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Importance: Broad range assay for accurate and sensitive diagnostics., Competing Interests: The authors declare no conflict of interest.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is estimated to affect 0.4%-2.5% of the global population. Most cases are unexplained; however, some patients describe an antecedent viral infection or response to antiviral medications. We report here a multicenter study for the presence of viral nucleic acid in blood, feces, and saliva of patients with ME/CFS using polymerase chain reaction and high-throughput sequencing. We found no consistent group-specific differences other than a lower prevalence of anelloviruses in cases compared to healthy controls. Our findings suggest that future investigations into viral infections in ME/CFS should focus on adaptive immune responses rather than surveillance for viral gene products., (© 2023 Wiley Periodicals LLC.)

In this issue of Neuron, Watakabe et al. 1 utilize serial two-photon tomography to reveal that the intra- and inter-regional prefrontal cortex projections in the marmoset brain terminate with two characteristic patterns, columnar and diffused, both of which display a topographically organized gradient., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Access of sensory information to consciousness has been linked to the ignition of content-specific representations in association cortices. How does ignition interact with intrinsic cortical state fluctuations to give rise to conscious perception? We addressed this question in the prefrontal cortex (PFC) by combining multi-electrode recordings with a binocular rivalry (BR) paradigm inducing spontaneously driven changes in the content of consciousness, inferred from the reflexive optokinetic nystagmus (OKN) pattern. We find that fluctuations between low-frequency (LF, 1-9 Hz) and beta (∼20-40 Hz) local field potentials (LFPs) reflect competition between spontaneous updates and stability of conscious contents, respectively. Both LF and beta events were locally modulated. The phase of the former locked differentially to the competing populations just before a spontaneous transition while the latter synchronized the neuronal ensemble coding the consciously perceived content. These results suggest that prefrontal state fluctuations gate conscious perception by mediating internal states that facilitate perceptual update and stability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Despite the considerable progress of in vivo neural recording techniques, inferring the biophysical mechanisms underlying large scale coordination of brain activity from neural data remains challenging. One obstacle is the difficulty to link high dimensional functional connectivity measures to mechanistic models of network activity. We address this issue by investigating spike-field coupling (SFC) measurements, which quantify the synchronization between, on the one hand, the action potentials produced by neurons, and on the other hand mesoscopic "field" signals, reflecting subthreshold activities at possibly multiple recording sites. As the number of recording sites gets large, the amount of pairwise SFC measurements becomes overwhelmingly challenging to interpret. We develop Generalized Phase Locking Analysis (GPLA) as an interpretable dimensionality reduction of this multivariate SFC. GPLA describes the dominant coupling between field activity and neural ensembles across space and frequencies. We show that GPLA features are biophysically interpretable when used in conjunction with appropriate network models, such that we can identify the influence of underlying circuit properties on these features. We demonstrate the statistical benefits and interpretability of this approach in various computational models and Utah array recordings. The results suggest that GPLA, used jointly with biophysical modeling, can help uncover the contribution of recurrent microcircuits to the spatio-temporal dynamics observed in multi-channel experimental recordings., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Safavi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Aim: Herpes simplex CNS infection is a rare but important cause of neurological disability. Long term outcomes after HSV CNS infection in Australia have not yet been fully described. We sought to provide a comprehensive review of HSV CNS infection in children using a retrospective 13-year evaluation of statewide laboratory and clinical records and a parent survey conducted at least one year after the initial infection., Methods: All positive PCR HSV 1 and 2 results from cerebrospinal fluid (CSF) or brain tissue were obtained from Queensland pathology providers for children aged 0-16 years between 1 January 2005 and 31 December 2017. Clinical data were obtained from patient records and longer-term outcomes via parent survey at least 1 year after initial infection., Results: Forty-three children were identified over the 13-year period, 17 (39.5%) neonates and 26 (60.4%) non-neonates. The annual incidence for HSV CNS infection in Queensland children aged ≤16 years was 0.3/100 000 (95% confidence intervals (CIs): 0.2-0.4) with neonates at highest risk (incidence 2.5/100 000 live births, 95% CI: 1.5-3.9). HSV 1 was the predominant serotype in both neonates and non-neonates (9/17, 52.9% neonates and 19/26, 73.1% non-neonates). Seven (16.3%) children died, five (5/17, 29.4% neonates), directly attributable to HSV CNS infection (all neonates). Twenty-five (58.1%) had neurological morbidity at discharge (9/17 neonates (52.9%) vs. 16/26 (61.5%) non-neonates) and 20/27 (74.1%) reported long-term neurological morbidity at follow-up (5/9 neonates (55.6%) vs. 15/18 non-neonates (83.3%)). Seven children (two neonates and four non-neonates) with long-term neurological sequelae had no neurological morbidity identified at discharge., Conclusion: Significant long-term neurologic sequelae were seen in children with HSV CNS infection even in children with no neurological disability identified at discharge from hospital. Careful neurodevelopmental follow-up of all children is recommended., (© 2022 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Children's vision screening children commonly uses optotype-based visual acuity or instrument-based methods measuring amblyogenic risk factors (ARFs)., Objective: To compare the performance of the Spot Vision Screener (SVS) (PediaVision, Welch Allyn, NY) and a nurse-administered visual acuity screen (NVAS) in identifying ARFs and decreased visual acuity., Methods: A prospective, cross-sectional population-based study of preschool children in South-East Queensland, Australia. Eligible participants had both forms of screening by trained community nurses. All children with an abnormal result by either method as well as a cohort of randomly selected children who passed both assessments were assessed at a tertiary paediatric ophthalmology clinic., Results: Over a 10 month period, 2237 children (mean age; 64.4 ± 4.0 months) were screened from 38 schools. 6.4% of children failed SVS and 8.3% failed NVAS (with 3.8% overlap, failing both). The positive predictive value (PPV) in identifying either ARFs and/or reduced VA for the SVS and NVAS was 70.4% (95% Confidence Interval (CI): 61.6%-78.2%) and 60.5% (95% CI: 52.6%-67.9%) respectively. Highest PPV to detect either ARFs and/or reduced VA was achieved by a 'hybrid' method by combining failed NVAS and failed SVS: 91.0% (95% CI: 82.4 to 96.3) but this would risk children with sight impairment being missed in the community., Conclusion: To our knowledge, this is the first population-based study providing detailed comparative measures of diagnostic accuracy for NVAS and SVS in preschool children. One in ten preschool children failed one or both screens. A number of children who required ophthalmic intervention were missed if only one screening method was utilized.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) accounts for a high proportion of paediatric outpatient visits in Australia. Shared care by general practitioners (GPs) would deliver more timely care, closer to home, however GPs indicated the need for interprofessional training support. This study describes the use of Project ECHO ® , a guided practice model, to support GPs with ADHD management, by connecting them virtually with an interprofessional team of paediatric specialists using a structured methodology., Methods: A retrospective pre/post-knowledge and self-efficacy survey across twenty-seven aspects of ADHD management was administered, using a seven-point Likert scale., Results: Significant improvement (p < 0.001) in provider self-efficacy was demonstrated across all tested domains., Discussion: Use of the ECHO model™ by an interprofessional team of paediatric specialists achieved an increase in GP knowledge and self-efficacy in the local management of children and young people with complex healthcare needs. Learnings indicate viability to expand the application of the ECHO model™ to address fragmentation for other priority populations across the Australian healthcare and human service sector landscape., Conclusion: Use of the ECHO model™ to support and train GPs was successful. Integration of care was achieved through strengthened partnerships between content and context experts, and the ECHO model™'s case-based learning methodology., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

A major debate about the neural correlates of conscious perception concerns its cortical organization, namely, whether it includes the prefrontal cortex (PFC), which mediates executive functions, or it is constrained within posterior cortices. It has been suggested that PFC activity during paradigms investigating conscious perception is conflated with post-perceptual processes associated with reporting the contents of consciousness or feedforward signals originating from exogenous stimulus manipulations and relayed via posterior cortical areas. We addressed this debate by simultaneously probing neuronal populations in the rhesus macaque (Macaca mulatta) PFC during a no-report paradigm, capable of instigating internally generated transitions in conscious perception, without changes in visual stimulation. We find that feature-selective prefrontal neurons are modulated concomitantly with subjective perception and perceptual suppression of their preferred stimulus during both externally induced and internally generated changes in conscious perception. Importantly, this enables reliable single-trial, population decoding of conscious contents. Control experiments confirm significant decoding of stimulus contents, even when oculomotor responses, used for inferring perception, are suppressed. These findings suggest that internally generated changes in the contents of conscious visual perception are reliably reflected within the activity of prefrontal populations in the absence of volitional reports or changes in sensory input., (© 2022. The Author(s).)

