The impact of maternal inflammation and maternal stress in the regulation of neurodevelopment and physiological function

The mechanisms governing fetal development follow a tightly regulated pattern of progression such that interference at any one particular stage is likely to have consequences for all other stages of development in the physiological system that has been affected thereafter. These disturbances can take the form of many different events but two of the most common and widely implicated in causing detrimental effects to the developing fetus are maternal immune activation (MIA) and maternal stress. MIA has been shown to cause an increase in circulating proinflammatory cytokines in both the maternal and fetal circulation. This increase in proinflammatory mediators in the fetus is thought to occur by fetal production rather than through exchange between the maternal-fetal interface. In the case of maternal stress it is increased levels of stress related hormones such as cortisol/corticosterone which is thought to elicit the detrimental effects on fetal development. In the case of both maternal infection and stress the timing and nature of the insult generally dictates the severity and type of effects seen in affected offspring. We investigated the effect of a proinflammatory environment on neural precursor cells of which exposure resulted in a significant decrease in the normal rate of proliferation of NPCs in culture but did not have any effect on cell survival. These effects were seen to be age dependent. Using a restraint stress model we investigated the effects of prenatal stress on the development of a number of different physiological systems in the same cohort of animals. PNS animals exhibited a number of aberrant changes in cardiovascular function with altered responses to stress and hypertension, modifications in respiratory responses to hypercapnic and hypoxic challenges and discrepancies in gastrointestinal innervation. Taken together these findings suggest that both maternal infection and maternal stress are detrimental to the normal development of the fetus.

Investigative Interviewing and Memory: How Accurate Are Interviewers’ Recollections of Investigative Interviews?

Contrary to interviewing guidelines, a considerable portion of witness interviews are not recorded. Investigators’ memory, their interview notes, and any subsequent interview reports therefore become important pieces of evidence; the accuracy of interviewers’ memory or such reports is therefore of crucial importance when interviewers testify in court regarding witness interviews. A detailed recollection of the actual exchange during such interviews and how information was elicited from the witness will allow for a better assessment of statement veracity in court. Two studies were designed to examine interviewers’ memory for a prior witness interview. Study One varied interviewer note-taking and type of subsequent interview report written by interviewers by including a sample of undergraduates and implementing a two-week delay between interview and recall. Study Two varied levels of interviewing experience in addition to report type and note-taking by comparing experienced police interviewers to a student sample. Participants interviewed a mock witness about a crime, while taking notes or not, and wrote an interview report two weeks later (Study One) or immediately after (Study Two). Interview reports were written either in a summarized format, which asked interviewers for a summary of everything that occurred during the interview, or verbatim format, which asked interviewers to record in transcript format the questions they asked and the witness’s responses. Interviews were videotaped and transcribed. Transcriptions were compared to interview reports to score for accuracy and omission of interview content. Results from both studies indicate that much interview information is lost between interview and report especially after a two-week delay. The majority of information reported by interviewers is accurate, although even interviewers who recalled information immediately after still reported a troubling amount of inaccurate information. Note-taking was found to increase accuracy and completeness of interviewer reports especially after a two week delay. Report type only influenced recall of interviewer questions. Experienced police interviewers were not any better at recalling a prior witness interview than student interviewers. Results emphasize the need to record witness interviews to allow for more accurate and complete interview reconstruction by interviewers, even if interview notes are available.

Elemental Analysis of Glass and Ink by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) and Laser Induced Breakdown Spectroscopy (LIBS)

