Early childhood neurodevelopment after intrauterine growth restriction: a systematic review

BACKGROUND AND OBJECTIVE: Children who experienced intrauterine growth restriction (IUGR) may be at increased risk for adverse developmental outcomes in early childhood. The objective of this study was to carry out a systematic review of neurodevelopmental outcomes from 6 months to 3 years after IUGR.

METHODS: PubMed, Embase, PsycINFO, Maternity and Infant Care, and CINAHL databases were searched by using the search terms intrauterine, fetal, growth restriction, child development, neurodevelopment, early childhood, cognitive, motor, speech, language. Studies were eligible for inclusion if participants met specified criteria for growth restriction, follow-up was conducted within 6 months to 3 years, methods were adequately described, non-IUGR comparison groups were included, and full English text of the article was available. A specifically designed data extraction form was used. The methodological quality of included studies was assessed using well-documented quality-appraisal guidelines.

RESULTS: Of 731 studies reviewed, 16 were included. Poorer neurodevelopmental outcomes after IUGR were described in 11. Ten found motor, 8 cognitive, and 7 language delays. Other delays included social development, attention, and adaptive behavior. Only 8 included abnormal Doppler parameters in their definitions of IUGR.

CONCLUSIONS: Evidence suggests that children are at risk for poorer neurodevelopmental outcomes following IUGR from 6 months to 3 years of age. The heterogeneity of primary outcomes, assessment measures, adjustment for confounding variables, and definitions of IUGR limits synthesis and interpretation. Sample sizes in most studies were small, and some examined preterm IUGR children without including term IUGR or AGA comparison groups, limiting the value of extant studies.

The Day After Tomorrow: Transition Management, Spatial Planning & the Low Carbon Economy

Many of the societal challenges that current spatial planning practice claims to be addressing (climate change, peak oil, obesity, aging society etc) encompass issues and timescales that lie beyond the traditional scope planning policy (Campbell 2006). The example of achieving a low carbon economy typifies this in that it demands a process of society-wide transition, involving steering a wide range of factors (markets, infrastructure, governance, individual behaviour etc). Such a process offers a challenge to traditional approaches to planning as they cannot be guided by a fixed blueprint, given the timescales involved (up to 50 years) and an enhanced level of uncertainty, social resistance, lack of control over implementation and a danger of ‘policy lock in’ (Kemp et al 2007). One approach to responding to these challenges is the concept of transition management which has emerged from studies of science, technology and innovation (Geels 2002, Markard et al 2012). Although not without criticism, this perspective attempts to uncertainty and complexity encompassing long term visions that integrates multi-level, multi-actor and multi-domain perspectives (Rotmans et al 2001).
 
Given its origins, research on transition management has tended to neglect spatial contexts (Coenen et al 2012) and, related to this, it’s relationship with spatial planning is poorly understood. Using the example of the low carbon transition, this paper will review the relationships between the concepts, methodologies and goals of transition management and spatial planning to explore whether a closer integration of the two fields offers benefits to achieving the long term challenges facing society.
 

Investigation of organic xenobiotic transfers, partitioning and processing in air-soil-plant systems using a microcosm apparatus. Part I:Microcosm development

A microcosm system was developed to investigate transfers of organic xenobiotics in air-soil-plant systems. This was validated using ¹⁴C labelled 1,2-dichlorobenzene (DCB) as a model compound. Trapping efficiency was 106 ± 3% for volatile compounds and 93.0 ± 2.2% for carbon dioxide in a blank microcosm arrangement. Recovery of 1,2-dichlorobenzene spiked to grassed and unplanted soils was > 90% after 1 week. The predominant DCB loss process was volatilisation with no evidence for mineralisation over 1 week and 20-30% of the added spike remained in soil. Although there was no evidence for root uptake and translocation of added label, foliar uptake of soil volatilised compound was detected. The microcosm showed good potential for study of ¹⁴C labelled and unlabelled organic xenobiotic transfers in air-soil-plant systems with single plants and also intact planted cores.

Marrow aplasia developing 13 years after HLA-identical sibling allogeneic transplantation for chronic myeloid leukaemia:successful treatment with antithymocyte globulin and peripheral blood stem cell infusion from the original donor

Secondary or late graft failure has been defined as the development of inadequate marrow function after initial engraftment has been achieved. We describe a case of profound marrow aplasia occurring 13 years after sibling allogeneic bone marrow transplantation for chronic myeloid leukaemia (CML) in first chronic phase. Although the patient remained a complete donor chimera, thereby suggesting that an unselected infusion of donor peripheral blood stem cells (PBSC) or bone marrow might be indicated, the newly acquired aplasia was thought to be immune in aetiology and some immunosuppression was therefore considered appropriate. Rapid haematological recovery was achieved after the infusion of unselected PBSC from the original donor following conditioning with anti-thymocyte globulin (ATG).

