Changes in invertebrate assemblage composition in benthic and hyporheic zones during a severe supraseasonal drought

Droughts are unpredictable disturbances characterized in streams by declining flow, reduced habitat availability, and deteriorating abiotic conditions. Such events typically reduce benthic invertebrate taxon richness and modify assemblage composition, but little is known about how hyporheic invertebrate assemblages respond to drought or how these responses relate to changes in benthic assemblages. We hypothesized that taxon richness (diversity) and variability (as within-site diversity) in benthic assemblage composition would decline as drought proceeded, whereas concurrent changes in hyporheic assemblages would be lower in this more stable environment. We predicted that benthic assemblage composition between sites would converge as epigean taxa were selectively eliminated, whereas between-site hyporheic diversity would change little. We sampled benthic and hyporheic invertebrates concurrently from 4 sites along a groundwater-fed stream during the final stages of a severe supraseasonal drought punctuated by a record heat wave. Abiotic conditions in benthic habitats deteriorated as flow declined, but changes were less pronounced in the hyporheic zone. Benthic diversity declined during drought, whereas hyporheic diversity changed little. However, benthic within-site diversity increased as the drought progressed because of localized variation in the abundance of common taxa. Temporal trends in hyporheic diversity were less consistent. Benthic assemblages at individual sites became more similar, especially during the heat wave, reflecting low diversity and abundance. Hyporheic assemblages changed markedly because of temporary increases in abundances of epigean and hypogean amphipods. These contrasting responses of benthic and hyporheic assemblages to drought should be recognized when developing management strategies for drought-impacted streams

Investigating the missing data mechanism in quality of life outcomes: a comparison of approaches

Background: Missing data is classified as missing completely at random (MCAR), missing at random (MAR) or missing not at random (MNAR). Knowing the mechanism is useful in identifying the most appropriate analysis. The first aim was to compare different methods for identifying this missing data mechanism to determine if they gave consistent conclusions. Secondly, to investigate whether the reminder-response data can be utilised to help identify the missing data mechanism. Methods: Five clinical trial datasets that employed a reminder system at follow-up were used. Some quality of life questionnaires were initially missing, but later recovered through reminders. Four methods of determining the missing data mechanism were applied. Two response data scenarios were considered. Firstly, immediate data only; secondly, all observed responses (including reminder-response). Results: In three of five trials the hypothesis tests found evidence against the MCAR assumption. Logistic regression suggested MAR, but was able to use the reminder-collected data to highlight potential MNAR data in two trials. Conclusion: The four methods were consistent in determining the missingness mechanism. One hypothesis test was preferred as it is applicable with intermittent missingness. Some inconsistencies between the two data scenarios were found. Ignoring the reminder data could potentially give a distorted view of the missingness mechanism. Utilising reminder data allowed the possibility of MNAR to be considered.The Chief Scientist Office of the Scottish Government Health Directorate. Research Training Fellowship (CZF/1/31

Underexpression of the 43 kDa inositol polyphosphate 5-phosphatase is associated with spontaneous calcium oscillations and enhanced calcium responses following endothelin-1 stimulation

The 43 kDa inositol polyphosphate 5-phosphatase (5-phosphatase) hydrolyses the signalling molecules inositol 1,4,5-trisphosphate (Ins(1,4,5)P) and inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P) and thereby regulates cellular transformation. To investigate the role Ins(1,4,5)P-mediated Ca oscillations play in cellular transformation, we studied Ins(1,4,5)P-mediated Ca responses in cells underexpressing the 43 kDa 5-phosphatase. Chronic reduction in 43 kDa 5-phosphatase enzyme activity resulted in a 2.6-fold increase in the resting Ins(1,4,5)P concentration and a 4.1-fold increase in basal intracellular Ca. The increased Ins(1,4,5)P levels resulted in partial emptying (40%) of the Ins(1,4,5)P-sensitive Ca store, however, store-operated Ca influx remained unchanged. In addition, Ins(1,4,5)P receptors were chronically downregulated in unstimulated cells, as shown by a 53% reduction in [H]Ins(1,4,5)P binding to microsomal receptor sites. Agonist stimulation with endothelin-1 resulted in the rapid rise and fall of Ins(1,4,5)P and Ins(1,3,4,5)P levels, with no significant differences in the rates of hydrolysis of these second messengers in antisenseor vector-transfected cells. These studies indicate, in contrast to its predicted action, the 43 kDa 5-phosphatase does not metabolise Ins(1,4,5)P and Ins(1,3,4,5)P post agonist stimulation. Cells with decreased 43 kDa 5-phosphatase activity exhibited spontaneous Ca oscillations in the absence of any agonist stimulation, and increased sensitivity and amplitude of intracellular Ca responses to both high and low dose endothelin-l stimulation. We conclude the 43 kDa 5-phosphatase exerts a profound influence on Ins(1,4,5)P-induced Ca spiking, both in the unstimulated cell and following agonist stimulation. We propose the enhanced Ca oscillations may mediate cellular transformation in cells underexpressing the 43 kDa 5-phosphatase

Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility

Susceptible periods during embryogenesis of the heart and endocrine glands.