The necessity of elemental analysis techniques to solve forensic problems continues to expand as the samples collected from crime scenes grow in complexity. Laser ablation ICP-MS (LA-ICP-MS) has been shown to provide a high degree of discrimination between samples that originate from different sources. In the first part of this research, two laser ablation ICP-MS systems were compared, one using a nanosecond laser and another a femtosecond laser source for the forensic analysis of glass. The results showed that femtosecond LA-ICP-MS did not provide significant improvements in terms of accuracy, precision and discrimination, however femtosecond LA-ICP-MS did provide lower detection limits. In addition, it was determined that even for femtosecond LA-ICP-MS an internal standard should be utilized to obtain accurate analytical results for glass analyses. In the second part, a method using laser induced breakdown spectroscopy (LIBS) for the forensic analysis of glass was shown to provide excellent discrimination for a glass set consisting of 41 automotive fragments. The discrimination power was compared to two of the leading elemental analysis techniques, µXRF and LA-ICP-MS, and the results were similar; all methods generated >99% discrimination and the pairs found indistinguishable were similar. An extensive data analysis approach for LIBS glass analyses was developed to minimize Type I and II errors en route to a recommendation of 10 ratios to be used for glass comparisons. Finally, a LA-ICP-MS method for the qualitative analysis and discrimination of gel ink sources was developed and tested for a set of ink samples. In the first discrimination study, qualitative analysis was used to obtain 95.6% discrimination for a blind study consisting of 45 black gel ink samples provided by the United States Secret Service. A 0.4% false exclusion (Type I) error rate and a 3.9% false inclusion (Type II) error rate was obtained for this discrimination study. In the second discrimination study, 99% discrimination power was achieved for a black gel ink pen set consisting of 24 self collected samples. The two pairs found to be indistinguishable came from the same source of origin (the same manufacturer and type of pen purchased in different locations). It was also found that gel ink from the same pen, regardless of the age, was indistinguishable as were gel ink pens (four pens) originating from the same pack.

Expertise Development in Volleyball: the Role of Early Sport Activities and Players’ Age and Height

The purpose of this study was to analyse the developmental pathway of skilled and less skilled volleyball players by focusing on the quantity and type of sporting activities, as well as their age and height in comparison to peers in those experiences. Retrospective interviews were conducted to provide a longitudinal and detailed account of sport involvement of 30 skilled and 30 less skilled volleyball players (15 male and 15 female players per group) throughout different developmental stages (stage 1: 8-12 years; stage 2: 13-16 years; stage 3: 17-20 years). Results indicated that the developmental pathway of these volleyball players (i.e. skilled and less skilled) was characterized by an early diversified sport involvement with a greater participation in sport activities during stages 1 and 2. However, skilled players specialized later in volleyball (between age 14 and 15) and performed more hours of volleyball at stage 3 (from 17 years of age onwards). Also, skilled players (male and female) were younger in both the diversified sport activities and volleyball at the later stages of development (i.e. stages 2 and 3), and skilled female players were taller than peers in those activities in the early stages of development (i.e. stages 1 and 2). The present findings suggest early diversification as a feasible pathway to reach expertise in volleyball and highlight the importance of practicing with older peers once specialization in the main sport has occurred. The findings highlight the need for coaches and sport programs to consider different stimuli existing within the training environment (i.e. characteristics of athletes, such as age and height) that influence the quality of practice and contribute to players’ expertise development.

International Sales of UK Television Content: Change and Continuity in ‘the space in between’ Production and Consumption

Focusing on the UK, this article addresses key issues facing the international distribution industry arising from over-the-top digital distribution and the fragmentation of audiences and revenues. Building on the identification of these issues, it investigates the extent to which UK distribution has altered over a ten-year period, pinpointing continuities in the destination and type of sales alongside changes in the role and structure of the industry as UK-based distributors adapt to a changing UK broadcasting landscape and global production environment. At one level increasing US ownership of UK-based distributors and the arrival of OTT players like Netflix, highlight the tensions between the national orientations of UK broadcasters and the global aspirations of independent producers and distributors. At another level VOD has boosted international sales of UK drama. Although the full impact of SVOD on content and rights has yet to materialise, significant changes in the industry predate the arrival of SVOD.

