potassium availability and other soil properties with ingestion of soil mixed with rubber leaf litter and cow dung by five earthworm species viz. Pontoscolex corethrurus, Drawida assamensis, Drawida papillifer papillifer, Eutyphoeus comillahnus and Metaphire houlletiof rubber plantation in Tripura (India). Due to earthworm activity organic C (1.56-1.63%) and available P (14.71-27.60 mg 100 g(-1)) and K (43.50-49.0 mg 100 g(-1)) content of the soil increased significantly (p < 0.05) in most of the earthworm species studied. M. houlleti and D. papillifer papillifer had the highest P (27.60 mg 100 g ) and K (49.0 mg 100 g ) mobilization capacity, respectively. Earthworms, irrespective of the species, increased the pH (7.05-7.17) and electrical conductivity (663-1383 microS cm(-1)) of the soil significantly (p < 0.05).

SEMEDS: an important tool for air pollution bio-monitoring.

Plant canopies act as absorbers of air-borne dust particles. Characterization of the dusts present over the leaf surfaces can indicate the nature of contaminant present in the surrounding area and possible sources as well. Dust particulates get adsorbed on both the surfaces of leaves, however more dust particulates get deposited on the upper surface. These dusts contain many inorganic elements, which were analyzed in the present study. For the present investigation, SEMEDS technique used to characterize the dusts adsorbed over the leaf surfaces. Using SEMEDS the samples were analyzed by two types of methods i.e. point analysis and elemental mapping. Both the methods showed the presence of elements like Si, Al, Fe, Mg, and Ca in the dusts adsorbed over the leaf surfaces. Thus, SEMEDS can be used for in situ air pollution monitoring using tree leaves from the area concerned.

Visual outcomes following Artisan aphakia iris claw lens implantation.

OBJECTIVE: To assess the visual outcome of eyes undergoing Artisan lens implantation for aphakia, to identify reasons for poor outcomes, and to report incidences of post-operative uveitis, glaucoma, or hyphaema. METHODS: A retrospective analysis of 32 eyes rendered aphakic through various causes, which subsequently underwent Artisan lens implantation. RESULTS: A total of 32 eyes from 31 patients were reviewed. Follow-up ranged from 6 to 42 months, mean 17.3 months. The commonest cause of aphakia was following complicated phacoemulsification in 17 of the 32 eyes (53.1%). At final follow-up, 21 of the 32 eyes (65.6%) achieved best-corrected visual acuity (BCVA) better than that measured pre-operatively and 10 of the 32 eyes (31.3%) matched their pre-operative BCVA. Of 33 eyes, only 1 (0.03%) attained a final BCVA worse than pre-operatively, owing to non-arteritic anterior ischaemic optic neuropathy. A total of 4 of the 33 eyes (12.5%) had pre-existing glaucoma or ocular hypertension; no additional intraocular pressure problems were identified during the follow-up period. CONCLUSION: This study suggests that Artisan iris claw lens insertion is beneficial in acquired aphakia, matching or exceeding pre-operative BCVA in the overwhelming majority of the cases. In addition, this series did not identify any post-operative problems with uveitis, glaucoma, or hyphaema.

Community structure of earthworms under rubber plantations and mixed forests in Tripura, India.

Studies on community structures of earthworms of rubber (Hevea brasiliensis) plantations and their adjacent mixed forests in West Tripura (India) revealed that both the studied sites harvoured 10 earthworm species. Nine species (Pontoscolex corethrurus, Kanchuria sp 1, Metaphire houlleti, Drawida papillifer papillifer, Drawida assamensis, Gordiodrilus elegans, Eutyphoeus assamensis, Eutyphoeus comillahnus and Eutyphoeus gigas) were common to both. While Octochaetona beatrixwas found only in the rubber plantations, Dichogaster affinis was restricted to the mixed forest only. Earthworms were found mostly within 15 cm depth of soils having mean temperature of 27 degrees C, moisture of 23%, pH of 4.57, organic matter of 1.34% and water holding capacity of 36%. Mean earthworm density in rubber plantations (115 ind. m(-2)) was significantly higher (p = 0.003, t = 3.83) than that in the mixed forests (69 ind. m(-2)) due to dominance of Pontoscolex corethrurus, an exotic species. Numbers of dominant species were two (P. corethrurus and D. assamensis) in the rubber plantations and five (P. corethrurus D. assamensis, D. papilliferpapillifer, M. houlleti and Kanchuria sp 1) in the mixed forests. Compared to the mixed forests, significantly low (p<0.05) Shannon diversity index (H) and species evenness and high index of dominance in the rubber plantation were evaluated.

