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To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants.
Before-and-after intervention study.
Tertiary-care children’s hospital.
Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED).
The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis.
Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29–60 days old being managed without antibiotics.
Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.
Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.
To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.
Participants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.
Youth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.
Suicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.
Declaration of interest
R.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.
Liquid water on Mars might be created by deliquescence of hygroscopic salts or by permafrost melts, both potentially forming saturated brines. Freezing point depression allows these heavy brines to remain liquid in the near-surface environment for extended periods, perhaps as eutectic solutions, at the lowest temperatures and highest salt concentrations where ices and precipitates do not form. Perchlorate and chlorate salts and iron sulphate form brines with low eutectic temperatures and may persist under Mars near-surface conditions, but are chemically harsh at high concentrations and were expected to be incompatible with life, while brines of common sulphate salts on Mars may be more suitable for microbial growth. Microbial growth in saturated brines also may be relevant beyond Mars, to the oceans of Ceres, Enceladus, Europa and Pluto. We have previously shown strong growth of salinotolerant bacteria in media containing 2M MgSO4 heptahydrate (~50% w/v) at 25°C. Here we extend those observations to bacterial isolates from Basque Lake, BC and Hot Lake, WA, that grow well in saturated MgSO4 medium (67%) at 25°C and in 50% MgSO4 medium at 4°C (56% would be saturated). Psychrotolerant, salinotolerant microbes isolated from Basque Lake soils included Halomonas and Marinococcus, which were identified by 16S rRNA gene sequencing and characterized phenetically. Eutectic liquid medium constituted by 43% MgSO4 at −4°C supported copious growth of these psychrotolerant Halomonas isolates, among others. Bacterial isolates also grew well at the eutectic for K chlorate (3% at −3°C). Survival and growth in eutectic solutions increases the possibility that microbes contaminating spacecraft pose a contamination risk to Mars. The cold brines of sulphate and (per)chlorate salts that may form at times on Mars through deliquescence or permafrost melt have now been demonstrated to be suitable microbial habitats, should appropriate nutrients be available and dormant cells become vegetative.
Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample.
The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8–21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009–2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered.
Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized β = .378); psychosis spectrum (β = .360); externalizing behaviors (β = .311); and fear (β = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition.
Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.
Four complete platysiagid fish specimens are described from the Luoping Biota, Anisian (Middle Triassic), Yunnan Province, southwest China. They are small fishes with bones and scales covered with ganoine. All characters observed, such as nasals meeting in the midline, a keystone-like dermosphenotic, absence of post-rostral bone, two infraorbitals between dermosphenotic and jugal, large antorbital, and two postcleithra, suggest that the new materials belong to a single, new Platysiagum species, P. sinensis sp. nov. Three genera are ascribed to Platysiagidae: Platysiagum, Helmolepis and Caelatichthys. However, most specimens of the first two genera are imprints or fragmentary. The new, well-preserved specimens from the Luoping Biota provide more detailed anatomical information than before, and thus help amend the concept of the Platysiagidae. The Family Platysiagidae was previously classed in the Perleidiformes. Phylogenetic analysis indicates that the Platysiagidae is a member of basal Neopterygii, and its origin seems to predate that of Perleidiformes. Moreover, platysiagid fishes are known from the Middle Triassic of the western Tethys region. The newly found specimens of platysiagids from Luoping provide additional evidence that both eastern and western sides of the Tethys Ocean were biogeographically more connected than previously thought.
The Phoenix lander at Mars polar cap found appreciable levels of (per)chlorate salts, a mixture of perchlorate and chlorate salts of Ca, Fe, Mg and Na at levels of ~0.6% in regolith. These salts are highly hygroscopic and can form saturated brines through deliquescence, likely producing aqueous solutions with very low freezing points on Mars. To support planetary protection efforts, we have measured bacterial growth tolerance to (per)chlorate salts. Existing bacterial isolates from the Great Salt Plains of Oklahoma (NaCl-rich) and Hot Lake in Washington (MgSO4-rich) were tested in high concentrations of Mg, K and Na salts of chlorate and perchlorate. Strong growth was observed with nearly all of these salinotolerant isolates at 1% (~0.1 M) (per)chlorate salts, similar to concentrations observed in bulk soils on Mars. Growth in perchlorate salts was observed at concentrations of at least 10% (~1.0 M). Greater tolerance was observed for chlorate salts, where growth was observed to 2.75 M (>25%). Tolerance to K salts was greatest, followed by Mg salts and then Na salts. Tolerances varied among isolates, even among those within the same phylogenetic clade. Tolerant bacteria included genera that also are found in spacecraft assembly facilities. Substantial microbial tolerance to (per)chlorate salts is a concern for planetary protection since tolerant microbes contaminating spacecraft would have a greater chance for survival and proliferation, despite the harsh chemical conditions found near the surface of Mars.