The lateral dimension of an alluvial river - floodplains - provides a plethora of goods and services for human needs. Also, it supports the richest and diverse riverine ecosystems on Earth. But over-utilization of floodplain resources had impacted functions of river system adversely. So, the present study attempts to formulate a hydro-bio-geomorphological framework to assess the lateral dimension of a river system for sustainable management of river-floodplains and termed as river space in this paper. The study illustrates river space at seven hydro-meteorological sites situated on the main stem of the Ganga river in the ~750 km stretch that lies between Haridwar and Prayagraj cities. For hydrological aspect, the flood frequency analysis is used to identify flood inundation widths for floods of different return periods with the help of the rating curve and derived cross-section from satellite imagery. Bio-geomorphological aspects are taken into consideration for corroborating the hydrologically assessed river widths (lateral dimension). The present study suggests that the minimum river space should be equal to the lateral width corresponding to the 1-year return period flood. In the present hydro-meteorological sites in the middle Ganga plains, it ranges from 2 to 21 km. Overall, the present study gives an insight of a simple and logical approach that could be beneficial for the biomic restoration of rivers and their floodplains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Assay sensitivity can be a limiting factor in the use of PCR as a tool for the detection of tick-borne pathogens in blood. We evaluated the performance of Tick-borne disease Capture Sequencing Assay (TBDCapSeq), a capture sequencing assay targeting tick-borne agents, to test 158 whole blood specimens obtained from the Lyme Disease Biobank. These included samples from 98 individuals with signs and symptoms of acute Lyme disease, 25 healthy individuals residing in Lyme disease endemic areas, and 35 samples collected from patients admitted to the Massachusetts General Hospital or referred to the infectious disease clinic. Compared to PCR, TBDCapSeq had better sensitivity and could identify infections with a wider range of tick-borne agents. TBDCapSeq identified a higher rate of samples positive for Borrelia burgdorferi (8 vs. 1 by PCR) and Babesia microti (26 vs. 15 by PCR). TBDCapSeq also identified previously unknown infections with Borrelia miyamotoi , Ehrlichia , and Rickettsia species. Overall, TBDCapSeq identified a pathogen in 43 samples vs. 23 using PCR, with four co-infections detected versus zero by PCR. We conclude that capture sequencing enables superior detection of tick-borne agents relative to PCR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sanchez-Vicente, Jain, Tagliafierro, Gokden, Kapoor, Guo, Horn, Lipkin and Tokarz.)

Background and Objectives: Infants hospitalized with bronchiolitis are commenced on nasogastric feeding to maintain hydration. Feeding strategies vary according to physician or institution preference. The current study hypothesized that continuous nasogastric feeding would prolong length of stay (LOS) when compared to bolus feeding., Methods: A randomized, parallel-group, superiority clinical trial was performed within an Australian children's hospital throughout 2 bronchiolitis seasons from May 2018 to October 2019. Infants <12 months hospitalized with bronchiolitis and requiring supplemental nasogastric feeding were randomly assigned to continuous or bolus nasogastric regimens. LOS was the primary outcome. Secondary outcome measures included pulmonary aspirations and admissions to intensive care., Results: The intention-to-treat analysis included 189 patients: 98 in the bolus nasogastric feeding group and 91 in the continuous group. There was no significant difference in LOS (median LOS of the bolus group was 54.25 hours [interquartile range 40.25-82] and 56 hours [interquartile range 38-78.75] in the continuous group). A higher proportion of admissions to intensive care was detected in the continuous group (28.57% [26 of 91] of the continuous group vs 11.22% [11 of 98] of the bolus group [P value 0.004]). There were no clinically significant pulmonary aspirations or statistically significant differences in vital signs between the groups within 6 hours of feed initiation., Conclusions: No significant difference in LOS was found between bolus and continuous nasogastric feeding strategies for infants hospitalized with bronchiolitis. The continuous feeding group had a higher proportion of intensive care admissions, and there were no aspiration events., Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Obstetricians and gynaecologists (O&Gs) are at a risk of work-related musculoskeletal injuries (WRMI) on a daily basis., Aims: To describe the prevalence of WRMI among O&Gs in Australia and New Zealand, explore risk factors for such injuries, and evaluate their impact., Methods: An online survey of Fellows of Royal Australian and New Zealand College of Obstetricians and Gynaecologists was conducted in July 2016. It comprised questions on personal attributes, type of work, site and cause of WRMI, if any and treatment required., Results: We received responses from 765 O&Gs giving a response rate of 38.3% (765/1997). Four hundred and ten specialists (53.6%) reported suffering a WRMI at some point, including 252 (32.9%) who reported multiple injuries. In multivariable analysis, females had increased risk of WRMI (odds ratio (OR): 2.12; 95% CI: 1.54-2.91) and among generalists and subspecialists, gynaecological oncologists had highest risk for WRMI (OR: 3.13; 95% CI: 1.21-8.14). Commonest sites of injury were back (218/633, 34.4%) and shoulder (131/633, 20.7%). Laparoscopic surgery (117/633, 18.5%) was the commonest cause of injury. Treatment was required for 88.6% of injuries (561/633) including 8.4% (53/633) of cases which required surgery. Ongoing symptoms post-injury were reported for 52.1% of injuries (330/633) and in 25.8% (163/633) of instances the practitioner needed to modify their scope of work., Conclusion: This survey among a large cohort of O&Gs shows a high prevalence of WRMI with a profound negative impact on the practitioner and profession. There is a pressing need to advocate for improved ergonomics in their workplaces., (© 2021 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Inadequate sensitivity has been the primary limitation for implementing high-throughput sequencing for studies of tick-borne agents. Here we describe the development of TBDCapSeq, a sequencing assay that uses hybridization capture probes that cover the complete genomes of the eleven most common tick-borne agents found in the United States. The probes are used for solution-based capture and enrichment of pathogen nucleic acid followed by high-throughput sequencing. We evaluated the performance of TBDCapSeq to surveil samples that included human whole blood, mouse tissues, and field-collected ticks. For Borrelia burgdorferi and Babesia microti, the sensitivity of TBDCapSeq was comparable and occasionally exceeded the performance of agent-specific quantitative PCR and resulted in 25 to > 10,000-fold increase in pathogen reads when compared to standard unbiased sequencing. TBDCapSeq also enabled genome analyses directly within vertebrate and tick hosts. The implementation of TBDCapSeq could have major impact in studies of tick-borne pathogens by improving detection and facilitating genomic research that was previously unachievable with standard sequencing approaches.

