Maze solvers demystified and some other thoughts

There is a growing interest towards implementation of maze solving in spatially-extended physical, chemical and living systems. Several reports of prototypes attracted great publicity, e.g. maze solving with slime mould and epithelial cells, maze navigating droplets. We show that most prototypes utilise one of two phenomena: a shortest path in a maze is a path of the least resistance for fluid and current flow, and a shortest path is a path of the steepest gradient of chemoattractants. We discuss that substrates with so-called maze-solving capabilities simply trace flow currents or chemical diffusion gradients. We illustrate our thoughts with a model of flow and experiments with slime mould. The chapter ends with a discussion of experiments on maze solving with plant roots and leeches which show limitations of the chemical diffusion maze-solving approach.Comment: This is a preliminary version of the chapter to be published in Adamatzky A. (Ed.) Shortest path solvers. From software to wetware. Springer, 201

Prescription Drugs Associated with Reports of Violence Towards Others

CONTEXT: Violence towards others is a seldom-studied adverse drug event and an atypical one because the risk of injury extends to others. OBJECTIVE: To identify the primary suspects in adverse drug event reports describing thoughts or acts of violence towards others, and assess the strength of the association. METHODOLOGY: From the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS) data, we extracted all serious adverse event reports for drugs with 200 or more cases received from 2004 through September 2009. We identified any case report indicating homicide, homicidal ideation, physical assault, physical abuse or violence related symptoms. MAIN OUTCOME MEASURES: Disproportionality in reporting was defined as a) 5 or more violence case reports, b) at least twice the number of reports expected given the volume of overall reports for that drug, c) a χ2 statistic indicating the violence cases were unlikely to have occurred by chance (p<0.01). RESULTS: We identified 1527 cases of violence disproportionally reported for 31 drugs. Primary suspect drugs included varenicline (an aid to smoking cessation), 11 antidepressants, 6 sedative/hypnotics and 3 drugs for attention deficit hyperactivity disorder. The evidence of an association was weaker and mixed for antipsychotic drugs and absent for all but 1 anticonvulsant/mood stabilizer. Two or fewer violence cases were reported for 435/484 (84.7%) of all evaluable drugs suggesting that an association with this adverse event is unlikely for these drugs. CONCLUSIONS: Acts of violence towards others are a genuine and serious adverse drug event associated with a relatively small group of drugs. Varenicline, which increases the availability of dopamine, and antidepressants with serotonergic effects were the most strongly and consistently implicated drugs. Prospective studies to evaluate systematically this side effect are needed to establish the incidence, confirm differences among drugs and identify additional common features

Characterisation of gastroenteritis associated adenoviruses in South Africa

Objective. To analyse adenovirus (Ad) numbers and types associated with paediatric gastro-enteritis in South AfricaSetting. Gauteng, 1994-1996.Methods. A total of 234 paediatric diarrhoeal stool samples were screened for Ad using commercial enzyme-linked iInmunosorbent assays (EUSAs). Adenoviral isolates were typed, where possibie, using restriction enzyme analysis.Results. Ad was detected in 23 (9.8%) specimens, of which 8 (34.8%) were found by subgroup F-specilic EUSA to contain Ad40 or 41. Six of these isolates were typed and 2 could not be typed. Of the remaining 15 specimens, 2 isolates had restriction profiles that did not correspond with known Ads, while 2were identified as Ad31 and 1 as a subgroup CAd. The remaining 10 specimens negative for Ad40/41 were noncultivable and could not be typed.Conclusions. The high percentage of non-eultivable Ads other than Ad40/41 is unusual, and may possibly indicate the prevalence of hexon variants of Ad40/41 or of emerging Ad types in South Africa

Prevalence and Antimicrobial Resistance of Bacteria in Children With Acute Otitis Media and Ear Discharge: A Systematic Review.