The most extremely osmotolerant microbial isolates are fungi from high-sugar environments that tolerate the lowest water activity (0.61) for growth yet reported. Studies of osmotolerant bacteria have focused on halotolerance rather than sucretolerance (ability to grow in high sugar concentrations). A collection of salinotolerant (≥10% NaCl or ≥50% MgSO4) bacterial isolates from the Great Salt Plains of Oklahoma and Hot Lake in Washington were screened for sucretolerance in medium supplemented with ≥50% fructose, glucose or sucrose. Tolerances significantly differed between solutes, even though water activities for saline media (0.92 and 0.85 for 10 and 20% NaCl Salt Plains media, respectively) were comparable or lower than water activities for high-sugar media (0.93 and 0.90 for 50 and 70% sucrose artificial nectar media, respectively). These specific solute effects were differentially expressed among individual isolates. Extrapolating the results of earlier food science studies with yeasts at high sugar concentrations to bacteria in salty environments with low water activity should be done with caution. Furthermore, the discussion of habitable Special Regions on Mars and the icy worlds should reflect an understanding of specific solute effects.
Various Mars missions have detected Cl atoms, chlorides and perchlorates in martian surface materials. The global soils, in particular, always contain significant levels of observable Cl. Direct evidence points to this Cl being in the form of both chlorides and perchlorates, and possibly also chlorates and other oxychlorines. The most widespread measurements have been of Cl atoms, and cannot discern the chemical form. However, from separate evidence of perchlorate obtained at high latitudes (Phoenix lander) and low latitudes (Curiosity rover), it is likely that perchlorates are widespread, albeit in varying proportions relative to the total amount of ubiquitous Cl.
Hot Lake (Oroville, WA) is an athalassohaline epsomite lake that can have precipitating concentrations of MgSO4 salts, mainly epsomite. Little biotic study has been done on epsomite lakes and it was unclear whether microbes isolated from epsomite lakes and their margins would fall within recognized halotolerant genera, common soil genera or novel phyla. Our initial study cultivated and characterized epsotolerant bacteria from the lake and its margins. Approximately 100 aerobic heterotrophic microbial isolates were obtained by repetitive streak-plating in high-salt media including either 10% NaCl or 2 M MgSO4. The collected isolates were all bacteria, nearly evenly divided between Gram-positive and Gram-negative clades, the most abundant genera being Halomonas, Idiomarina, Marinobacter, Marinococcus, Nesterenkonia, Nocardiopsis and Planococcus. Bacillus, Corynebacterium, Exiguobacterium, Kocuria and Staphylococcus also were cultured. This initial study included culture-independent community analysis of direct DNA extracts of lake margin soil using PCR-based clone libraries and 16S rRNA gene phylogeny. Clones assigned to Gram-positive bacterial clades (70% of total clones) were dominated by sequences related to uncultured actinobacteria. There were abundant Deltaproteobacteria clones related to bacterial sulphur metabolisms and clones of Legionella and Coxiella. These epsomite lake microbial communities seem to be divided between bacteria primarily associated with hyperhaline environments rich in NaCl and salinotolerant relatives of common soil organisms. Archaea appear to be in low abundance and none were isolated, despite near-saturated salinities. Growth of microbes at very high concentrations of magnesium and other sulphates has relevance to planetary protection and life-detection missions to Mars, where scant liquid water may form as deliquescent brines and appear as eutectic liquids.