In utero exposure to maternal smoking and women's risk of fetal loss in the Norwegian Mother and Child Cohort (MoBa).

BACKGROUND: Whether in utero exposure to tobacco smoke increases a woman's risk of fetal loss later in life is unknown, though data on childhood exposure suggest an association may exist. This study evaluated the association between in utero exposure to tobacco smoke and fetal loss in the Norwegian Mother and Child Cohort Study (MoBa), which enrolled ∼40% of the pregnant women in Norway from 1999 to 2008. METHODS: Information on exposure to tobacco smoke in utero, the woman's own smoking behavior during pregnancy and other factors was obtained by a questionnaire completed at ∼17 weeks of gestation. Subsequent late miscarriage (fetal death <20 weeks) and stillbirth (fetal death ≥ 20 weeks) were ascertained from the Norwegian Medical Birth Registry. This analysis included 76 357 pregnancies (MoBa data set version 4.301) delivered by the end of 2008; 59 late miscarriages and 270 stillbirths occurred. Cox proportional hazards models were fit for each outcome and for all fetal deaths combined. RESULTS: The adjusted hazard ratio (HR) of late miscarriage was 1.23 [95% confidence interval (CI), 0.72-2.12] in women with exposure to maternal tobacco smoke in utero when compared with non-exposed women. The corresponding adjusted HR for stillbirths was 1.11 (95% CI, 0.85-1.44) and for all fetal deaths combined, it was 1.12 (95% CI, 0.89-1.43). CONCLUSIONS: The relatively wide CI around the HR for miscarriage reflected the limited power to detect an association, due to enrollment around 17 weeks of gestation. However, for in utero exposure to tobacco smoke and risk of stillbirth later in life, where the study power was adequate, our data provided little support for an association.

Efficacy of rHaa86, an orthologue of Bm86, against challenge infestations of Hyalomma anatolicum anatolicum.

In an attempt to develop vaccine against Hyalomma anatolicum anatolicum, the protective efficacy of rHaa86 was evaluated against experimental challenge infestations of homologous tick species and lethal dose of Theileria annulata. Following challenge, a significant difference of 20.9% (P < 0.01) in the dropping per cent of ticks fed on immunized and control animals was recorded. A statistically significant reduction of 49.6 mg (P < 0.01) in the weight of ticks fed on immunized animals in comparison with control was noted. The ticks dropped from immunized animals laid fewer eggs and a reduction of 68.1 mg (P < 0.05) in comparison with the ticks fed on control animals was noted. The DT%, DO%, DR% and E% were calculated as 73.8, 31.3, 15.8 and 82.3% respectively. In all the calves fever (rectal temperature

Formation of nanocrystalline diamond in polymer like carbon films deposited by plasma CVD.

Conventional plasma enhanced chemical vapour deposition (PECVD) method is generally not suitable for the growth of nanocrystalline diamond (NCD) films. However, our study shows that conditions favourable for powder formation help to grow large amount of nanocrystallites in conventional PECVD. With CH4 as the carbon source gas, dilution with Ar and moderate (50 W) rf power enhances formations of powders (nanoparticles) and C2 dimers within the plasma. On the other hand, with pure CH4 or with hydrogen diluted CH4, powder formation as also NCD growth is hindered. It is proposed that the nanoparticles formed in the plasma act as the "islands" while the C2 dimers are the "seeds" for the NCD growth. The structure of the films deposited on the grounded anode under different conditions of dilution has been studied. It is observed that with high Ar dilution the films contain NCD embedded in polymer like carbon (PLC) matrix.

