Low temperature impact strength of heavy section ductile iron castings: effects of microstructure and chemical composition

A foundry research project has been recently initiated at RTIT in order to better understand the fabrication of as-cast heavy section DI parts meeting high impact energy requirements at low temperatures. The experimental castings have the following dimensions 180 mm x 180 mm x 190 mm. The achieved as-cast Charpy impact strengths were as follows: 17 J (RT), 16 J (-20°C) and 11 J (-40°C). The foundry process, the chemical composition and the microstructure of this experimental casting are compared to the ones of various examples in order to show the detrimental effects of residual elements, microshrinkage and microcarbide on the impact properties. Finally, quality index empirical models (based on casting chemical compositions) are used to analyse the impact tests results. This paper illustrates that an adequate nodule count can contribute to reducing the detrimental effects of the residual elements and microsegregation

Frequency and patterns of early recanalization after vasectomy

BACKGROUND: Our understanding of early post-vasectomy recanalization is limited to histopathological studies. The objective of this study was to estimate the frequency and to describe semen analysis patterns of early recanalization after vasectomy. METHODS: Charts displaying serial post-vasectomy semen analyses were created using the semen analysis results from 826 and 389 men participating in a randomized trial of fascial interposition (FI) and an observational study of cautery, respectively. In the FI trial, participants were randomly allocated to vas occlusion by ligation and excision with or without FI. In the cautery study, sites used their usual cautery occlusion technique, two with and two without FI. Presumed early recanalization was based on the assessment of individual semen analysis charts by three independent reviewers. Discrepancies were resolved by consensus. RESULTS: Presumed early recanalization was characterized by a very low sperm concentration within two weeks after vasectomy followed by return to large numbers of sperm over the next few weeks. The overall proportion of men with presumed early recanalization was 13% (95% CI 12%–15%). The risk was highest with ligation and excision without FI (25%) and lowest for thermal cautery with FI (0%). The highest proportion of presumed early recanalization was observed among men classified as vasectomy failures. CONCLUSION: Early recanalization, occurring within the first weeks after vasectomy, is more common than generally recognized. Its frequency depends on the occlusion technique performed

Distinct Roles for Aryl Hydrocarbon Receptor Nuclear Translocator and Ah Receptor in Estrogen-Mediated Signaling in Human Cancer Cell Lines

The activated AHR/ARNT complex (AHRC) regulates the expression of target genes upon exposure to environmental contaminants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Importantly, evidence has shown that TCDD represses estrogen receptor (ER) target gene activation through the AHRC. Our data indicates that AHR and ARNT act independently from each other at non-dioxin response element sites. Therefore, we sought to determine the specific functions of AHR and ARNT in estrogen-dependent signaling in human MCF7 breast cancer and human ECC-1 endometrial carcinoma cells. Knockdown of AHR with siRNA abrogates dioxin-inducible repression of estrogen-dependent gene transcription. Intriguingly, knockdown of ARNT does not effect TCDD-mediated repression of estrogen-regulated transcription, suggesting that AHR represses ER function independently of ARNT. This theory is supported by the ability of the selective AHR modulator 3′,4′-dimethoxy-α-naphthoflavone (DiMNF) to repress estrogen-inducible transcription. Furthermore, basal and estrogen-activated transcription of the genes encoding cathepsin-D and pS2 are down-regulated in MCF7 cells but up-regulated in ECC-1 cells in response to loss of ARNT. These responses are mirrored at the protein level with cathepsin-D. Furthermore, knock-down of ARNT led to opposite but corresponding changes in estrogen-stimulated proliferation in both MCF7 and ECC-1 cells. We have obtained experimental evidence demonstrating a dioxin-dependent repressor function for AHR and a dioxin-independent co-activator/co-repressor function for ARNT in estrogen signalling. These results provide us with further insight into the mechanisms of transcription factor crosstalk and putative therapeutic targets in estrogen-positive cancers

Limitations of variable number of tandem repeat typing identified through whole genome sequencing of Mycobacterium avium subsp. paratuberculosis on a national and herd level

Background: Mycobacterium avium subsp. paratuberculosis (MAP), the causative bacterium of Johne’s disease in dairy cattle, is widespread in the Canadian dairy industry and has significant economic and animal welfare implications. An understanding of the population dynamics of MAP can be used to identify introduction events, improve control efforts and target transmission pathways, although this requires an adequate understanding of MAP diversity and distribution between herds and across the country. Whole genome sequencing (WGS) offers a detailed assessment of the SNP-level diversity and genetic relationship of isolates, whereas several molecular typing techniques used to investigate the molecular epidemiology of MAP, such as variable number of tandem repeat (VNTR) typing, target relatively unstable repetitive elements in the genome that may be too unpredictable to draw accurate conclusions. The objective of this study was to evaluate the diversity of bovine MAP isolates in Canadian dairy herds using WGS and then determine if VNTR typing can distinguish truly related and unrelated isolates.<p></p> Results: Phylogenetic analysis based on 3,039 SNPs identified through WGS of 124 MAP isolates identified eight genetically distinct subtypes in dairy herds from seven Canadian provinces, with the dominant type including over 80% of MAP isolates. VNTR typing of 527 MAP isolates identified 12 types, including “bison type” isolates, from seven different herds. At a national level, MAP isolates differed from each other by 1–2 to 239–240 SNPs, regardless of whether they belonged to the same or different VNTR types. A herd-level analysis of MAP isolates demonstrated that VNTR typing may both over-estimate and under-estimate the relatedness of MAP isolates found within a single herd.<p></p> Conclusions: The presence of multiple MAP subtypes in Canada suggests multiple introductions into the country including what has now become one dominant type, an important finding for Johne’s disease control. VNTR typing often failed to identify closely and distantly related isolates, limiting the applicability of using this typing scheme to study the molecular epidemiology of MAP at a national and herd-level.<p></p&gt