Background: National neonatal surveillance for herpes simplex virus (HSV) disease suggests that the incidence of HSV disease may be higher in Queensland (QLD) than in other Australian States. We sought to investigate the incidence via a retrospective 13-year evaluation of statewide laboratory data, autopsy data and linked clinical records of infants with laboratory confirmed infection., Methods: All positive polymerase chain reaction HSV 1 and 2 results were obtained for infants 0-3 months of age from January 1, 2005 to December 31, 2017. Clinical data were obtained from patient records and parent questionnaires were used to evaluate long-term sequelae., Results: One hundred seventy-two infants with HSV positive polymerase chain reaction results: 121 (70.3%) with HSV 1. Of 104 (60.5%) infants with signs of HSV disease, 76 (73.1%) were neonates (≤28 days of age) [incidence 9.6 (95% confidence interval, 7.0-11.5) per 100,000 live births] and 28 (26.9%) were young infants (29-90 days of age) [3.6 (95% confidence interval, 2.4-5.4) per 100,000 live births]. The annual incidence of neonatal HSV disease increased significantly in Queensland over the study period (P < 0.01). Of the 76 neonates with HSV disease, 58 (76.3%) presented with the skin, eye, mouth (SEM) disease, 17 (22.4%) with HSV encephalitis and 11 (14.5%) had disseminated disease. Young infants presented with HSV skin, eye, mouth disease (21, 75.0%) or HSV encephalitis (6, 21.4%). Death occurred in 12/104 (11.5%) infants (all neonates) with 10 attributable to HSV disease., Conclusion: The incidence of neonatal HSV disease in QLD is almost 3 times the national reported incidence. Further research is being undertaken to explore reasons for this change and implications for practice., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Bronchiolitis is the most common reason for hospital admission in infants, with one third requiring oxygen therapy due to hypoxemia. It is unknown what proportion of hypoxemic infants with bronchiolitis can be managed with nasal high-flow in room air and their resulting outcomes. Objectives and Settings: To assess the effect of nasal high-flow in room air in a subgroup of infants with bronchiolitis allocated to high-flow therapy in a recent multicenter randomized controlled trial. Patients and Interventions: Infants allocated to the high-flow arm of the trial were initially treated with room air high-flow if saturations were ≥85%. Subsequently, if oxygen saturations did not increase to ≥92%, oxygen was added and FiO 2 was titrated to increase the oxygen saturations. In this planned sub-study, infants treated during their entire hospital stay with high-flow room air only were compared to infants receiving either standard-oxygen or high-flow with oxygen. Baseline characteristics, hospital length of stay and length of oxygen therapy were compared. Findings: In the per protocol analysis 64 (10%) of 630 infants commenced on high-flow room air remained in room air only during the entire stay in hospital. These infants on high-flow room air were on average older and presented with moderate hypoxemia at presentation to hospital. Their length of respiratory support and length of stay was also significantly shorter. No pre-enrolment factors could be identified in a multivariable analysis. Conclusions: In a small sub-group of hypoxemic infants with bronchiolitis hypoxemia can be reversed with the application of high-flow in room air only. Trial registration: ACTRN12615001305516., (Copyright © 2019 Franklin, Babl, Gibbons, Pham, Hasan, Schlapbach, Oakley, Craig, Furyk, Neutze, Moloney, Gavranich, Shirkhedkar, Kapoor, Grew, Fraser, Dalziel, Schibler and PARIS and PREDICT.)

Background: Conventionally used soybean oil-based lipid emulsion (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols that may contribute to adverse effects in preterm infants. The newer lipid emulsions (LE) from different lipid sources are currently available for use in preterm infants., Objectives: To compare the safety and efficacy of all LE for parenteral nutrition (PN) in preterm infants (less than 37 weeks' gestation) including preterm infants with surgical conditions or parenteral nutrition-associated liver disease (PNALD)/cholestasis using direct comparisons and pair-wise meta-analyses., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 July 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and WHO's Trials Registry and Platform), and reference lists of retrieved articles., Selection Criteria: Randomised or quasi-randomised controlled studies in preterm infants with or without surgical conditions or PNALD within the first six months of life., Data Collection and Analysis: Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting statistical significance of results., Main Results: We included 29 studies (n = 2037) in this review. LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil-LE (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soybean oil-LE (MFS-LE) and olive-fish-soybean oil-LE (OFS-LE); 2. conventional S-LE; 3. alternative-LE (e.g. MCT-soybean oil-LE (MS-LE), olive-soybean oil-LE and borage oil-based LE).We considered the following broad comparisons: fish oil LE versus non-fish oil LE; fish oil LE versus another fish oil LE; alternative-LE versus S-LE; alternative-LE versus another alternative-LE in preterm infants less than 37 weeks' gestation, preterm infants with surgical conditions and preterm infants with PNALD/cholestasis. Separate subgroup comparisons of each LE preparation were included within these broader groups.Most studies in preterm infants used PN for mean duration of four weeks or less and for longer duration in infants with cholestasis or surgical conditions.We defined the primary outcome of PNALD/cholestasis as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. There was heterogeneity in definitions used by the included studies with Cbil cut-offs ranging from 17.1 μmol/L (1 mg/dL) up to 50 μmol/L (about 3 mg/dL).In preterm infants, meta-analysis found no evidence of a difference in the incidence of PNALD/cholestasis (Cbil cut-off: 2 mg/dl) between fish oil-LEs and all non-fish oil LEs (typical risk ratio (RR) 0.61, 95% confidence interval (CI) 0.24 to 1.56; typical risk difference (RD) -0.03, 95% CI -0.08 to 0.02; 4 studies; n = 328; low-quality evidence).We also considered an outcome allowing for any definition of PNALD (different Cbil cutoffs). In the meta-analysis for PNALD/cholestasis, using any definition and restricted to low or unclear risk of bias studies, there was no evidence of a difference between fish oil LE and all non-fish oil LE for incidence of cholestasis (typical RR 0.80, 95% CI 0.53 to 1.21; typical RD -0.02, 95% CI -0.05 to 0.02; 10 studies; n = 1024; low-quality evidence). There was no evidence of difference in subgroup meta-analyses of individual LE types in any comparison.In preterm infants with surgical conditions or cholestasis, there was only one small study each reporting no evidence of a difference in incidence or resolution of cholestasis respectively with use of a pure F-LE versus S-LE (using a Cbil cut-off of 2 mg/dL).In preterm infants with PNALD/cholestasis (using any definition), the meta-analysis showed significantly less cholestasis with the use of fish oil-LE compared to S-LE (typical RR 0.54, 95% CI 0.32 to 0.91; typical RD -0.39, 95% CI -0.65 to -0.12; number needed to treat for an additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). However, this outcome had a very low number of participants from two small studies with methodological differences, one of which was terminated early, increasing the uncertainty about effect estimates.There were no differences between LE types in pair-wise meta-analyses for growth in preterm infants. There was paucity of studies in preterm infants with surgical conditions or cholestasis to perform meta-analyses for growth and most other outcomes.In the secondary outcomes for preterm infants, there was no difference between fish-oil LE and non-fish oil LE in meta-analysis for severe retinopathy of prematurity (ROP) (stage 3 or greater, or requiring surgery: typical RR 0.80, 95% CI 0.55 to 1.16; typical RD -0.03, 95% CI -0.07 to 0.02; 7 studies; n = 731; very low-quality evidence). There were no differences in the LE types in pair-wise meta-analyses for death, bronchopulmonary dysplasia (BPD), ventilation duration, patent ductus arteriosus, sepsis, necrotising enterocolitis, intraventricular haemorrhage, periventricular leukomalacia, jaundice, hyperglycaemia, hypertriglyceridaemia, intrahepatocellular lipid content and conjugated bilirubin levels in any comparison.In surgical infants, one study (n = 19) reported no differences in death, sepsis rates, Cbil and neurodevelopmental outcomes with pure F-LE versus S-LE.In infants with cholestasis, there were no evidence of differences in death or sepsis in meta-analyses between fish oil-LE and S-LE; (2 studies; n = 40; very low-quality evidence)., Authors' Conclusions: In the current review, we did not find any particular LE with or without fish oil to be better than another LE in preterm infants for prevention of PNALD/cholestasis, growth, mortality, ROP, BPD and other neonatal outcomes.In preterm infants with surgical conditions or cholestasis, there is currently insufficient evidence from randomised studies to determine with any certainty if fish oil LEs offer advantage in prevention or resolution of cholestasis or in any other clinical outcome.Further research, with larger well-designed trials, is warranted to evaluate the ideal composition of LE in preterm infants and the role of fish oil-containing and other LEs in the prevention and resolution of PNALD, ROP and other clinical outcomes.

