Children born prematurely: Cognitive outcomes and preliminary findings for subsequent intervention

Well-established evidence shows that children born preterm/low birth weight (LBW) are at increased risk of academic difficulties (Lee, Yeatman, Luna, & Feldman, 2011; Pritchard et al., 2009) and, despite global IQ scores within the normal range, nonetheless display lower academic performance than their same age peers (Bhutta, Cleves, Casey, Cradock, & Anand, 2002; Kerr-Wilson, Mackay, Smith, & Pell, 2011). This is not fully understood and previous attempts to improve these circumstances through means of cognitive intervention have met with little success. Therefore, the current thesis investigates possible underlying mechanisms of this intellectual disparity and tests the effectiveness of one potential intervention. In doing so, the studies presented focus specifically on fluid intelligence (Taub, 2002). The investigation through fluid intelligence is relatively novel in the current literature and therefore worthy of further exploration. Normal individual differences in fluid intelligence have been explained with reference to information processing parameters. Previous studies have shown that children born preterm/LBW have impairments in basic processes identified with executive function (Aarnoudse-Moens, Smidts, Oosterlaan, Duivenvoorden, & Weisglas-Kuperus, 2009; Mulder, Pitchford, Hagger, & Marlow, 2009). However, the current study is the first to test whether differences in fluid intelligence, as measured by the Cattell Culture Fair Tests, between preterm (n = 217) and typically developing children (n = 145) could be accounted for by differences in working memory and cognitive flexibility, as measured by the digit span tasks and the Wisconsin Card Sorting Test respectively. Results indicate that the seven to nine years old preterm cohort performed less well on measures of fluid intelligence than their peers across all age groups and their differences were partially mediated by both working memory and cognitive flexibility in a multiple mediation analysis. It also identified at least one year of developmental delay in fluid intelligence between the clinical group and their peers. Provided with evidence from Study 1 and parallel research suggesting that computerized working memory training may enhance working memory and fluid intelligence in non-clinical groups (Jaeggi, Buschkuehl, Jonides, & Perrig, 2008; Klingberg, Forssberg, & Westerberg, 2002; Studer et al., 2009), the second goal of this thesis was to conduct a preliminary study to investigate the feasibility of cognitive training for children born preterm/LBW. Therefore, in the second study, the utility of a brief adaptive working memory span training program (Buschkuehl, Jaeggi, Kobel, & Perrig, 2008) was tested in typically developing children. Sixty-three children, aged seven to nine years, were randomly assigned to one of three groups: Intervention, active control and passive control. The intervention group was trained in the adaptive version of the working memory span task and the active control group was trained in the nonadaptive version. Both groups trained for 15 minutes each day for a duration of 20 days. Participants in the passive control group participated only in pre and post assessments. All participants were assessed using the digit span and spatial span tasks for measuring working memory, the Stroop task for measuring executive control, a reaction time task for measuring processing speed and the Raven’s Standard Progressive Matrices for measuring fluid intelligence. Results indicate that children in the intervention group improved on their trained task and demonstrated significant far transfer effects on the assessment of fluid intelligence compared to both control groups. However, no near transfer to other measures was found. The reason behind the occurrence of far transfer effect without evidence of near transfer effects was unclear. However, given that the adaptive complex working memory training task was not in any way similar to the fluid intelligence measure, significant differences in fluid intelligence gains were unlikely to have been a consequence of practice or general familiarity effects but, rather, a consequence of the training. Although Study 1 identified that working memory and cognitive flexibility partially mediate birth status-related differences in Gf, the impact of these variables on academic performance in children born preterm is still unknown. Nonetheless, current evidence of far transfer to fluid intelligence after adaptive complex working memory span training provides support for the utility of WM training and modifiability in Gf. This in turn provides a preliminary evidence-base approach for psychologists to work toward providing neuro-remediation treatment options to targeted clinical groups, such as those born preterm with fluid intelligence deficiencies. In combination, the outcomes of these two studies provide both a theoretical contribution to our understanding of the deficits observed in children born preterm and an applied contribution to beginning the process of developing appropriate intervention programmes suitable for this clinical group in the future, with hopeful prospects for improving cognitive outcomes

Monitoring the Effects of Anti-angiogenesis on the Radiation Sensitivity of Pancreatic Cancer Xenografts Using Dynamic Contrast-Enhanced CT