BACKGROUND: Of children with acute otitis media (AOM), 15%-20% present with acute onset ear discharge due to a spontaneous perforation of the tympanic membrane (AOMd). This review aims to quantify the prevalence and antimicrobial resistance (AMR) status of bacteria in children with AOMd in the pneumococcal conjugate vaccine (PCV) era. METHODS: Systematic searches were performed in PubMed, EMBASE and Cochrane Library from inception to June 7, 2019. Two reviewers extracted relevant data and assessed risk of bias independently. All English studies reporting any prevalence and/or AMR data of bacterial middle ear isolates from children with AOMd were included. Risk of bias was assessed using the Joanna Briggs Institute Critical Appraisal checklist. RESULTS: Of 4088 unique records retrieved, 19 studies (10,560 children) were included. Overall quality was judged good. Streptococcus pneumoniae (median 26.1%, range 9.1%-47.9%), Haemophilus influenzae (median 18.8%, range 3.9%-55.3%), Staphylococcus aureus (median 12.3%, range 2.3%-34.9%) and Streptococcus pyogenes (median 11.8%, range 1.0%-30.9%) were the most prevalent bacteria. In 76.0% (median, range 48.7%-100.0%, 19 studies, 1,429 children) any bacterium was identified. AMR data were sparse and mainly limited to S. pneumoniae. We found no evidence of a clear shift in the prevalence of bacteria and AMR over time. CONCLUSIONS: In children with AOMd, S. pneumoniae and H. influenzae are the 2 predominant bacteria, followed by S. aureus and S. pyogenes in the post-PCV era. AMR data are sparse and no clearly change over time was observed. Ongoing surveillance of the microbiology profile in children with AOMd is warranted to guide antibiotic selection and to assess the impact of children's PCV status

Weathering the storm: parental effort and experimental manipulation of stress hormones predict brood survival

BACKGROUND:Unpredictable and inclement weather is increasing in strength and frequency, challenging organisms to respond adaptively. One way in which animals respond to environmental challenges is through the secretion of glucocorticoid stress hormones. These hormones mobilize energy stores and suppress non-essential physiological and behavioral processes until the challenge passes. To investigate the effects of glucocorticoids on reproductive decisions, we experimentally increased corticosterone levels (the primary glucocorticoid in birds) in free-living female tree swallows, Tachycineta bicolor, during the chick-rearing stage. Due to an unprecedented cold and wet breeding season, 90% of the nests in our study population failed, which created a unique opportunity to test how challenging environmental conditions interact with the physiological mechanisms underlying life-history trade-offs.RESULTS:We found that exogenous corticosterone influenced the regulation of parental decisions in a context-dependent manner. Control and corticosterone-treated females had similar brood failure rates under unfavorable conditions (cold and rainy weather), but corticosterone treatment hastened brood mortality under more favorable conditions. Higher female nest provisioning rates prior to implantation were associated with increased probability of brood survival for treatment and control groups. However, higher pre-treatment male provisioning rates were associated with increased survival probability in the control group, but not the corticosterone-treated group.CONCLUSIONS:These findings reveal complex interactions between weather, female physiological state, and partner parental investment. Our results also demonstrate a causal relationship between corticosterone concentrations and individual reproductive behaviors, and point to a mechanism for why naturally disturbed populations, which experience multiple stressors, could be more susceptible and unable to respond adaptively to changing environmental conditions

Effect of universal MODS access on pulmonary tuberculosis treatment outcomes in new patients in Peru.