Background: Lipid emulsions (LE) form a vital component of infant nutrition for critically ill, late preterm or term infants, particularly for those with gastrointestinal failure. Conventionally used soybean oil-based LE (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols, which may contribute to adverse effects including parenteral nutrition-associated liver disease (PNALD)., Objectives: To compare the safety and efficacy of all LE for parenteral nutrition (PN) in term and late preterm infants (between 34 weeks' gestation and 36 weeks' and six days' gestation) with or without surgical conditions or PNALD within first six months of life, using all possible direct comparisons., Search Methods: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 June 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and the WHO's Trials Registry), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised or quasi-randomised controlled studies in term and late preterm infants, with or without surgical conditions or PNALD., Data Collection and Analysis: Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting the conventional statistical significance of results., Main Results: The review included nine randomised studies (n = 273). LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soy oil-LE (MFS-LE) and olive-fish-soy-LE (OFS-LE)); 2. conventional pure S-LE; 3. alternative-LE (e.g. MCT-soy-LE (MS-LE), olive-soy-LE (OS-LE) and borage oil-based LE).We considered four broad comparisons: 1. all fish oil LE versus non-fish oil LE (6 studies; n = 182); 2. fish oil LE versus another fish oil LE (0 studies); 3. alternative-LE versus S-LE (3 studies; n = 91); 4. alternative-LE versus another alternative-LE (0 studies) in term and late preterm infants (0 studies), term and late preterm infants with surgical conditions (7 studies; n = 233) and term and late preterm infants with PNALD/cholestasis (2 studies; n = 40).PNALD/cholestasis was defined as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. We put no restriction on timing of PNALD detection. There was heterogeneity in definitions and time points for detecting PNALD in the included studies.We found one study each in surgical infants and in infants with cholestasis, showing no evidence of difference in incidence or resolution of PNALD/cholestasis (Cbil cut-off: 2 mg/dL) with use of fish oil-containing LE compared to S-LE.We considered an outcome allowing for any definition of PNALD (different Cbil cut-off levels). In infants with surgical conditions and no pre-existing PNALD, meta-analysis showed no difference in the incidence of PNALD/cholestasis (any definition) with use of fish oil-containing LE compared to S-LE (typical risk ratio (RR) 1.20, 95% confidence interval (CI) 0.38 to 3.76; typical risk difference (RD) 0.03, 95% CI -0.14 to 0.20; 2 studies; n = 68; low-quality evidence). In infants with PNALD/cholestasis (any definition), use of fish oil-LEs was associated with significantly less cholestasis compared to the S-LE group (typical risk ratio (RR) 0.54, 95% confidence interval (CI) 0.32 to 0.91; typical risk difference (RD) -0.39, 95% CI -0.65 to -0.12; number needed to treat for additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). This outcome had very low number of participants from two small studies with differences in study methodology and early termination in one study, which increased uncertainty about the effect estimates.One study in infants with cholestasis reported significantly better weight gain with a pure fish oil LE compared to a 10% S-LE (45 g/week, 95% CI 15.0 to 75.0; n = 16; very low-quality evidence). There were no significant differences in growth parameters in studies with surgical populations.For the secondary outcomes, in infants with cholestasis, one study (n = 24) reported significantly lower conjugated bilirubin levels but higher gamma glutamyl transferase levels with MOFS-LE (SMOFlipid) versus S-LE (Intralipid) and another study (n = 16), which was terminated early, reported significantly higher rates of rise in alanine aminotransferase (ALT) and conjugated bilirubin levels in the S-LE group compared to pure F-LE (Omegaven).In surgical infants, two studies each reported on hypertriglyceridaemia and Cbil levels with one study in each outcome showing significant benefit with use of a F-LE and the other study showing no difference between the groups. Meta-analysis was not performed for either of these outcomes as there were only two studies showing conflicting results with high heterogeneity between the studies.There was no evidence of differences in death, sepsis, alkaline phosphatase and ALT levels in infants with surgical conditions or cholestasis (very low-quality evidence).One study reported neurodevelopmental outcomes at six and 24 months in infants with surgical conditions (n = 11) with no evidence of difference with use of pure F-LE versus S-LE. Another study in infants with cholestasis (n = 16) reported no difference in head growth velocity between pure F-LE versus S-LE.GRADE quality of evidence ranged from low to very low as the included studies were small single-centre studies. Three of the six studies that contributed data to the review were terminated early for various reasons., Authors' Conclusions: Based on the current review, there is insufficient data from randomised studies to determine with any certainty, the potential benefit of any LE including fish oil-containing LEs over another LE, for prevention or resolution of PNALD/cholestasis or any other outcomes in term and late preterm infants with underlying surgical conditions or cholestasis. There were no studies in infants without surgical conditions or cholestasis.Further research is required to establish role of fish oil or lipids from other sources in LEs to improve PNALD/cholestasis, and other clinical outcomes in parenterally fed term and late preterm infants.

Bats are implicated as natural reservoirs for a wide range of zoonotic viruses including SARS and MERS coronaviruses, Ebola, Marburg, Nipah, Hendra, Rabies and other lyssaviruses. Accordingly, many One Health surveillance and viral discovery programs have focused on bats. In this report we present viral metagenomic data from bats collected in the Kingdom of Saudi Arabia [KSA]. Unbiased high throughput sequencing of fecal samples from 72 bat individuals comprising four species; lesser mouse-tailed bat (Rhinopoma hardwickii), Egyptian tomb bat (Taphozous perforatus), straw-colored fruit bat (Eidolon helvum), and Egyptian fruit bat (Rousettus aegyptiacus) revealed molecular evidence of a diverse set of viral families: Picornaviridae (hepatovirus, teschovirus, parechovirus), Reoviridae (rotavirus), Polyomaviridae (polyomavirus), Papillomaviridae (papillomavirus), Astroviridae (astrovirus), Caliciviridae (sapovirus), Coronaviridae (coronavirus), Adenoviridae (adenovirus), Paramyxoviridae (paramyxovirus), and unassigned mononegavirales (chuvirus). Additionally, we discovered a bastro-like virus (Middle East Hepe-Astrovirus), with a genomic organization similar to Hepeviridae. However, since it shared homology with Hepeviridae and Astroviridae at ORF1 and in ORF2, respectively, the newly discovered Hepe-Astrovirus may represent a phylogenetic bridge between Hepeviridae and Astroviridae., Competing Interests: The authors have declared that no competing interests exist.