The rise of archosaurs during the Triassic and Early Jurassic has been treated as a classic example of an evolutionary radiation in the fossil record. This paper reviews published studies and provides new data on archosaur lineage origination, diversity and lineage evolution, morphological disparity, rates of morphological character change, and faunal abundance during the Triassic–Early Jurassic. The fundamental archosaur lineages originated early in the Triassic, in concert with the highest rates of character change. Disparity and diversity peaked later, during the Norian, but the most significant increase in disparity occurred before maximum diversity. Archosaurs were rare components of Early–Middle Triassic faunas, but were more abundant in the Late Triassic and pre-eminent globally by the Early Jurassic. The archosaur radiation was a drawn-out event and major components such as diversity and abundance were discordant from each other. Crurotarsans (crocodile-line archosaurs) were more disparate, diverse, and abundant than avemetatarsalians (bird-line archosaurs, including dinosaurs) during the Late Triassic, but these roles were reversed in the Early Jurassic. There is no strong evidence that dinosaurs outcompeted or gradually eclipsed crurotarsans during the Late Triassic. Instead, crurotarsan diversity decreased precipitously by the end-Triassic extinction, which helped usher in the age of dinosaurian dominance.
An outbreak of waterborne cryptosporidiosis affecting 27 persons, diagnosed stool positive, occurred in Ayrshire in April 1988. Twenty-one of the 27 confirmed cases required some form of fluid replacement therapy. Local general practitioners indicated a two- to fivefold increase in diarrhoeal disease during the outbreak, and following enquiries made by Environmental Health Officers it became apparent that many hundreds of people had suffered a diarrhoeal illness at that time. Cryptosporidium spp. oocysts were detected in the treated chlorinated water supply system, in the absence of faecal bacterial indicators. Oocyst contamination of a break-pressure tank containing final water for distribution was the cause of this waterborne outbreak. An irregular seepage of oocyst-containing water, which increased during heavy rains, was the cause of the break-pressure tank contamination, rather than a failure of the water-treatment processes. The waterborne route should be considered when clusters of cryptosporidiosis associated with potable water occur. Waterborne cryptosporidiosis can occur in the absence of other faecal indicators of contamination.
The social stressors associated with the abrupt weaning process on commercial farms can result in significant welfare issues for pigs; including behavioural problems and aggression, decreased immunological responses, reduced live weight gain and efficiency of feed conversion (van de Weerd and Day, 2008). Slats and slurry systems in commercial housing systems for grower pigs provide a barren environment which may exacerbate these problems. Enriched environments have been shown to reduce aggression in pigs, particularly where devices that have manipulative and destructive properties are used (Scott et al, 2007). However, studies often include a single device that does not permit all animals to interact with the enrichment at any one time. The aim of the present study was to investigate the effects of multiple metal chain enrichment on levels of aggression in growing pigs.
Laryngopharyngeal reflux is perhaps the most extensively researched laryngology topic of the last decade. It has been suggested that some supraoesophageal symptoms, most notably asthma and laryngospasm, may be associated with night-time, or supine, reflux. The aim of this review was to assess the levels of evidence regarding a correlation between night-time reflux, snoring and apnoea.
A Medline search was performed using the terms ‘reflux’, ‘night-time’, ‘larynx’, ‘gastroesophageal’, ‘laryngopharyngeal’, ‘sleep’, ‘apnoea’, ‘snoring’ and ‘ear nose throat’. The retrieved literature was reviewed, focusing on randomised and non-randomised, controlled, prospective trials. Papers on both paediatric and adult populations were included. Non-English language papers were excluded.
We found no randomised, controlled trials or meta-analyses addressing the possible correlation between reflux and snoring and/or apnoea.
The role of night-time reflux in paediatric and adult snoring and apnoea is well described in the literature, but is based on poor levels of evidence from uncontrolled studies and case reports.
Young's syndrome describes a combination of male infertility, azoospermia, bronchiectasis and sinusitis. Although Young's syndrome is a well accepted disorder within the realms of infertility medicine, it is also accepted as being a potential cause of sino-nasal disease which is rarely seen by otolaryngologists. However, the significance of the sinus component within this triad is not fully understood. To gain further insight into the relationship of sinusitis with Young's syndrome, we reviewed all of the currently available published literature.
Within the reviewed literature, the diagnosis of sinusitis in Young's syndrome was crude and poorly defined; there was little emphasis on sinus disease in most publications.