SETTING: Primary health care centres in Callao, Peru. OBJECTIVES: To evaluate the effect of universal access to the microscopic-observation drug susceptibility (MODS) assay on treatment outcomes in new and primary multidrug-resistant tuberculosis (MDR-TB) patients and on the process of drug susceptibility testing (DST). DESIGN: Retrospective review of tuberculosis (TB) registers and clinical records before (2007) and after (2009) the introduction of MODS in 2008. RESULTS: There were 281 patients in each cohort. Favourable treatment outcomes for 2007 (81%) and 2009 (77%) cohorts were similar. There was an increase in loss to follow-up (from 6% to 10%, P = 0.04) and a reduction in failure rates (from 4% to 0.4%, P = 0.01) in the 2009 compared with the 2007 cohort. In new MDR-TB cases (n = 22), a favourable treatment outcome was improved (from 46% to 82%, P = 0.183) in the 2009 cohort. DST coverage improved (from 24% to 74%, P < 0.001), and a significant reduction in time to diagnosis of drug-susceptible (from 118 to 33 days, P < 0.001) and MDR-TB (from 158 to 52 days, P =30.003) was observed in the 2009 cohort. CONCLUSION: Universal access to MODS increased DST coverage, reduced the time required to obtain DST results and was associated with reduced failure rates. MODS can make an important contribution to TB management and control in Peru

AMPK and uterine artery vasodilation

Genes near adenosine monophosphate-activated protein kinase-α1 (PRKAA1) have been implicated in the greater uterine artery (UtA) blood flow and relative protection from fetal growth restriction seen in altitude-adapted Andean populations. Adenosine monophosphate-activated protein kinase (AMPK) activation vasodilates multiple vessels but whether AMPK is present in UtA or placental tissue and influences UtA vasoreactivity during normal or hypoxic pregnancy remains unknown. We studied isolated UtA and placenta from near-term C57BL/6J mice housed in normoxia (n = 8) or hypoxia (10% oxygen, n = 7-9) from day 14 to day 19, and placentas from non-labouring sea level (n = 3) or 3100 m (n = 3) women. Hypoxia increased AMPK immunostaining in near-term murine UtA and placental tissue. RT-PCR products for AMPK-α1 and -α2 isoforms and liver kinase B1 (LKB1; the upstream kinase activating AMPK) were present in murine and human placenta, and hypoxia increased LKB1 and AMPK-α1 and -α2 expression in the high- compared with low-altitude human placentas. Pharmacological AMPK activation by A769662 caused phenylephrine pre-constricted UtA from normoxic or hypoxic pregnant mice to dilate and this dilatation was partially reversed by the NOS inhibitor l-NAME. Hypoxic pregnancy sufficient to restrict fetal growth markedly augmented the UtA vasodilator effect of AMPK activation in opposition to PE constriction as the result of both NO-dependent and NO-independent mechanisms. We conclude that AMPK is activated during hypoxic pregnancy and that AMPK activation vasodilates the UtA, especially in hypoxic pregnancy. AMPK activation may be playing an adaptive role by limiting cellular energy depletion and helping to maintain utero-placental blood flow in hypoxic pregnancy.Funding for these studies was provided by the Wellcome Trust (084804/2/08/Z) to G.J.B., the British Heart Foundation and the Wellcome Trust to D.A.G., the Biotechnology and Biological Sciences Research Council (BBSRC) to A.L.F., a UK Wellcome Trust Programme Grant (WT081195MA) to A.M.E. and A.D.M., a BBSRC studentship and in vivo skills award to J.S.H., a National Health Medical Research Council and Centre for Trophoblast Research fellowship to A.N.S.-P., and a NIH RO1 grant (HLBI-079647) to L.G.M. along with sabbatical support from Wake Forest University.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1113/JP27099

Predicting illness progression for children with lower respiratory infections (LRTI) presenting to primary care