Plastin Polymorphisms Predict Gender- and Stage-Specific Colon Cancer Recurrence after Adjuvant Chemotherapy

Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes PLS3 and LCP1 are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32-6.1; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09-3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets.

A pilot study to develop an assessment tool for sheep welfare after long journey transport

Sheep transport within Europe involves 9.5 million animals yearly, 63% of which travel over longjourneys (> 8 h). Livestock transport, particularly over long journeys, gives rise to concern about the welfare of transported animals. The European Commission stimulates the development of market-oriented animal welfare standards for all phases of livestock production, providing an alternative to the 'regulatory approach'. This study aimed to develop and test a new sheep welfare assessment protocol to be used following transport, irrespective of the journey purpose. The protocol included outcome (animal-based measures) and input variables (resource-based and management-based measures), being welfare-relevant aspects of both transport and unloading procedures. Weighted Cohen's Kappa and Heiss' Kappa index of agreement were calculated to evaluate the raters accuracy and the inter-observer reliability.Overall, good agreement levels were found. The protocol was tested on 40 commercial transports arriving at previously selected assembly centres and slaughterhouses in Italy and Greece. The protocol was found to be feasible when applied to commercial transports, allowing for a comprehensive and quick sheep welfare assessment during unloading, without impairing stockman work. Univariate analysis was carried out to evaluate associations between outcome and input variables. In this study, significant association between outcome measures and risk factors were identified when associated to unloading procedures but not to travel conditions. In collaboration with the relevant stakeholders, this protocol might be developed into a tool for routine checks for certification purposes and could provide direct feedback to all professionals involved in animal transportation on the weaknesses and strengths of their work.

The effect of pantethine and ultraviolet-B radiation on the development of lenticular opacity in the emory mouse.

PURPOSE: Few studies have examined the impact of long-term treatments or exposures on the development of cataract in maturity-onset animal models. We studied the effect of treatment with D-pantethine and exposure to ultraviolet-B (UVB) radiation on the development of lenticular opacity in the Emory mouse. METHODS: A total of 164 Emory mice were randomized by litter at weaning to exposure to UVB light at 12 mJ/cm(2) for 6 hr/day (UV) or usual room light (A), and within litter, were further randomized to bi-weekly intra-peritoneal injections of 0.8 g/kg pantethine (T) or no treatment (C). Retro illumination lens photos were taken at 2, 4, 6, 8, and 10 months after weaning, and graded in masked fashion. The animals were sacrificed at 10 months and the lenses analyzed for total pantethine and total cysteamine. RESULTS: Lens pantethine and cysteamine levels were significantly (P < 0.001) higher for the T as compared to C litters. Mean cataract grade increased monotonically over time for all four groups. Unadjusted mean grade for the AT group at 8 (1.32) and 10 (1.86) months appeared lower than for the other groups (AC: 2.17, 2.39; UVC: 1.77, 2.40; UVT: 1.88, 2.37). However, the mean grade for the pantethine-treated litters did not differ significantly from the untreated litters except at 2 months (when untreated litters had significantly lower grades), when adjusting for UV treatment, gender and litter effect. No significant difference in cataract score existed between UV-exposed and ambient litters. Mortality was higher among pantethine-treated (hazard ratio = 1.8, p = 0.05) and UV-exposed animals (hazard ratio = 1.8, p = 0. 03) than among the untreated and unexposed litters. CONCLUSION: Significantly increased lens levels of pantethine are achieved with long-term intra-peritoneal dosing. The impact of pantethine on the progression of lenticular opacity in the Emory mouse is less than has been reported in other models. This level of chronic UVB exposure appeared to have no effect on the development of cataract in this model.

Cataract after glaucoma filtration surgery.

PURPOSE:

We reviewed the evidence regarding cataract incidence and progression after glaucoma surgery.

DESIGN:

Evidence-based review of available literature.

METHODS:

We performed a systematic review of relevant studies published in English.

RESULTS:

Reports of visually significant cataract after glaucoma surgery are supported by data from randomized clinical trials and large case series.

CONCLUSIONS:

Patients undergoing glaucoma surgery are at increased risk for the development and progression of cataract.

Nuclear cataract shows significant familial aggregation in an older population after adjustment for possible shared environmental factors.