One of the original principles of teratology states that, "Susceptibility to teratogenesis varies with the developmental stage at the time of exposure to an adverse influence" [Wilson JG. Environment and Birth Defects. New York:Academic Press, 1973]. The time of greatest sensitivity encompasses the period of organ formation during weeks 3-8 following fertilization in human gestation. At this time, stem cell populations for each organ's morphogenesis are established and inductive events for the initiation of differentiation occur. Structural defects of the heart and endocrine system are no exception to this axiom and have their origins during this time frame. Although the function and maturation of these organs may be affected at later stages, structural defects and loss of cell types usually occur during these early phases of development. Thus, to determine critical windows for studying mechanisms of teratogenesis, it is essential to understand the developmental processes that establish these organs

What gives rise to clinician gut feeling, its influence on management decisions and its prognostic value for children with RTI in primary care: a prospective cohort study.

BACKGROUND: The objectives were to identify 1) the clinician and child characteristics associated with; 2) clinical management decisions following from, and; 3) the prognostic value of; a clinician's 'gut feeling something is wrong' for children presenting to primary care with acute cough and respiratory tract infection (RTI). METHODS: Multicentre prospective cohort study where 518 primary care clinicians across 244 general practices in England assessed 8394 children aged ≥3 months and < 16 years for acute cough and RTI. The main outcome measures were: Self-reported clinician 'gut feeling'; clinician management decisions (antibiotic prescribing, referral for acute admission); and child's prognosis (reconsultation with evidence of illness deterioration, hospital admission in the 30 days following recruitment). RESULTS: Clinician years since qualification, parent reported symptoms (illness severity score ≥ 7/10, severe fever < 24 h, low energy, shortness of breath) and clinical examination findings (crackles/ crepitations on chest auscultation, recession, pallor, bronchial breathing, wheeze, temperature ≥ 37.8 °C, tachypnoea and inflamed pharynx) independently contributed towards a clinician 'gut feeling that something was wrong'. 'Gut feeling' was independently associated with increased antibiotic prescribing and referral for secondary care assessment. After adjustment for other associated factors, gut feeling was not associated with reconsultations or hospital admissions. CONCLUSIONS: Clinicians were more likely to report a gut feeling something is wrong, when they were more experienced or when children were more unwell. Gut feeling is independently and strongly associated with antibiotic prescribing and referral to secondary care, but not with two indicators of poor child health

Ecological effects of a supra-seasonal drought on macroinvertebrate communities differ between near-perennial and ephemeral river reaches

The duration, intensity and frequency of hydrological droughts are predicted to increase significantly over the 21st century globally, threatening the long-term stability of lotic communities. In this paper we examine the recovery and recolonization of macroinvertebrate taxa in ephemeral and near perennial reaches of the River Lathkill (UK) after a supra-seasonal drought event. Following flow resumption, species accumulation (recolonization) occurred rapidly over a 4-month period, with a steady increase observed thereafter. Taxonomic richness was significantly higher in the section with near perennial flow after the first month of the study than the naturally ephemeral reach. Serial correlation was observed in the near perennial section but not in the upstream ephemeral reach. Serial correlation in the near perennial section may reflect: (1) the ongoing process of recovery or (2) the macroinvertebrate community following a new ecological trajectory. Our results suggest that supra-seasonal droughts may cause initial reductions in lotic diversity during stream desiccation events but may re-set ecological succession and/or temporarily provide new ecological niches, thereby supporting increased taxonomic diversity when the full range of hydrological conditions are considered. Quantifying the recovery of ecological communities following supra-seasonal drought can provide information to help develop ecologically effective conservation and management strategies

Simple models of the chemical field around swimming plankton

Background. Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk. Methods. Here, we used HLA and KIR dosages imputed from single-nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and 13 858 healthy controls of European decent. Results. The following 4 novel HLA alleles were identified in association with cervical neoplasia, owing to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles: HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 × 10−9), HLA-DRB5*0101 (OR, 1.29; P = 2.26 × 10−8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 × 10−9), and HLA-DRB3*0301 (OR, 0.63; P = 4.06 × 10−5). We also found that homozygosity of HLA-C1 group alleles is a protective factor for human papillomavirus type 16 (HPV16)-related cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR, 0.69; P = .0006). Conclusions. Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism

Multiple Imputation Ensembles (MIE) for dealing with missing data

Missing data is a significant issue in many real-world datasets, yet there are no robust methods for dealing with it appropriately. In this paper, we propose a robust approach to dealing with missing data in classification problems: Multiple Imputation Ensembles (MIE). Our method integrates two approaches: multiple imputation and ensemble methods and compares two types of ensembles: bagging and stacking. We also propose a robust experimental set-up using 20 benchmark datasets from the UCI machine learning repository. For each dataset, we introduce increasing amounts of data Missing Completely at Random. Firstly, we use a number of single/multiple imputation methods to recover the missing values and then ensemble a number of different classifiers built on the imputed data. We assess the quality of the imputation by using dissimilarity measures. We also evaluate the MIE performance by comparing classification accuracy on the complete and imputed data. Furthermore, we use the accuracy of simple imputation as a benchmark for comparison. We find that our proposed approach combining multiple imputation with ensemble techniques outperform others, particularly as missing data increases

Low temperature scattering with the R-matrix method: the Morse potential

Experiments are starting to probe collisions and chemical reactions between atoms and molecules at ultra-low temperatures. We have developed a new theoretical procedure for studying these collisions using the R-matrix method. Here this method is tested for the atom -- atom collisions described by a Morse potential. Analytic solutions for continuum states of the Morse potential are derived and compared with numerical results computed using an R-matrix method where the inner region wavefunctions are obtained using a standard nuclear motion algorithm. Results are given for eigenphases and scattering lengths. Excellent agreement is obtained in all cases. Progress in developing a general procedure for treating ultra-low energy reactive and non-reactive collisions is discussed.Comment: 18 pages, 6 figures, 3 tables, conferenc