Adult neurogenesis and pattern separation in rodents: A critical evaluation of data,tasks and interpretation

The ability to discriminate and store similar inputs as distinct representations in memory is thought to rely on a process called pattern separation in the dentate gyrus of the hippocampus. Recent computational and empirical findings support a role for adult-born granule neurons in spatial pattern separation. We reviewed rodent studies that have manipulated both hippocampal adult neurogenesis and assessed pattern separation. The majority of studies report a supporting role of adult born neurons in pattern separation as measured at the behavioral level. However, closer evaluation of the published findings reveals variation in both pattern separation tasks and in the interpretation of behavioral performance that, taken together, suggests that the role of hippocampal adult neurogenesis in pattern separation may be less established than is currently assumed. Assessment of pattern separation at the network level through the use of immediate early gene expression, optogenetic, pharmacogenetic and/or in vivo electrophysiology studies could be instrumental in further confirming a role of adult born neurons in pattern separation further. Finally, hippocampal adult neurogenesis and pattern separation are not an exclusive pair, as evidence for hippocampal adult neurogenesis contributing to the temporal separation of events in memory, forgetting and cognitive flexibility has also been found. We conclude that whereas current empirical evidence for the involvement of hippocampal adult neurogenesis in pattern separation seems supportive, there is a need for careful interpretation of behavioral findings and an integration of the various proposed functions of adult born neurons.     

Incidence of T315I mutation in BCR/ABL-positive CML and ALL patients

Objectives

Targeted therapy of Philadelphia-positive ALL and CML patients using imatinib (IM) has caused significant changes in treatment course and has increased the survival of patients. A small group of patients show resistance to IM. Acquired mutations in tyrosine kinase domain of BCR-ABL protein are a mechanism for development of resistance. T315I is one of the most common acquired mutations in this domain, which occurs in ATP binding site and inhibits the formation of hydrogen bond with IM. The aim of this study was to evaluate the prevalence of this mutation in BCR/ABL-positive CML and ALL patients.

Methods

To conduct this study, 60 BCR-ABL-positive patients (including 50 CML and 10 ALL patients) who were subject to treatment with IM were selected. After taking the samples, presence of T315I mutation was assessed using ARMS-PCR on cDNA and its polymorphism was evaluated by sequencing.

Results

The results showed that among 60 patients, only three patients had T315I mutation, which was detected using ARMS technique. The three patients bearing mutation were afflicted with CML and no significant association was found between blood parameters with duration of treatment in presence of mutation.

Conclusions

The mutation was found in three CML patients, which indicated lower likelihood and diagnostic value of this mutation in ALL patients. Given the negative direct sequencing results in T315I patients, it can be concluded that ARMS-PCR is a more sensitive technique when the number of cancer cells is low in patients during treatment.

     

Classification of motor imagery tasks for BCI with multiresolution analysis and multiobjective feature selection

Background

Brain-computer interfacing (BCI) applications based on the classification of electroencephalographic (EEG) signals require solving high-dimensional pattern classification problems with such a relatively small number of training patterns that curse of dimensionality problems usually arise. Multiresolution analysis (MRA) has useful properties for signal analysis in both temporal and spectral analysis, and has been broadly used in the BCI field. However, MRA usually increases the dimensionality of the input data. Therefore, some approaches to feature selection or feature dimensionality reduction should be considered for improving the performance of the MRA based BCI.

Methods

This paper investigates feature selection in the MRA-based frameworks for BCI. Several wrapper approaches to evolutionary multiobjective feature selection are proposed with different structures of classifiers. They are evaluated by comparing with baseline methods using sparse representation of features or without feature selection.

Results and conclusion

The statistical analysis, by applying the Kolmogorov-Smirnoff and Kruskal–Wallis tests to the means of the Kappa values evaluated by using the test patterns in each approach, has demonstrated some advantages of the proposed approaches. In comparison with the baseline MRA approach used in previous studies, the proposed evolutionary multiobjective feature selection approaches provide similar or even better classification performances, with significant reduction in the number of features that need to be computed.

     

Approximate parameter inference in systems biology using gradient matching: a comparative evaluation

Background

A challenging problem in current systems biology is that of parameter inference in biological pathways expressed as coupled ordinary differential equations (ODEs). Conventional methods that repeatedly numerically solve the ODEs have large associated computational costs. Aimed at reducing this cost, new concepts using gradient matching have been proposed, which bypass the need for numerical integration. This paper presents a recently established adaptive gradient matching approach, using Gaussian processes (GPs), combined with a parallel tempering scheme, and conducts a comparative evaluation with current state-of-the-art methods used for parameter inference in ODEs. Among these contemporary methods is a technique based on reproducing kernel Hilbert spaces (RKHS). This has previously shown promising results for parameter estimation, but under lax experimental settings. We look at a range of scenarios to test the robustness of this method. We also change the approach of inferring the penalty parameter from AIC to cross validation to improve the stability of the method.

Methods

Methodology for the recently proposed adaptive gradient matching method using GPs, upon which we build our new method, is provided. Details of a competing method using RKHS are also described here.

Results

We conduct a comparative analysis for the methods described in this paper, using two benchmark ODE systems. The analyses are repeated under different experimental settings, to observe the sensitivity of the techniques.

Conclusions

Our study reveals that for known noise variance, our proposed method based on GPs and parallel tempering achieves overall the best performance. When the noise variance is unknown, the RKHS method proves to be more robust.

     

A prospective observational cohort study in primary care practices to identify factors associated with treatment failure in <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> skin and soft tissue infections

Background

The incidence of outpatient visits for skin and soft tissue infections (SSTIs) has substantially increased over the last decade. The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has made the management of S. aureus SSTIs complex and challenging. The objective of this study was to identify risk factors contributing to treatment failures associated with community-associated S. aureus skin and soft tissue infections SSTIs.