The role of lateral prefrontal cortex (LPFC) in mediating conscious perception has been recently questioned due to potential confounds resulting from the parallel operation of task related processes. We have previously demonstrated encoding of contents of visual consciousness in LPFC neurons during a no-report task involving perceptual suppression. Here, we report a separate LPFC population that exhibits task-phase related activity during the same task. The activity profile of these neurons could be captured as canonical response patterns (CRPs), with their peak amplitudes sequentially distributed across different task phases. Perceptually suppressed visual input had a negligible impact on sequential firing and functional connectivity structure. Importantly, task-phase related neurons were functionally segregated from the neuronal population, which encoded conscious perception. These results suggest that neurons exhibiting task-phase related activity operate in the LPFC concurrently with, but segregated from neurons representing conscious content during a no-report task involving perceptual suppression., Competing Interests: The authors declare no competing interests.

Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes., Competing Interests: The authors declare no conflict of interest., (Copyright © 2018 the Author(s). Published by PNAS.)

Introduction: Sacrospinous hysteropexy is a uterine-preserving procedure for treatment of apical prolapse. We present a literature review evaluating the sacrospinous hysteropexy procedure and its current place in the surgical management of pelvic organ prolapse. Additionally, to assess the efficacy of the procedure, we performed a meta-analysis of studies comparing sacrospinous hysteropexy to vaginal hysterectomy and repair in terms of anatomical outcomes, complications, and repeat surgery., Methods: Major literature databases including MEDLINE (1946 to 2 April 2016), Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), and Embase (1947 to 2 April 2016) were searched for relevant studies. We used Cochrane Collaboration's Review Manager software to perform meta-analysis of randomized controlled studies and observational studies., Results: Vaginal sacrospinous hysteropexy was first performed in 1989 and is similar in technique to sacrospinous colpopexy. Two randomized controlled trials and four cohort studies (n = 651) were included in the meta-analysis. Apical failure rates after sacrospinous hysteropexy versus vaginal hysterectomy were not significantly different, although the trend favored vaginal hysterectomy [odds ratio (OR) 2.08; 95% confidence interval (CI) 0.76-5.68]. Rates of repeat surgery for prolapse were not significantly different between the two groups (OR 0.99; 95% CI 0.41-2.37). The most significant disadvantage of uterine-preservation prolapse surgery when compared with hysterectomy is the lack of prevention and diagnosis of uterine malignancy., Conclusion: Sacrospinous hysteropexy is a safe and effective procedure for pelvic organ prolapse and has comparable outcomes to vaginal hysterectomy with repair.

The Mapputta group comprises antigenically related viruses indigenous to Australia and Papua New Guinea that are included in the family Bunyaviridae but not currently assigned to a specific genus. We determined and analyzed the genome sequences of five Australian viruses isolated from mosquitoes collected during routine arbovirus surveillance in Western Australia (K10441, SW27571, K13190, and K42904) and New South Wales (12005). Based on matching sequences of all three genome segments to prototype MRM3630 of Trubanaman virus (TRUV), NB6057 of Gan Gan virus (GGV), and MK7532 of Maprik virus (MPKV), isolates K13190 and SW27571 were identified as TRUV, 12005 as GGV, and K42904 as a Mapputta group virus from Western Australia linking GGV and MPKV. The results confirmed serum neutralization data that had linked SW27571 to TRUV. The fifth virus, K10441 from Willare, was most closely related to Batai orthobunyavirus, presumably representing an Australian variant of the virus. Phylogenetic analysis also confirmed the close relationship of our TRUV and GGV isolates to two other recently described Australian viruses, Murrumbidgee virus and Salt Ash virus, respectively. Our findings indicate that TRUV has a wide circulation throughout the Australian continent, demonstrating for the first time its presence in Western Australia. Similarly, the presence of a virus related to GGV, which had been linked to human disease and previously known only from the Australian southeast, was demonstrated in Western Australia. Finally, a Batai virus isolate was identified in Western Australia. The expanding availability of genomic sequence for novel Australian bunyavirus variants supports the identification of suitably conserved or diverse primer-binding target regions to establish group-wide as well as virus-specific nucleic acid tests in support of specific diagnostic and surveillance efforts throughout Australasia., Competing Interests: The authors have declared that no competing interests exist.

Background: The pure soybean oil based lipid emulsions (S-LE) conventionally used for parenteral nutrition (PN) in preterm infants have high polyunsaturated fatty acid (PUFA) content. The newer lipid emulsions (LE) from alternative lipid sources with reduced PUFA content may improve clinical outcomes in preterm infants., Objectives: To determine the safety and efficacy of the newer alternative LE compared with the conventional S-LE for PN in preterm infants., Search Methods: We used the standard search strategy of the Cochrane Neonatal Review Group (CNRG) to search the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 7), MEDLINE (1946 to 31 July 2015), EMBASE (1947 to 31 July 2015), CINAHL (1982 to 31 July 2015), Web of Science (31 July 2015), conference proceedings, trial registries (clinicaltrials.gov, controlled-trials.com, WHO's ICTRP), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials., Selection Criteria: Randomised or quasi-randomised controlled trials in preterm infants (< 37 weeks), comparing newer alternative LE with S-LE., Data Collection and Analysis: Data collection and analysis conformed to the methods of the CNRG. We assessed the quality of evidence for important outcomes using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, in addition to reporting the conventional statistical significance of results., Main Results: Fifteen studies (N = 979 infants) are included in this review. Alternative LE including medium chain triglycerides/long chain triglycerides (MCT/LCT) LE (3 studies; n = 108), MCT-olive-fish-soy oil-LE (MOFS-LE; 7 studies; n = 469), MCT-fish-soy oil-LE (MFS-LE; 1 study; n = 60), olive-soy oil-LE (OS-LE; 7 studies; n = 406), and borage-soy oil-LE (BS-LE; 1 study; n = 34) were compared with S-LE. The different LE were also considered together to compare 'all fish oil containing-LE' versus S-LE (7 studies; n = 499) and 'all alternative LE' versus S-LE (15 studies; n = 979). Some studies had multiple intervention arms and were included in more than one comparison. No study compared pure fish oil-LE or structured-LE to S-LE.The GRADE quality of evidence (GRADE QoE) ranged from 'low' to 'very low.' Evidence came mostly from small single centre studies, many focusing on biochemical aspects as their primary outcomes, with optimal information size not achieved for the important clinical outcomes in any comparison.In the primary outcomes of the review there was a pooled effect towards decreased bronchopulmonary dysplasia (BPD) in OS-LE vs S-LE (4 studies, n = 261) not reaching statistical significance (typical risk ratio (RR) 0.69, 95% confidence interval (CI) 0.46 to 1.04, I² = 32%; typical risk difference (RD) -0.08, 95% CI -0.17 to 0.00, I² = 76%; GRADE QoE: 'very low'). No difference in BPD was observed in any other comparison. There were no statistically significant differences in the primary outcomes of death, growth rate (g/kg/day) or days to regain birth weight in any comparison.Retinopathy of prematurity (ROP) stage 1-2 was reported to be statistically significantly lower in one single centre study (n = 80) in the MOFS-LE group compared with the S-LE group (1/40 vs 12/40, respectively; RR 0.08, 95% CI 0.01 to 0.61; RD -0.27, 95% CI -0.43 to -0.12; number needed to benefit (NNTB) 4, 95% CI 2 to 8). However there were no statistically significant differences in the secondary outcome of ROP ≥ stage 3 in any of the individual studies or in any comparison (GRADE QoE: 'low' to 'very low'). No other study reported on ROP stages 1 and 2 separately.There were no statistically significant differences in the secondary outcomes of sepsis, PN associated liver disease (PNALD)/cholestasis, ventilation duration, necrotising enterocolitis (NEC) ≥ stage 2, jaundice requiring treatment, intraventricular haemorrhage grade III-IV, periventricular leukomalacia (PVL), patent ductus arteriosus (PDA), hypertriglyceridaemia, and hyperglycaemia in any comparison.No study reported on neurodevelopmental outcomes or essential fatty acid deficiency., Authors' Conclusions: All lipid emulsions in this review appeared to be safe and were well tolerated in preterm infants. Compared with the pure soy oil based LE, use of MOFS-LE was associated with a decrease in the early stages (1-2) of ROP in one study. However there were no statistically significant differences in clinically important outcomes including death, growth, BPD, sepsis, ROP ≥ stage 3, and PNALD with the use of newer alternative LE versus the conventional pure soy oil based LE (GRADE QoE ranged from 'low' to 'very low'). Currently there is insufficient evidence to recommend any alternative LE over S-LE or vice versa in preterm infants.Larger randomised studies focusing on important clinical outcomes, targeting specific 'at risk' population subgroups (e.g. extreme prematurity, long term PN, etc), and exploring the effect of different proportions of lipid constituents are required to evaluate the effectiveness of newer lipid emulsions compared with the conventional pure soy based LE in preterm infants.