Purpose To image the intra-tumor vascular physiological status of pancreatic tumors xenografts and their response to anti-angiogenic therapy using Dynamic Contrast-Enhanced CT (DCE-CT), and to identify parameters of vascular physiology associated with tumor X-ray sensitivity following anti-angiogenic therapy. Methods and Materials Nude mice bearing human BxPC-3 pancreatic tumor xenografts were treated with 5Gy of radiation therapy (RT), either a low-dose (40mg/kg) or a high-dose (150mg/kg) of DC101, the anti-VEGF receptor-2 anti-angiogenesis antibody, or with combination of low or high dose DC101 and 5Gy RT (DC101-plus-RT). DCE-CT scans were longitudinally acquired over three week period post-DC101 treatment. Parametric maps of tumor perfusion and fractional plasma volume (Fp) were calculated and their averaged values and histogram distributions evaluated and compared to controls, from which a more homogeneous physiological window was observed 1-week post-DC101. Mice receiving a combination of DC101-plus-RT(5Gy) were imaged baseline prior to receiving DC101 and 1-week after DC101 (prior to RT). Changes in perfusion and Fp were compared with alternation in tumor growth delay for RT and DC101-plus-RT(5Gy) treated tumors. Results Pretreatment with low or high doses of DC101 prior to RT significantly delayed tumor growth by an average 7.9 days compared to RT alone (p≤0.01). The increase in tumor growth delay for the DC101-plus-RT treated tumors was strongly associated with changes in tumor perfusion (ΔP>−15%) compared to RT treated tumors alone (p=0.01). In addition, further analysis revealed a trend linking the tumor’s increased growth delay to its tumor volume-to-DC101 dose ratio. Conclusions DCE-CT is capable of monitoring changes in intra-tumor physiological parameter of tumor perfusion in response to anti-angiogenic therapy of a pancreatic human tumor xenograft that was associated with enhanced radiation response

Adverse drug reactions in Ghanaian children: review of reports from 2000 to 2012 in VigiBase

Objective: The aim of this article is to describe adverse drug reactions (ADRs) reported for children aged 0 - 17 years in Ghana. Methods: Paediatric reports submitted by the Ghana National Centre for Pharmacovigilance to the World Health Organisation (WHO) Global ADR database, VigiBase up to December 2012 were extracted. The data were analysed for number of reports per year, types of reporters and suspected ADRs and drugs. Results: A total of 343 reports for children were received during the period. The drug classes most frequently reported were vaccines (115, 31%), antimalarials (106, 28%) and antibiotics (57, 15%). Of the top 20 individual drugs, 19 were anti-infectives. The most frequently reported ADRs were injection site infection, fever and rash. There were 23 deaths reported, and antimalarials were implicated in 12 cases. Conclusions: Vaccines, antimalarials and antibiotics are the leading medicines reported to cause ADRs in Ghanaian children. There was a high mortality rate, with many of the deaths due to causes explained in the individual case safety reports

Louis C. Wyman to John D. Feerick

Letter from Representative Louis C. Wyman to Dean John D. Feerick, regarding his scholarly article on presidential inability.https://ir.lawnet.fordham.edu/twentyfifth_amendment_correspondence/1017/thumbnail.jp

A systematic review of the evidence for single stage and two stage revision of infected knee replacement

BACKGROUND: Periprosthetic infection about the knee is a devastating complication that may affect between 1% and 5% of knee replacement. With over 79 000 knee replacements being implanted each year in the UK, periprosthetic infection (PJI) is set to become an important burden of disease and cost to the healthcare economy. One of the important controversies in treatment of PJI is whether a single stage revision operation is superior to a two-stage procedure. This study sought to systematically evaluate the published evidence to determine which technique had lowest reinfection rates. METHODS: A systematic review of the literature was undertaken using the MEDLINE and EMBASE databases with the aim to identify existing studies that present the outcomes of each surgical technique. Reinfection rate was the primary outcome measure. Studies of specific subsets of patients such as resistant organisms were excluded. RESULTS: 63 studies were identified that met the inclusion criteria. The majority of which (58) were reports of two-stage revision. Reinfection rated varied between 0% and 41% in two-stage studies, and 0% and 11% in single stage studies. No clinical trials were identified and the majority of studies were observational studies. CONCLUSIONS: Evidence for both one-stage and two-stage revision is largely of low quality. The evidence basis for two-stage revision is significantly larger, and further work into direct comparison between the two techniques should be undertaken as a priority

Ischemic Colitis of the Left Colon in a Diabetic Patient

Diabetes mellitus may affect the gastrointestinal tract possibly as a result of autonomic neuropathy. Here we present a 68-year-old male with non-insulin-dependent diabetes mellitus who presented with prolonged watery diarrhea and in whom imaging studies demonstrated ischemic colitis of the left colon. Resection of the affected colon resulted in sustained disappearance of symptoms

Association between intimate partner violence and leukocyte telomere length: a retrospective cohort study of 144 049 UK Biobank participants