Methods

This was a prospective, observational study among 14 primary care clinics within the South Texas Ambulatory Research Network. The primary outcome was treatment failure within 90 days of the initial visit. Univariate associations between the explanatory variables and treatment failure were examined. A generalized linear mixed-effect model was developed to identify independent risk factors associated with treatment failure.

Results

Overall, 21% (22/106) patients with S. aureus SSTIs experienced treatment failure. The occurrence of treatment failure was similar among patients with methicillin-resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19 vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with S. aureus SSTIs was a duration of infection of ≥7 days prior to initial visit [aOR, 6.02 (95% CI 1.74–19.61)] and a lesion diameter size ≥5 cm [5.25 (1.58–17.20)].

Conclusions

Predictors for treatment failure included a duration of infection for ≥7 days prior to the initial visit and a wound diameter of ≥5 cm. A heightened awareness of these risk factors could help direct targeted interventions in high-risk populations.

     

Trends in paediatric and adult bloodstream infections at a Ghanaian referral hospital: a retrospective study

Background

Bloodstream infections (BSI) are life-threatening emergencies. Identification of the common pathogens and their susceptibility patterns is necessary for timely empirical intervention.

Methods

We conducted a 4-year retrospective analysis of blood cultures from all patients excluding neonates at the Korle-Bu Teaching hospital, Ghana, from January 2010 through December 2013. Laboratory report data were used to determine BSI, blood culture contamination, pathogen profile, and antimicrobial resistance patterns.

Results

Overall, 3633 (23.16 %) out of 15,683 blood cultures were positive for various organisms. Pathogen-positive cultures accounted for 1451 (9.3 %, 95 % CI 8.5–9.8 %). Infants recorded the highest true blood culture positivity (20.9 %, n = 226/1083), followed by the elderly (13.3 %, n = 80/601), children (8.9 %, n = 708/8000) and adults (7.2 %, n = 437/6000) (p = 0.001 for Marascuilo’s post hoc). Overall occurrence of BSI declined with increasing age-group (p = 0.001) but the type of isolates did not vary with age except for Citrobacter, Escherichia coli, Klebsiella, Salmonella, and Enterococcus species. Gram negative bacteria predominated in our study (59.8 %, n = 867/1451), but the commonest bacterial isolate was Staphylococcus aureus (21.9 %, n = 318/1451)—and this trend run through the various age-groups. From 2010 to 2013, we observed a significant trend of yearly increase in the frequency of BSI caused by cephalosporin-resistant enterobacteria (Chi square for trend, p = 0.001). Meropenem maintained high susceptibility among all Gram-negative organisms ranging from 96 to 100 %. Among Staphylococcus aureus, susceptibility to cloxacillin was 76.6 %.

Conclusion

Our study shows a significantly high blood culture positivity in infants as compared to children, adults and the elderly. There was a preponderance of S. aureus and Gram-negative bacteria across all age-groups. Meropenem was the most active antibiotic for Gram-negative bacteria. Cloxacillin remains a very useful anti-staphylococcal agent.

     

Smear positive pulmonary tuberculosis and associated factors among homeless individuals in Dessie and Debre Birhan towns,Northeast Ethiopia

Background

Tuberculosis (TB) remains one of the globe’s deadliest communicable diseases. The homeless individuals are at high risk to acquire TB and multi-drug resistant TB (MDR-TB), because of their poor living conditions and risky behaviors. Tuberculosis and MDR-TB in the homeless individuals can pose a risk to entire communities. However, the magnitude of the problem is not known in Ethiopia. Therefore, the aim of this study was to determine the prevalence and associated factors of smear positive pulmonary TB (PTB) and MDR-TB among homeless individuals in Dessie and Debre Birhan towns, Northeast Ethiopia.

Methods

A community based cross-sectional study design was conducted from September 2014 to June 2015. Using an active screening with cough of ≥2 weeks, 351 TB suspects homeless individuals were participated in this study. Data were collected by using pre-tested and structured questionnaire. Spot-morning-spot sputum sample was collected and examined for acid-fast bacilli (AFB) using fluorescence microscopy by Auramine O staining technique. All AFB positive sputum was further analyzed by GeneXpert for detection of Mycobacterium tuberculosis complex and rifampicin resistant gene. Univariate and multivariate logistic regressions were applied to identify factors associated with smear positive PTB and P value <0.05 was considered as statistically significant.

Results

The prevalence of smear positive PTB was 2.6 % (95 % CI 1.3–5) among TB suspect homeless individuals. Extrapolation of this study finding implies that there were 505 smear positive PTB per 100,000 homeless individuals. All smear positive PTB sputum specimens were further analyzed by GeneXpert assay, the assay confirmed that all were positive for MTBC but none were resistant to RIF or MDR. Smoking cigarette regularly for greater than 5 years (AOR 10.1, 95 % CI 1.1, 97.7), body mass index lower than 18.5 (AOR 6.9, 95 % CI 1.12, 41.1) and HIV infection (AOR 6.8, 95 % CI 1.1, 40.1) were significantly associated with smear positive PTB.

Conclusion

The prevalence of smear positive PTB among TB suspect homeless individuals was 2.6 %. Among smear positive PTB, prevalence of HIV co-infection was very high 5 (55.5 %). Smoking cigarette regularly for greater than 5 years, BMI lower than 18.5 and HIV infection were factors associated with smear positive PTB. Special emphasis is needed for homeless individuals to exert intensive effort to identify undetected TB cases to limit the circulation of the disease into the community.