The combination of electrophysiological recordings with ambiguous visual stimulation made possible the detection of neurons that represent the content of subjective visual perception and perceptual suppression in multiple cortical and subcortical brain regions. These neuronal populations, commonly referred to as the neural correlates of consciousness, are more likely to be found in the temporal and prefrontal cortices as well as the pulvinar, indicating that the content of perceptual awareness is represented with higher fidelity in higher-order association areas of the cortical and thalamic hierarchy, reflecting the outcome of competitive interactions between conflicting sensory information resolved in earlier stages. However, despite the significant insights into conscious perception gained through monitoring the activities of single neurons and small, local populations, the immense functional complexity of the brain arising from correlations in the activity of its constituent parts suggests that local, microscopic activity could only partially reveal the mechanisms involved in perceptual awareness. Rather, the dynamics of functional connectivity patterns on a mesoscopic and macroscopic level could be critical for conscious perception. Understanding these emergent spatio-temporal patterns could be informative not only for the stability of subjective perception but also for spontaneous perceptual transitions suggested to depend either on the dynamics of antagonistic ensembles or on global intrinsic activity fluctuations that may act upon explicit neural representations of sensory stimuli and induce perceptual reorganization. Here, we review the most recent results from local activity recordings and discuss the potential role of effective, correlated interactions during perceptual awareness.

The Middle East respiratory syndrome (MERS) is proposed to be a zoonotic disease; however, the reservoir and mechanism for transmission of the causative agent, the MERS coronavirus, are unknown. Dromedary camels have been implicated through reports that some victims have been exposed to camels, camels in areas where the disease has emerged have antibodies to the virus, and viral sequences have been recovered from camels in association with outbreaks of the disease among humans. Nonetheless, whether camels mediate transmission to humans is unresolved. Here we provide evidence from a geographic and temporal survey of camels in the Kingdom of Saudi Arabia that MERS coronaviruses have been circulating in camels since at least 1992, are distributed countrywide, and can be phylogenetically classified into clades that correlate with outbreaks of the disease among humans. We found no evidence of infection in domestic sheep or domestic goats. IMPORTANCE This study was undertaken to determine the historical and current prevalence of Middle East respiratory syndrome (MERS) coronavirus infection in dromedary camels and other livestock in the Kingdom of Saudi Arabia, where the index case and the majority of cases of MERS have been reported.

A partial purification and biochemical characterization of the α-amylase from Streptomyces sp. MSC702 were carried out in this study. The optimum operational conditions for enzyme substrate reaction for amylolytic enzyme activity from the strain were evaluated. The optimum pH, temperature, and incubation period for assaying the enzyme were observed to be 5.0, 55°C, and 30 min, respectively. The extracellular extract was concentrated using ammonium sulfate precipitation. It was stable in the presence of metal ions (5 mM) such as K(+), Co(2+), and Mo(2+), whereas Pb(2+), Mn(2+), Mg(2+), Cu(2+), Zn(2+), Ba(2+), Ca(2+), Hg(2+), Sn(2+), Cr(3+), Al(3+), Ag(+), and Fe(2+) were found to have inhibitory effects. The enzyme activity was also unstable in the presence of 1% Triton X-100, 1% Tween 80, 5 mM sodium lauryl sulphate, 1% glycerol, 5 mM EDTA, and 5 mM denaturant urea. At temperature 60°C and pH 5.0, the enzyme stability was maximum. α-amylase retained 100% and 34.18% stability for 1 h and 4 h, respectively, at 60°C (pH 7.0). The enzyme exhibited a half-life of 195 min at 60°C temperature. The analysis of kinetic showed that the enzyme has K m of 2.4 mg/mL and V max of 21853.0 μmol/min/mg for soluble potato starch. The results indicate that the enzyme reflects their potentiality towards industrial utilization.

The source of human infection with Middle East respiratory syndrome coronavirus remains unknown. Molecular investigation indicated that bats in Saudi Arabia are infected with several alphacoronaviruses and betacoronaviruses. Virus from 1 bat showed 100% nucleotide identity to virus from the human index case-patient. Bats might play a role in human infection.

Accumulating evidence indicates that control mechanisms are not tightly bound to conscious perception since both conscious and unconscious information can trigger control processes, probably through the activation of higher-order association areas like the prefrontal cortex. Studying the modulation of control-related prefrontal signals in a microscopic, neuronal level during conscious and unconscious neuronal processing, and under control-free conditions could provide an elementary understanding of these interactions. Here we performed extracellular electrophysiological recordings in the macaque lateral prefrontal cortex (LPFC) during monocular physical alternation (PA) and binocular flash suppression (BFS) and studied the local scale relationship between beta (15-30 Hz) oscillations, a rhythmic signal believed to reflect the current sensory, motor, or cognitive state (status-quo), and conscious or unconscious neuronal processing. First, we show that beta oscillations are observed in the LPFC during resting state. Both PA and BFS had a strong impact on the power of this spontaneous rhythm with the modulation pattern of beta power being identical across these two conditions. Specifically, both perceptual dominance and suppression of local neuronal populations in BFS were accompanied by a transient beta desynchronization followed by beta activity rebound, a pattern also observed when perception occurred without any underlying visual competition in PA. These results indicate that under control-free conditions, at least one rhythmic signal known to reflect control processes in the LPFC (i.e., beta oscillations) is not obstructed by local neuronal, and accordingly perceptual, suppression, thus being independent from temporally co-existing conscious and unconscious local neuronal representations. Future studies could reveal the additive effects of motor or cognitive control demands on prefrontal beta oscillations during conscious and unconscious processing.