Combining histology, stable isotope analysis and ZooMS collagen fingerprinting to investigate the taphonomic history and dietary behaviour of extinct giant tortoises from the Mare aux Songes deposit on Mauritius

Taphonomic research of bones can provide additional insight into a site's formation and development, the burial environment and ongoing post-mortem processes. A total of 30 tortoise (Cylindraspis) femur bone samples from the Mare aux Songes site (Mauritius)were studied histologically, assessing parameters such as presence and type of microbial alteration, inclusions, staining/infiltrations, the degree of microcracking and birefringence. The absence of microbial attack in the 4200 year old Mare aux Songes bones suggests the animals rapidly entered the soil whole-bodied and were sealed anoxically, although they suffered frombiological and chemical degradation (i.e. pyrite formation/oxidation, mineral dissolution and staining) related to changes in the site's hydrology. Additionally, carbon and nitrogen stable isotopeswere analysed to obtain information on the animals' feeding behaviour. The results show narrowly distributed δ13C ratios, indicating a terrestrial C3 plant-based diet, combined with a wide range in δ15N ratios. This is most likely related to the tortoises' drought-adaptive ability to change their metabolic processes, which can affect the δ15N ratios. Furthermore, ZooMS collagen fingerprinting analysis successfully identified two tortoise species (C. triserrata and C. inepta) in the bone assemblage,which,when combined with stable isotope data, revealed significantly different δ15N ratios between the two tortoise species. As climatic changes around this period resulted in increased aridity in the Mascarene Islands, this could explain the extremely elevated δ15N ratio in our dataset. The endemic fauna was able to endure the climatic changes 4200 years ago, although human arrival in the 17th century changed the original habitat to such an extent that it resulted in the extinction of several species. Fortunately we are still able to study these extinct tortoises due to the beneficial conditions of their burial environment, resulting in excellent bone preservation.

Preparation of low protein latex : Effect of different cure systems and fillers on its properties

Natural rubber latex, an aqueous colloidal dispersion of polyisoprene is widely used in production of gloves, catherers, rubber bands etc. The natural rubber latex content present in products such as gloves causes allergic problems. Of the different types of allergies reported, latex is known to produce Type I and Type IV allergies. Type I is called immediate hypersensitivity and type IV is called delayed hypersensitivity. It has been reported that some of the proteins present in the latex are mainly responsible for the allergic reactions type I. Significant reduction in the allergic response (type I) of natural rubber latex can be achieved by the reduction in its protein content, however out of the total proteins present in the latex or latex film only a fraction is extractable. The major techniques employed to reduce protein content of latex include leaching, autoclaving, chlorination, use of proteolytic enzymes and use of non ionic surfactants. Sulphur vulcanization of dipped products is responsible for Type IV allergy. N-nitrosamine, a carcinogenic substance is produced as a result of sulphur vulcanization. Radiation vulcanization can be used as an alternative for sulphur vulcanization. The current research deals with techniques to reduce the allergy associated with latex products. To reduce the type I allergy, low protein latex is developed using polyethylene glycol, a non- ionic surfactant. The present study employs radiation vulcanization to eliminate type IV allergy. The effect of different cure systems and fillers on the properties of low protein latex is also investigated as a part of the study.

Genomics and virulence factors of Fusobacterium necrophorum

Fusobacterium necrophorum, a Gram negative, anaerobic bacterium, is a common cause of acute pharyngitis and tonsillitis and a rare cause of more severe infections of the head and neck. At the beginning of the project, there was no available genome sequence for F. necrophorum. The aim of this project was to sequence the F. necrophorum genome and identify and study its putative virulence factors contained using in silico and in vitro analysis. Type strains JCM 3718 and JCM 3724,F. necrophorum subspecies necrophorum (Fnn) and funduliforme (Fnf), respectively, and strain ARU 01 (Fnf), isolated from a patient with LS, were commercially sequenced by Roche 454 GS-FLX+ next generation sequencing and assembled into contigs using Roche GS Assembler. Sequence data was annotated semi-automatically, using the xBASE pipeline, BLASTp and Pfam. The F. necrophorum genome was determined to be approximately 2.1 – 2.3 Mb in size, with an estimated 1,950 ORFs and includes genes for a leukotoxin, ecotin, haemolysin, haemagglutinin, haemin receptor, adhesin and type Vb and Vc secretion systems. The prevalence of the leukotoxin gene was investigated in strains JCM 3718, JCM 3724 and ARU 01, as well as a clinical collection of 25 Fnf strains, identified using biochemical and molecular tests. The leukotoxin operon was found to be universal within the strain collection by PCR. HL-60 cells subjected to aliquots of concentrated high molecular weight culture supernatant, predicted to contain the secreted leukotoxins of strains JCM 3718, JCM 3724 and ARU 01, were killed in a dose-dependent manner. The cytotoxic effect of the leukotoxin against human donor white blood cells was also tested to validate the HL-60 assay. The differences in the results between the two assays were not statistically significant. Ecotin, a serine protease inhibitor, was found to be present in 100 % of the strain collection and had a highly conserved sequence with primary and secondary binding sites exposed on opposing sides of the protein. During enzyme inhibition studies, a purified recombinant F. necrophorum ecotin protein inhibited human neutrophil elastase, a protease that degrades bacteria at inflammation sites, and human plasma kallikrein, a component of the host clotting cascade. The recombinant ecotin also prolonged human plasma clotting times by up to 7-fold for the extrinsic pathway, and up to 40-fold for the intrinsic pathway. The genome sequence data provides important information about F. necrophorum type strains and enables comparative study between strains and subspecies. Results from the leukotoxin and ecotin assays can be used to build up an understanding of how the organism behaves during infection.