PURPOSE: To quantify the association between siblings in age-related nuclear cataract, after adjusting for known environmental and personal risk factors. METHODS: All participants (probands) in the Salisbury Eye Evaluation (SEE) project and their locally resident siblings underwent digital slit lamp photography and were administered a questionnaire to assess risk factors for cataract including: age, gender, lifetime sun exposure, smoking and diabetes history, and use of alcohol and medications such as estrogens and steroids. In addition, blood pressure, body mass index, and serum antioxidants were measured in all participants. Lens photographs were graded by trained observers masked to the subjects' identity, using the Wilmer Cataract Grading System. The odds ratio for siblings for affectedness with nuclear cataract and the sibling correlation of nuclear cataract grade, after adjusting for covariates, were estimated with generalized estimating equations. RESULTS: Among 307 probands (mean age, 77.6 +/- 4.5 years) and 434 full siblings (mean age, 72.4 +/- 7.4 years), the average sibship size was 2.7 per family. After adjustment for covariates, the probability of development of nuclear cataract was significantly increased (odds ratio [OR] = 2.07, 95% confidence interval [CI], 1.30-3.30) among individuals with a sibling with nuclear cataract (nuclear grade > or = 3.0). The final fitted model indicated a magnitude of heritability for nuclear cataract of 35.6% (95% CI: 21.0%-50.3%) after adjustment for the covariates. CONCLUSIONS: Findings in this study are consistent with a genetic effect for age-related nuclear cataract, a common and clinically significant form of lens opacity.

The Development of Regret and Relief About the Outcomes of Risky Decisions

Although a number of studies have examined the developmental emergence of counterfactual emotions of regret and relief, none of these have used tasks that resemble those used with adolescents and adults, which typically involve risky decision making. We examined the development of the counterfactual emotions of regret and relief in two experiments using a task in which children chose between one of two gambles that varied in risk. In regret trials they always received the best prize from that gamble but were then shown that they would have obtained a better prize had they chosen the alternative gamble, whereas in relief trials the other prize was worse. We compared two methods of measuring regret and relief based on children’s reported emotion on discovering the outcome of the alternative gamble, one in which children judged whether they now felt the same, happier, or sadder on seeing the other prize and one in which children made emotion ratings on a 7-point scale after the other prize was revealed. On both these methods, we found that 6- to 7-year-olds’ and 8- to 9-year-olds’ emotions varied appropriately depending on whether the alternative outcome was better or worse than the prize they had actually obtained, although the former method was more sensitive. Our findings indicate that by at least 6-7 years, children experience the same sorts of counterfactual emotions as adults in risky decision making tasks, and also suggest that such emotions are best measured by asking children to make comparative emotion judgments.

The Importance of DNA methylation in Prostate Cancer development

After briefly reviewing the nature of DNA methylation, its general role in cancer and the tools available to interrogate it, we consider the literature surrounding DNA methylation as relating to prostate cancer. Specific consideration is given to recurrent alterations. A list of frequently reported genes is synthesised from seventeen studies that have reported on methylation changes in malignant prostate tissue, and we chart the timing of those changes in the diseases history through amalgamation of several previously published data sets. We also review associations with genetic alterations and hormone signalling, before the practicalities of investigating prostate cancer methylation using cell lines are assessed. We conclude by outlining the interplay between DNA methylation and prostate cancer metabolism and their regulation by Androgen Receptor, with a specific discussion of the mitochondria and their associations with DNA methylation.

Development of the Consumer Refrigerator Safety Questionnaire (CRSQ): A Measure of Consumer Perceptions and Practices

Food preparation and storage behaviors in the home deviating from the ‘best practice’ food safety recommendations may result in food borne illnesses. Currently, there are limited tools available to fully evaluate the consumer knowledge, perceptions and behavior in the area of refrigerator safety. The current study aimed to develop a valid and reliable tool in the form of a questionnaire (CFSQCRSQ) for assessing systematically all these aspects. Items relating to refrigerator safety knowledge (n=17), perceptions (n=46), reported behavior (n=30) were developed and pilot tested by an expert reference group and various consumer groups to assess face and content validity (n=20), item difficulty and item consistency (n=55) and construct validity (n=23). The findings showed that the CFSQCRSQ has acceptable face and content validity with acceptable levels of item difficulty. Item consistency was observed for 12 out of 15 refrigerator safety knowledge. Further, all five of the subscales of consumer perceptions of refrigerator safety practices relating to risk of developing foodborne disease food poisoning showed acceptable internal consistency (Cronbach’s α value > 0.8). Construct validity of the CFSQCRSQ was shown to be very good (p=0.022). The CFSQCRSQ exhibited acceptable test-retest reliability at 14 days with majority of knowledge items (93.3%) and reported behavior items (96.4%) having correlation coefficients of greater than 0.70. Overall, the CFSQCRSQ was deemed valid and reliable in assessing refrigerator safety knowledge and behavior and therefore has the potential for future use in identifying groups of individuals at increased risk of deviating from recommended refrigerator safety practices as well as the assessment of refrigerator safety knowledge, behavior for use before and after an intervention.