Escheriosomes entrapped DNA vaccine co-expressing Cu-Zn superoxide dismutase and IL-18 confers protection against Brucella abortus.

In the present study, we evaluated prophylactic prospective of liposome based DNA vaccine co-expressing Cu-Zn superoxide dismutase (SOD) along with interleukin-18 (IL-18) against experimental murine brucellosis. The immunization schedule involves liposome-mediated delivery of pVsod (encoding SOD of Brucella abortus) and pVIL18-sod (encoding IL-18 of mouse and SOD of B. abortus) DNA constructs. The data highlight potential of Escherichia coli lipid liposome (escheriosome) based DNA delivery vehicle to induce SOD specific humoral and cellular immune responses in the immunized mice. The co-expression of SOD along with IL-18 ensued in higher lymphoproliferative response and IFN-gamma production in comparison to the group of animals that were immunized with free form of SOD-DNA. Antibody response developed upon immunization with both DNA vaccines was of IgG2a type mainly. The results of the present study show that co-expression of IL-18 along with SOD polarized the antigen specific immune responses toward Th-1 direction, a desirable feature to control intracellular pathogens.

Molecular characterization of avian strains of Pasteurella multocida serogroup-A:1 based on amplification of repetitive regions by PCR.

Repetitive extragenic palindromic (REP)-PCR (polymerase chain reaction), enterobacterial repetitive intergenic consensus (ERIC)-PCR, and single primer PCR assays were employed to characterize 66 strains of Pasteurella multocida serogroup A:1 isolated from avian species belonging to different regions of India. REP-PCR resulted in amplification of REP sequences from the genome which were in the range of approximately 200 to approximately 3000 bp and accounted for a total of 54 distinguishing profiles (D=0.99). ERIC-PCR analysis also generated amplified products in the range of approximately 200 to approximately 3200 bp categorizing strains into a total of 50 different profiles (D=0.98). Amplification of repetitive regions using a microsatellite primer (GTG)(5), resulted in clear distinctive bands ranging from approximately 200 to approximately 2400 bp. Strains were assigned to 43 profiles (D=0.96). No correlation could be drawn between genotypic profiles and avian hosts with their geographical area of origin. Avian strains of P. multocida serogroup A:1 were found to be highly heterogeneous with diverse profiles. REP-PCR was found to be highly discriminatory and simple method for differentiation of phenotypically similar strains. The present study also indicated that PCR based amplification of repetitive regions of P. multocida is a rapid technique with good discrimination and could be employed directly for routine typing of field isolates from fowl cholera outbreaks.

Escheriosome-mediated delivery of recombinant ribosomal L7/L12 protein confers protection against murine brucellosis.

Brucellosis is an important zoonotic disease that causes abortion in cattle and undulant fever, arthritis, endocarditis and meningitis in human. In spite of the fact that immunization could be an efficient measure to control brucellosis, not a single ideal vaccine against this important disease has been developed so far. In order to develop an effective vaccine against Brucella abortus (B. abortus), various protective immunodominant gene/protein products of the pathogen have been studied in combination with different adjuvants. For example, recombinant ribosomal protein L7/L12 (rL7/L12) although an interesting T-cell antigen, normally failed to evoke protective immune response when used in free form. In the present study we have demonstrated that Escherischia coli (E. coli) lipid liposome (escheriosome)-mediated cytosolic delivery of recombinant rL7/L12 protein can elicit strong immunological responses in the Balb/c mice. In contrast, egg PC/Chol liposome entrapped rL7/L12, in a manner similar to its free form, was found to impart relatively poor immune response. Furthermore, escheriosome entrapped rL7/L12 protein elicited high IgG2a isotype response suggestive of its relevance in imparting protection against brucellosis in mice. Altogether the present study is a clear indicative of the possible use of escheriosome-based delivery of rL7/L12 protein to induce protective immune responses against experimental murine brucellosis.