Abstract Aims Intimate partner violence (IPV) is a public health challenge negatively affecting victims’ health. Telomere length (TL), a marker for biological ageing, might be reflective of the mechanisms through which IPV leads to adverse health outcomes. The objective of the current study was to explore the association between IPV and leucocyte TL. Methods We conducted an analysis using a subset of the UK Biobank (N = 144 049). Physical, sexual and emotional IPV were reported by the participants. DNA was extracted from peripheral blood leukocytes. TL was assayed by quantitative polymerase chain reaction. We used multivariable linear regressions to test the associations between IPV and TL adjusted for age, sex, ethnicity, deprivation, education, as well as symptoms of depression and post-traumatic stress disorder in a sensitivity analysis. Results After adjusting for sociodemographic factors, any IPV was associated with 0.02-s.d. shorter TL (β = −0.02, 95% CI −0.04 to −0.01). Of the three types of IPV, physical violence had a marginally stronger association (β = −0.05, 95% CI −0.07 to −0.02) than the other two types. The associations of numbers of IPV and TL showed a dose–response pattern whereby those who experienced all three types of IPV types had the shortest TL (β = −0.07, 95% CI −0.12 to −0.03), followed by those who experienced two types (β = −0.04, 95% CI −0.07 to −0.01). Following additional adjustment for symptoms of depression and PTSD, the associations were slightly attenuated but the general trend by number of IPVs remained. Conclusions Victims of IPV, particularly those exposed to multiple types of IPVs, had shorter TL indicative of accelerated biological ageing. Given that all three types of IPV are linked to TL, clinical practitioners need to comprehensively identify all types of IPV and those who received multiple types. Further studies should explore the association of violence with changes in TL over time, as well as to which extent biological ageing is a mechanistic factor

The impact of unhealthy food sponsorship vs. pro-health sponsorship models on young adults' food preferences: A randomised controlled trial

Background: Unhealthy foods are promoted heavily, through food company sponsorship of elite sport, resulting in extensive exposure among young adults who are avid sport spectators. This study explores the effects of sponsorship of an elite sporting event by: (A) non-food brands (control), (B) unhealthy food brands, (C) healthier food brands, or (D) an obesity prevention public health campaign on young adults' brand awareness, attitudes, image perceptions, event-sponsor fit perceptions, and preference for food sponsors' products. Methods: A between-subjects web-based experiment was conducted, consisting of four sponsorship conditions (A through D) featuring three product categories within each condition. Australian adults (N = 1132) aged 18-24 years were recruited via a national online panel. Participants viewed promotional videos and news stories about an upcoming international, multi-sport event (with sponsor content edited to reflect each condition), completed a distractor task, and then answered questions assessing the response variables. Regression analyses were conducted to test for differences by sponsorship condition on the respective outcome measures. Results: Compared to the control condition, unhealthy food sponsorship promoted higher awareness of, and more favourable attitudes towards, unhealthy food sponsor brands. Unhealthy food sponsorship also led to greater perceived event-sponsor fit and transfer of perceptions of the sporting event to the unhealthy food sponsor brands, relative to the control group. Exposure to sponsorship for healthier foods produced similar sponsorship effects for healthier food sponsor brands, as well as prompting a significant increase in the proportion of young adults showing a preference for these products. Obesity prevention campaign sponsorship promoted higher campaign awareness and perceived event-sponsor fit, but did not impact food attitudes or preference for unhealthy versus healthier foods. Conclusion: Findings suggest that restricting elite sport sponsorship to healthier food brands that meet set nutritional criteria could help promote healthier eating among young adults. Sporting organisations should be encouraged to seek sponsorship from companies who produce healthier food brands and government-funded social marketing campaigns. Clinical trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) registration number ACTRN12618000368235. Retrospectively registered 12 March 2018

Hepatocytic expression of human sodium-taurocholate cotransporting polypeptide enables hepatitis B virus infection of macaques

Hepatitis B virus (HBV) is a major global health concern, and the development of curative therapeutics is urgently needed. Such efforts are impeded by the lack of a physiologically relevant, pre-clinical animal model of HBV infection. Here, we report that expression of the HBV entry receptor, human sodium-taurocholate cotransporting polypeptide (hNTCP), on macaque primary hepatocytes facilitates HBV infection in vitro, where all replicative intermediates including covalently closed circular DNA (cccDNA) are present. Furthermore, viral vector-mediated expression of hNTCP on hepatocytes in vivo renders rhesus macaques permissive to HBV infection. These in vivo macaque HBV infections are characterized by longitudinal HBV DNA in serum, and detection of HBV DNA, RNA, and HBV core antigen (HBcAg) in hepatocytes. Together, these results show that expressing hNTCP on macaque hepatocytes renders them susceptible to HBV infection, thereby establishing a physiologically relevant model of HBV infection to study immune clearance and test therapeutic and curative approaches