Understanding the principles that underlie information processing by neuronal networks requires simultaneous recordings from large populations of well isolated single units. Twisted wire tetrodes (TWTs), typically made by winding together four ultrathin wires (diameter: 12-25 μm), are ideally suited for such population recordings. They are advantageous over single electrodes; both with respect to quality of isolation as well as the number of single units isolated and have therefore been used extensively for superficial cortical recordings. However, their limited tensile strength poses a difficulty to their use for recordings in deep brain areas. We therefore developed a method to overcome this limitation and utilize tetrodes for electrophysiological recordings in the inferotemporal cortex of rhesus macaque. We fabricated a novel, stiff tetrode called the tube tetrode (TuTe) and developed a multi-tetrode driving system for advancing up to 5 TuTes through a ball and socket chamber to precise locations in the temporal lobe of a rhesus macaque. The signal quality acquired with TuTes was comparable to conventional TWTs and allowed excellent isolation of multiple single units. We describe here a simple method for constructing TuTes, which requires only standard laboratory equipment. Further, our TuTes can be easily adapted to work with other microdrives commonly used for electrophysiological investigation in the macaque brain and produce minimal damage to the cortex along its path because of their ultrathin diameter. The tetrode development described here could allow studying neuronal populations in deep lying brain structures previously difficult to reach with the current technology., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The neural correlates of conscious visual perception are commonly studied in paradigms of perceptual multistability that allow multiple perceptual interpretations during unchanged sensory stimulation. What is the source of this multistability in the content of perception? From a theoretical perspective, a fine balance between deterministic and stochastic forces has been suggested to underlie the spontaneous, intrinsically driven perceptual transitions observed during multistable perception. Deterministic forces are represented by adaptation of feature-selective neuronal populations encoding the competing percepts while stochastic forces are modeled as noise-driven processes. Here, we used a unified neuronal competition model to study the dynamics of adaptation and noise processes in binocular flash suppression (BFS), a form of externally induced perceptual suppression, and compare it with the dynamics of intrinsically driven alternations in binocular rivalry (BR). For the first time, we use electrophysiological, biologically relevant data to constrain a model of perceptual rivalry. Specifically, we show that the mean population discharge pattern of a perceptually modulated neuronal population detected in electrophysiological recordings in the lateral prefrontal cortex (LPFC) during BFS, constrains the dynamical range of externally induced perceptual transitions to a region around the bifurcation separating a noise-driven attractor regime from an adaptation-driven oscillatory regime. Most interestingly, the dynamical range of intrinsically driven perceptual transitions during BR is located in the noise-driven attractor regime, where it overlaps with BFS. Our results suggest that the neurodynamical mechanisms of externally induced and spontaneously generated perceptual alternations overlap in a narrow, noise-driven region just before a bifurcation where the system becomes adaptation-driven.

Agro-industrial wastes such as sugarcane bagasse, wheat bran, rice bran, corn cob and wheat straw are cheapest and abundantly available natural carbon sources. The present study was aimed to production of amylase and xylanase simultaneously using agro-industrial waste as the sole carbon source. Seven thermophilic strains of actinomycete were isolated from the mushroom compost. Among of these, strain designated MSC702 having high potential to utilize agro-industrial wastes for the production of amylase and xylanase. Strain MSC702 was identified as novel species of Streptomyces through morphological characterization and 16S rRNA gene sequence. Enzyme production was determined using 1% (w/v) of various agro-industrial waste in production medium containing (g/100mL): K2HPO4 (0.1), (NH4)2SO4 (0.1), NaCl (0.1), MgSO4 (0.1) at pH 7.0 after incubation of 48 h at 50°C. The amylase activity (373.89 IU/mL) and xylanase activity (30.15 IU/mL) was maximum in rice bran. The decreasing order of amylase and xylanase activity in different type of agro-industrial wastes were found rice bran (RB) > corn cob (CC) > wheat bran (WB) > wheat straw (WS) > sugarcane bagasse (SB) and rice bran (RB) > wheat bran (WB) > wheat straw (WS) > sugarcane bagasse (SB) > corn cob (CC), respectively. Mixed effect of different agro-industrial wastes was examined in different ratios. Enzyme yield of amylase and xylanase was ~1.3 and ~2.0 fold higher with RB: WB in 1:2 ratio.

Neuronal discharges in the primate temporal lobe, but not in the striate and extrastriate cortex, reliably reflect stimulus awareness. However, it is not clear whether visual consciousness should be uniquely localized in the temporal association cortex. Here we used binocular flash suppression to investigate whether visual awareness is also explicitly reflected in feature-selective neural activity of the macaque lateral prefrontal cortex (LPFC), a cortical area reciprocally connected to the temporal lobe. We show that neuronal discharges in the majority of single units and recording sites in the LPFC follow the phenomenal perception of a preferred stimulus. Furthermore, visual awareness is reliably reflected in the power modulation of high-frequency (>50 Hz) local field potentials in sites where spiking activity is found to be perceptually modulated. Our results suggest that the activity of neuronal populations in at least two association cortical areas represents the content of conscious visual perception., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Perceptual bistability arises when two conflicting interpretations of an ambiguous stimulus or images in binocular rivalry (BR) compete for perceptual dominance. From a computational point of view, competition models based on cross-inhibition and adaptation have shown that noise is a crucial force for rivalry, and operates in balance with adaptation. In particular, noise-driven transitions and adaptation-driven oscillations define two dynamical regimes and the system explains the observed alternations in perception when it operates near their boundary. In order to gain insights into the microcircuit dynamics mediating spontaneous perceptual alternations, we used a reduced recurrent attractor-based biophysically realistic spiking network, well known for working memory, attention, and decision making, where a spike-frequency adaptation mechanism is implemented to account for perceptual bistability. We thus derived a consistently reduced four-variable population rate model using mean-field techniques, and we tested it on BR data collected from human subjects. Our model accounts for experimental data parameters such as mean time dominance, coefficient of variation, and gamma distribution fit. In addition, we show that our model operates near the bifurcation that separates the noise-driven transitions regime from the adaptation-driven oscillations regime, and agrees with Levelt's second revised and fourth propositions. These results demonstrate for the first time that a consistent reduction of a biophysically realistic spiking network of leaky integrate-and-fire neurons with spike-frequency adaptation could account for BR. Moreover, we demonstrate that BR can be explained only through the dynamics of competing neuronal pools, without taking into account the adaptation of inhibitory interneurons. However, the adaptation of interneurons affects the optimal parametric space of the system by decreasing the overall adaptation necessary for the bifurcation to occur, and introduces oscillations in the spontaneous state.

How the brain maintains perceptual continuity across eye movements that yield discontinuous snapshots of the world is still poorly understood. In this study, we adapted a framework from the dual-task paradigm, well suited to reveal bottlenecks in mental processing, to study how information is processed across sequential saccades. The pattern of RTs allowed us to distinguish among three forms of trans-saccadic processing (no trans-saccadic processing, trans-saccadic visual processing and trans-saccadic visual processing and saccade planning models). Using a cued double-step saccade task, we show that even though saccade execution is a processing bottleneck, limiting access to incoming visual information, partial visual and motor processing that occur prior to saccade execution is used to guide the next eye movement. These results provide insights into how the oculomotor system is designed to process information across multiple fixations that occur during natural scanning.

Background and Aim: The World Health Organization recommends oral zinc (tablets or syrups) as adjunct therapy with oral rehydration solution (ORS) for acute childhood diarrhea. Mixing zinc with ORS can be an attractive approach for simultaneous provision of these 2 effective interventions. This double-masked randomized controlled trial evaluated the efficacy of ORS containing 40  mg/L elemental zinc per liter (zinc-ORS) in reducing stool weight and duration of diarrhea., Patients and Methods: Five hundred northern Indian children ages 1 to 35 months with diarrhea <7 days' duration were randomized to zinc-ORS or ORS. The primary outcomes were total stool output and time to recovery., Results: The median total stool output was 2.12 g · kg⁻¹ · h⁻¹ (interquartile range [IQR] 0.9-3.76) in the zinc-ORS group compared with 1.78 g · kg⁻¹ · h⁻¹ (IQR 0.83-3.45) in the ORS group. The time to recovery was also similar in the 2 groups (hazard ratio 1.06 [95% confidence interval 0.88-1.27]). In subjects who received zinc-ORS, the median (IQR) zinc intakes were 27 (16-46) mg on day 1, 15 (6-27) mg on day 2, and negligible thereafter., Conclusions: The World Health Organization-recommended daily dose of zinc for diarrhea was not achieved in most children beyond the first day of treatment. This is the likely explanation for the lack of improvement in outcomes from zinc-ORS when compared with ORS alone. Our findings do not support a change from using zinc syrup or dispersible tablets for treatment of acute diarrhea in children.