A County Response to the IDOT Study to Determine Alternative Primary and Secondary Road System Sizes, 1982

This response is prepared to provide the public and its elected representatives with certain information which we believe to be of importance in selecting the size and type of highway network to be supported by the people of Iowa.

Time-Dependent Deformation of Non-Composite and Composite Sand-Lightweight Prestressed Concrete Structures, Phase 1, HR-137, 1969

Presented in this report is an investigation of the use of "sand-lightweight" concrete in prestressed concrete structures. The sand-lightweight concrete consists of 100% sand substitution for fines, along with Idealite coarse and medium lightweight aggregate and Type I Portland Cement.

Patient-reported outcomes and visual acuity after 12 months of anti-VEGF-treatment for sight-threatening diabetic macular edema in a real world setting

Aims To examine objective visual acuity measured with ETDRS, retinal thickness (OCT), patient reported outcome and describe levels of glycated hemoglobin and its association with the effects on visual acuity in patients treated with anti-VEGF for visual impairment due to diabetic macular edema (DME) during 12 months in a real world setting. Methods In this cross-sectional study, 58 patients (29 females and 29 males; mean age, 68 years) with type 1 and type 2 diabetes diagnosed with DME were included. Medical data and two questionnaires were collected; an eye-specific (NEI VFQ-25) and a generic health-related quality of life questionnaire (SF-36) were used. Results The total patient group had significantly improved visual acuity and reduced retinal thickness at 4 months and remains at 12 months follow up. Thirty patients had significantly improved visual acuity, and 27 patients had no improved visual acuity at 12 months. The patients with improved visual acuity had significantly improved scores for NEI VFQ-25 subscales including general health, general vision, near activities, distance activities, and composite score, but no significant changes in scores were found in the group without improvements in visual acuity. Conclusions Our study revealed that anti-VEGF treatment improved visual acuity and central retinal thickness as well as patient-reported outcome in real world 12 months after treatment start.

Complications after laparoscopic Roux-en-Y gastric bypass: a diagnostic challenge. Report of three cases and review of the literature

The number of Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) procedures for morbid obesity and type 2 diabetes mellitus will increase worldwide, and therefore, an increase in perioperative morbidity can be anticipated. The authors present three cases based on different complications after LRYGB to demonstrate the diagnostic challenge that clinicians face in this particular group of patients. Also, a review of the literature covering the value of different imaging in these particular cases is provided by the authors. The role of imaging in the diagnostic process is discussed.