Background Antibiotics are commonly prescribed for children with lower respiratory tract infections (LRTIs), fuelling antibiotic resistance, and there are few prognostic tools available to inform management. Aim To externally validate an existing prognostic model (STARWAVe) to identify children at low risk of illness progression, and if model performance was limited to develop a new internally validated prognostic model. Design and setting Prospective cohort study with a nested trial in a primary care setting. Method Children aged 6 months to 12 years presenting with uncomplicated LRTI were included in the cohort. Children were randomised to receive amoxicillin 50 mg/kg per day for 7 days or placebo, or if not randomised they participated in a parallel observational study to maximise generalisability. Baseline clinical data were used to predict adverse outcome (illness progression requiring hospital assessment). Results A total of 758 children participated (n= 432 trial, n= 326 observational). For predicting illness progression the STARWAVe prognostic model had moderate performance (area under the receiver operating characteristic [AUROC] 0.66, 95% confidence interval [CI] = 0.50 to 0.77), but a new, internally validated model (seven items: baseline severity; respiratory rate; duration of prior illness; oxygen saturation; sputum or a rattly chest; passing urine less often; and diarrhoea) had good discrimination (bootstrapped AUROC 0.83, 95% CI = 0.74 to 0.92) and calibration. A three-item model (respiratory rate; oxygen saturation; and sputum or a rattly chest) also performed well (AUROC 0.81, 95% CI = 0.70 to 0.91), as did a score (ranging from 19 to 102) derived from coefficients of the model (AUROC 0.78, 95% CI = 0.67 to 0.88): a score of &lt;70 classified 89% (n= 600/674) of children having a low risk (&lt;5%) of progression of illness. Conclusion A simple three-item prognostic score could be useful as a tool to identify children with LRTI who are at low risk of an adverse outcome and to guide clinical management.</p

Early and efficient detection of Mycobacterium tuberculosis in sputum by microscopic observation of broth cultures.

Early, efficient and inexpensive methods for the detection of pulmonary tuberculosis are urgently needed for effective patient management as well as to interrupt transmission. These methods to detect M. tuberculosis in a timely and affordable way are not yet widely available in resource-limited settings. In a developing-country setting, we prospectively evaluated two methods for culturing and detecting M. tuberculosis in sputum. Sputum samples were cultured in liquid assay (micro broth culture) in microplate wells and growth was detected by microscopic observation, or in Löwenstein-Jensen (LJ) solid media where growth was detected by visual inspection for colonies. Sputum samples were collected from 321 tuberculosis (TB) suspects attending Bugando Medical Centre, in Mwanza, Tanzania, and were cultured in parallel. Pulmonary tuberculosis cases were diagnosed using the American Thoracic Society diagnostic standards. There were a total of 200 (62.3%) pulmonary tuberculosis cases. Liquid assay with microscopic detection detected a significantly higher proportion of cases than LJ solid culture: 89.0% (95% confidence interval [CI], 84.7% to 93.3%) versus 77.0% (95% CI, 71.2% to 82.8%) (p = 0.0007). The median turn around time to diagnose tuberculosis was significantly shorter for micro broth culture than for the LJ solid culture, 9 days (interquartile range [IQR] 7-13), versus 21 days (IQR 14-28) (p<0.0001). The cost for micro broth culture (labor inclusive) in our study was US $4.56 per sample, versus US$11.35 per sample for the LJ solid culture. The liquid assay (micro broth culture) is an early, feasible, and inexpensive method for detection of pulmonary tuberculosis in resource limited settings

Observation of spin Coulomb drag in a two-dimensional electron gas

An electron propagating through a solid carries spin angular momentum in addition to its mass and charge. Of late there has been considerable interest in developing electronic devices based on the transport of spin, which offer potential advantages in dissipation, size, and speed over charge-based devices. However, these advantages bring with them additional complexity. Because each electron carries a single, fixed value (-e) of charge, the electrical current carried by a gas of electrons is simply proportional to its total momentum. A fundamental consequence is that the charge current is not affected by interactions that conserve total momentum, notably collisions among the electrons themselves. In contrast, the electron's spin along a given spatial direction can take on two values, "up" and "down", so that the spin current and momentum need not be proportional. Although the transport of spin polarization is not protected by momentum conservation, it has been widely assumed that, like the charge current, spin current is unaffected by electron-electron (e-e) interactions. Here we demonstrate experimentally not only that this assumption is invalid, but that over a broad range of temperature and electron density, the flow of spin polarization in a two-dimensional gas of electrons is controlled by the rate of e-e collisions