Background: We performed a longitudinal study of viral etiology in samples collected in New York City during May 2009 to May 2010 from outpatients with fever or respiratory disease symptoms in the context of a pilot respiratory virus surveillance system., Methods: Samples were assessed for the presence of 13 viruses, including influenza A virus, by MassTag PCR., Results: At least one virus was detected in 52% of 940 samples analyzed, with 3% showing co-infections. The most frequently detected agents were rhinoviruses and influenza A, all representing the 2009 pandemic H1N1 strain. The incidence of influenza H1N1-positive samples was highest in late spring 2009, followed by a decline in summer and early fall, when rhinovirus infections became predominant before H1N1 reemerged in winter. Our study also identified a focal outbreak of enterovirus 68 in the early fall of 2009., Conclusion: MassTag multiplex PCR affords opportunities to track the epidemiology of infectious diseases and may guide clinicians and public health practitioners in influenza-like illness and outbreak management. Nonetheless, a substantial proportion of influenza-like illness remains unexplained underscoring the need for additional platforms.

Background: Initial reports in May 2009 of the novel influenza strain H1N1pdm estimated a case fatality rate (CFR) of 0.6%, similar to that of seasonal influenza. In July 2009, however, Argentina reported 3056 cases with 137 deaths, representing a CFR of 4.5%. Potential explanations for increased CFR included virus reassortment or genetic drift, or infection of a more vulnerable population. Virus genomic sequencing of 26 Argentinian samples representing both severe and mild disease indicated no evidence of reassortment, mutations associated with resistance to antiviral drugs, or genetic drift that might contribute to virulence. Furthermore, no evidence was found for increased frequency of risk factors for H1N1pdm disease., Methods/principal Findings: We examined nasopharyngeal swab samples (NPS) from 199 cases of H1N1pdm infection from Argentina with MassTag PCR, testing for 33 additional microbial agents. The study population consisted of 199 H1N1pdm-infected subjects sampled between 23 June and 4 July 2009. Thirty-nine had severe disease defined as death (n = 20) or hospitalization (n = 19); 160 had mild disease. At least one additional agent of potential pathogenic importance was identified in 152 samples (76%), including Streptococcus pneumoniae (n = 62); Haemophilus influenzae (n = 104); human respiratory syncytial virus A (n = 11) and B (n = 1); human rhinovirus A (n = 1) and B (n = 4); human coronaviruses 229E (n = 1) and OC43 (n = 2); Klebsiella pneumoniae (n = 2); Acinetobacter baumannii (n = 2); Serratia marcescens (n = 1); and Staphylococcus aureus (n = 35) and methicillin-resistant S. aureus (MRSA, n = 6). The presence of S. pneumoniae was strongly correlated with severe disease. S. pneumoniae was present in 56.4% of severe cases versus 25% of mild cases; more than one-third of H1N1pdm NPS with S. pneumoniae were from subjects with severe disease (22 of 62 S. pneumoniae-positive NPS, p = 0.0004). In subjects 6 to 55 years of age, the adjusted odds ratio (OR) of severe disease in the presence of S. pneumoniae was 125.5 (95% confidence interval [CI], 16.95, 928.72; p<0.0001)., Conclusions/significance: The association of S. pneumoniae with morbidity and mortality is established in the current and previous influenza pandemics. However, this study is the first to demonstrate the prognostic significance of non-invasive antemortem diagnosis of S. pneumoniae infection and may provide insights into clinical management.

MassTag polymerase chain reaction (PCR) is a platform that enables microbe detection using primers labeled through a photocleavable link with tags that vary in molecular weight. After multiplex PCR, tags are released by ultraviolet irradiation and analyzed by mass spectroscopy. The identification of a microbe in a sample is determined by its cognate tags. Here we describe establishment and implementation of a MassTag PCR panel for surveillance of microbes implicated in tick-vectored infectious diseases.

Background: Respiratory infections are the most common infectious diseases in humans worldwide and are a leading cause of death in children less than 5 years of age., Objectives: Identify candidate pathogens in pediatric patients with unexplained respiratory disease., Study Design: Forty-four nasopharyngeal washes collected during the 2004-2005 winter season from pediatric patients with respiratory illnesses that tested negative for 7 common respiratory pathogens by culture and direct immunofluorescence assays were analyzed by MassTag-PCR. To distinguish human enteroviruses (HEV) and rhinoviruses (HRV), samples positive for picornaviruses were further characterized by sequence analysis., Results: Candidate pathogens were detected by MassTag PCR in 27 of the 44 (61%) specimens that previously were rated negative. Sixteen of these 27 specimens (59%) contained picornaviruses; of these 9 (57%) contained RNA of a recently discovered clade of rhinoviruses. Bocaviruses were detected in three patients by RT-PCR., Conclusions: Our study confirms that multiplex MassTag-PCR enhances the detection of pathogens in clinical specimens, and shows that previously unrecognized rhinoviruses, that potentially form a species HRV-C, may cause a significant amount of pediatric respiratory disease.

Staphylococcus aureus can cause a spectrum of exfoliative skin conditions including staphylococcal scalded skin syndrome (SSSS) which can present as a severe and life threatening illness in extremely premature neonates. We describe a case of an extremely premature neonate with SSSS and discuss relevant pathology and issues in clinical management.

Global surveillance for a novel rhinovirus genotype indicated its association with community outbreaks and pediatric respiratory disease in Africa, Asia, Australia, Europe, and North America. Molecular dating indicates that these viruses have been circulating for at least 250 years.

A planned action awaiting execution requires withholding a prepared response. We asked whether such a form of inhibition would interact with online decision processes that require changes in planned responses when new goals are unexpectedly specified. To investigate this issue with respect to oculomotor control, subjects performed, in separate sessions, standard visually-guided (SV) saccades, or memory-guided (MG) and delayed visually-guided (DV) saccades, both of which required withholding a planned saccade. To probe control, a second target (target-step) was presented in some trials after a variable delay that instructed subjects to redirect their gaze to the newly specified target. The time taken to cancel or inhibit the saccade directed at the initial target, the target step reaction time, was calculated using a race model that hypothesizes a covert inhibitory process, and was found to be significantly smaller for memory-guided redirect task (MGR; 94 ms) and delayed visually-guided redirect task (DVR; 96 ms) compared to standard visually-guided redirect task (SVR; 117 ms), suggesting facilitation of online inhibition in MGR and DVR. These results suggest that a tonic level of inhibition interacts with online decision processes to potentiate inhibitory control during double-step tasks.

Acute respiratory infection is a significant cause of morbidity and mortality in children worldwide. Accurate identification of causative agents is critical to case management and to prioritization in vaccine development. Sensitive multiplex diagnostics provide us with an opportunity to investigate the relative contributions of individual agents and may also facilitate the discovery of new pathogens. Recently, application of MassTag polymerase chain reaction (PCR) to undiagnosed influenza-like illness in New York State led to the discovery of a novel rhinovirus genotype. Here we report the investigation, by MassTag PCR, of pediatric respiratory-tract infections in Germany, studying 97 cases for which no pathogen was identified through routine laboratory evaluation. Respiratory viruses were identified in 49 cases (51%); of the 55 identified viruses, 41 (75%) were rhinoviruses. The novel genotype represented 73% of rhinoviruses and 55% of all identified viruses. Infections with the novel genotype were associated with upper-respiratory-tract symptoms but, more frequently, with bronchitis, bronchiolitis, and pneumonia.