LUNG CANCER IN NEPAL: THE ROLE OF TRADITIONAL TOBACCO PRODUCTS AND COMBUSTION RELATED HOUSEHOLD AIR POLLUTION

The burden of chronic diseases such as cancer is increasing in low and middle income countries around the globe. Nepal, one of the world’s poorest countries, is no exception to this trend, with lung cancer as the leading causes of cancer deaths. Despite this, limited data is available on the environmental and behavioral risk factors that contribute to the lung cancer etiology in Nepal. The objectives of this dissertation are to: 1) investigate the ethnic differences in consumption of local tobacco products and their role in lung cancer risk in Nepal; 2) evaluate urinary metabolite of 1,3-butadiene as a biomarker of exposure to combustion related household air pollution (CRHAP); 3) investigate the association between CRHAP exposure and lung cancer risk using urinary metabolite of 1,3-butadiene as a biomarker of exposure; 4) investigate the association between CRHAP exposure and lung cancer risk using questionnaire based measure of exposure. Lung cancer cases (n=606) and frequency matched controls (N=606) were recruited from B.P. Koirala Memorial Cancer Hospital. We obtained biological samples and information on lifestyles including cooking habits and type of fuels used. We used liquid chromatograph tandem mass spectrometer (LC-MS/MS) to quantify urinary metabolites of 1,3-butadiene in urine samples. We employed a combination of logistic and linear regression models to detect any exposure-disease associations while controlling for known confounding variables. Overall, we found that ethnic groups in Nepal use different tobacco products that have different differing cancer potency -we observed the highest odds ratios for the traditional tobacco products. The biomarker analysis showed strong evidence that monohydroxybutyl mercapturic acid is associated with biomass fuel use among participants. However, we did not find significant association between urinary MHMBA and lung cancer risk. When we used questionnaire based measure of exposure to household air pollution, we observed significant, dose-response associations between CRHAP exposure and lung cancer risk, particularly among never-smokers. Our results show that important role of local tobacco products in lung cancer risk in Nepal. Furthermore, we demonstrate that CRHAP exposure is a risk factor for lung cancer risk, independent of tobacco smoking.

Strategic tillage in no-till farming systems in Australia's northern grains-growing regions: I. Drivers and implementation

Development of no-tillage (NT) farming has revolutionized agricultural systems by allowing growers to manage greater areas of land with reduced energy, labour and machinery inputs to control erosion, improve soil health and reduce greenhouse gas emission. However, NT farming systems have resulted in a build-up of herbicide-resistant weeds, an increased incidence of soil- and stubble-borne diseases and enrichment of nutrients and carbon near the soil surface. Consequently, there is an increased interest in the use of an occasional tillage (termed strategic tillage, ST) to address such emerging constraints in otherwise-NT farming systems. Decisions around ST uses will depend upon the specific issues present on the individual field or farm, and profitability and effectiveness of available options for management. This paper explores some of the issues with the implementation of ST in NT farming systems. The impact of contrasting soil properties, the timing of the tillage and the prevailing climate exert a strong influence on the success of ST. Decisions around timing of tillage are very complex and depend on the interactions between soil water content and the purpose for which the ST is intended. The soil needs to be at the right water content before executing any tillage, while the objective of the ST will influence the frequency and type of tillage implement used. The use of ST in long-term NT systems will depend on factors associated with system costs and profitability, soil health and environmental impacts. For many farmers maintaining farm profitability is a priority, so economic considerations are likely to be a primary factor dictating adoption. However, impacts on soil health and environment, especially the risk of erosion and the loss of soil carbon, will also influence a grower's choice to adopt ST, as will the impact on soil moisture reserves in rainfed cropping systems. © 2015 Elsevier B.V.

Fluorine-18-labeled estrogens, progestins and corticosteroids for receptor-based imaging of breast tumors and target areas of the brain

Estrogens can be labeled with the positron-emitting radionuclide fluorine-18 (t$\sb{1/2}$ = 110 min) by fluoride ion (n-Bu$\sb4$N$\sp{18}$F) displacement of a 16$\beta$-trifluoromethanesulfonate (triflate) derivative of the corresponding estrone 3-triflate, and purification by HPLC. That sequence has been used to synthesize the 11$\beta$-methoxy 1 and 11$\beta$-ethyl 2 analogues of the breast tumor imaging agent, 16$\alpha$-($\sp{18}$F) fluoro-17$\beta$-estradiol (FES). Tissue distribution studies of 1 and 2 in immature female rats show high selectivity for target tissue (T, uterus) vs non-target (NT, muscle and lung), with T/NT ratios being 43 and 17 at one hour after injection for 1 and 2, respectively. The parent estrogen FES has previously been shown to display an intermediate value for tissue selectivity.