The prevalence of Young's syndrome is reported to be declining, and the level of evidence regarding sinus disease within this syndrome is limited to case series only. There is, in fact, little evidence to support Young's syndrome being a significant aetiological factor for sinus disease, nor indeed to support the existence of Young's syndrome as an entity in its own right. The only documented aetiological factor is mercury exposure in childhood, an event that is seldom currently encountered; this would support our theory of the extinction of the condition. As an incidental finding, we found that the term Young's syndrome refers to two different medical conditions.
Fatty acid (FA) translocase (FAT)/CD36 is a key protein involved in regulating the uptake of FA across the plasma membrane in heart and skeletal muscle. A null mutation of FAT/CD36 reduces FA uptake rates and metabolism, while its overexpression increases FA uptake rates and metabolism. FA uptake into the myocyte may be regulated (a) by altering the expression of FAT/CD36, thereby increasing the plasmalemmal content of this protein (i.e. streptozotocin-induced diabetes, chronic muscle stimulation), or (b) by relocating this protein to the plasma membrane, without altering its expression (i.e. obese Zucker rats). By repressing FAT/CD36 expression, and thereby lowering the plasmalemmal FAT/CD36 (i.e. leptin-treated animals), the rate of FA transport is reduced. Within minutes of beginning muscle contraction or being exposed to insulin FA transport is increased. This increase is a result of the contraction- and insulin-induced translocation of FAT/CD36 from an intracellular depot to the cell surface. Neither PPARα nor PPARγ activation alter FAT/CD36 expression in muscle, despite the fact that PPARα activation increases FAT/CD36 by 80% in liver. A novel observation is that FAT/CD36 also appears to be involved in mitochondrial FA oxidation, as this protein is located on the mitochondrial membrane and seems to be required to participate in moving FA across the mitochondrial membrane. Clearly, FAT/CD36 has an important role in FA homeostasis in skeletal muscle and the heart.
Infantile bilateral striatal necrosis (IBSN) is characterized by a dystonic movement disorder and basal ganglia imaging abnormalities. Acute IBSN often occurs after upper respiratory tract infections although no specific micro-organism which may cause IBSN has been identified. We present 2 children (1 year 2 months and 4 years) with acute IBSN after clinical pharyngitis. Both IBSN patients had serological evidence of recent beta-haemolytic streptococcal infection. Due to the association of post-streptococcal disorders with anti-basal ganglia antibodies (ABGA), we examined both patients for anti-neuronal antibodies. For comparison, 20 children with dystonia (9 females, 11 males; mean age 4 years 1 month), and 20 children with uncomplicated streptococcal infection (12 females, 8 males; mean age 5 years 9 months) were examined. Both IBSN patients had antibodies reactive against basal ganglia constituents of molecular weight 40 kDa. Immunohistochemistry showed antibody reactivity against large striatal neurons only. Other anti-neuronal antibodies were negative, supporting striatal specificity. All controls were negative for ABGA. Acute IBSN is part of the post-streptococcal autoimmune neuropsychiatric spectrum. An autoimmune aetiology should be considered in this phenotype, as immunomodulatory therapies may reduce morbidity and mortality.
Moggi's computational lambda calculus is a metalanguage for
denotational semantics which
arose from the observation that many different notions of computation have
structure of a strong monad on a cartesian closed category. In this paper
we show that
the computational lambda calculus also arises naturally as the term calculus
(by the Curry–Howard correspondence) to a novel intuitionistic modal
We give natural deduction, sequent calculus and Hilbert-style presentations
of this logic and
prove strong normalisation and confluence results.
Metal contamination level will be decreased in order to maintain a device reliability according to device size reduction. Metal contamination from various processes are surveyed. The influence of metal contamination for 7–15nm thick gate oxides is discussed in order to clarify the critical concentration to gate oxides. NIG(Non Intrinsic Gettering) substrates are used in a worst case for gettering. Fe contamination with 4×1010 cm-2 strongly affects the TDDM characteristics, although there is no serious influence in the breakdown voltage even at the concentration of 5×1011 cm-2. The same tendency is observed for Cu contaminant and the critical concentration for TDDB characteristics is around 3×1011 cm-2. High energy B implantation is carried out to form gettering sites near device region. Breakdown voltage and TDDB characteristics are almost the same as epitaxial substrates at Fe concentration up to 1×1012 cm-2. Detailed examination such as SIMS, C-t and DLTS measurements is also supported the effectiveness in high energy gettering.