Migration patterns of Culex fatigans around Delhi, India

デリー周辺の村においてはネッタイイエカは村をとりかこむ畑地の中の井戸に生息している.井戸から村への蚊の移動をしらべるため,標識した蚊をいろいろな距離から放した.村から250m以内にある井戸から放した蚊の大部分は村に飛来した.500mの距離で放したものは約18%が村に飛来したと推定された.1000mの距離では約8%であった.村の中心部でとらえた蚊は主として人間の血を吸っていたが,村の周辺部では鳥の血を吸った個体が多くなり,特に村の外で捕えた蚊のほとんどは鳥の血を吸っていた.Under rural conditions Culex fatigans breeds in wells located in fields surrounding the villages. The migration of mosquitos from the wells to the village was determined by releasing marked individuals at various distances from the village. Nearly all mosquitos released at wells situated within a 250m distance from the village migrated to it. About 18% of the mosquitos released at a distance of 500m and about 8% of those released at 1000m from the village also migrated to it. Blood in the gut of mosquitos collected in the late spring-early summer showed that those collected within the villages fed principally on humans, whereas a high proportion of those collected in the adjoining fields fed on birds

Reducing behavior problems in children born after an unintended pregnancy:the generation R study

Objectives: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. Methods: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support. Results: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems. Conclusions: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention.</p

Reducing behavior problems in children born after an unintended pregnancy:the generation R study

Objectives: To examine differences in behavior problems between children from intended versus unintended pregnancies, and to estimate how much the difference in problem behavior would be reduced if postnatal depression was eliminated and social support was increased within 6 months after birth. Methods: Data from the Generation R Study were used, a population-based birth cohort in Rotterdam, the Netherlands (N = 9621). Differences in child internalizing and externalizing behavior at ages 1.5, 3, 6, 9 and 13 years between pregnancy intention groups were estimated using linear regression. Associations of postnatal depression and social support with internalizing and externalizing problems were also estimated using linear regression. Child behavior outcomes where compared before and after modelling a situation in which none of the mothers experienced a postnatal depression and all mother experienced high social support. Results: Most pregnancies (72.9%) were planned, 14.8% were unplanned and wanted, 10.8% were unplanned with initially ambivalent feelings and 1.5% with prolonged ambivalent feelings. Children from unplanned pregnancies had more internalizing and externalizing problems at all ages as compared to children from a planned pregnancy, especially when ambivalent feelings were present. Hypothetically eliminating on postnatal depression reduced the differences in internalizing and externalizing problems by 0.02 to 0.16 standard deviation. Hypothetically increasing social support did not significantly reduce the difference in internalizing and externalizing problems. Conclusions: Children from an unplanned pregnancy have more behavior problems, in particular when mothers had prolonged ambivalent feelings. Eliminating postnatal depression may help to reduce the inequality in child behavior related to pregnancy intention.</p

Pathology-confirmed versus non pathology-confirmed cancer diagnoses: incidence, participant characteristics, and survival

Cancer diagnoses which are not confirmed by pathology are often under-registered in cancer registries compared to pathology-confirmed diagnoses. It is unknown how many patients have a non pathology-confirmed cancer diagnosis, and whether their characteristics and survival differ from patients with a pathology-confirmed diagnosis. Participants from the prospective population-based Rotterdam Study were followed between 1989 and 2013 for the diagnosis of cancer. Cancer diagnoses were classified into pathology-confirmed versus non pathology-confirmed (i.e., based on imaging or tumour markers). We compared participant characteristics and the distribution of cancers at different sites. Furthermore, we investigated differences in overall survival using survival curves adjusted for age and sex. During a median (interquartile range) follow-up of 10.7 (6.3–15.9) years, 2698 out of 14,024 participants were diagnosed with cancer, of which 316 diagnoses (11.7%) were non pathology-confirmed. Participants with non pathology-confirmed diagnoses were older, more often women, and had a lower education. Most frequently non pathology-confirmed cancer sites included central nervous system (66.7%), hepato-pancreato-biliary (44.5%), and unknown primary origin (31.2%). Survival of participants with non pathology-confirmed diagnoses after 1 year was lower compared to survival of participants with pathology-confirmed diagnoses (32.6% vs. 63.4%; risk difference of 30.8% [95% CI 25.2%; 36.2%]). Pathological confirmation of cancer is related to participant characteristics and cancer site. Furthermore, participants with non pathology-confirmed diagnoses have worse survival than participants with pathology-confirmed diagnoses. Missing data on non pathology-confirmed diagnoses may result in underestimation of cancer incidence and in an overestimation of survival in cancer registries, and may introduce bias in aetiological research

Making Drug Approval Decisions in the Face of Uncertainty:Cumulative Evidence versus Value of Information

Background: The COVID-19 pandemic underscored the criticality and complexity of decision making for novel treatment approval and further research. Our study aims to assess potential decision-making methodologies, an evaluation vital for refining future public health crisis responses. Methods: We compared 4 decision-making approaches to drug approval and research: the Food and Drug Administration’s policy decisions, cumulative meta-analysis, a prospective value-of-information (VOI) approach (using information available at the time of decision), and a reference standard (retrospective VOI analysis using information available in hindsight). Possible decisions were to reject, accept, provide emergency use authorization, or allow access to new therapies only in research settings. We used monoclonal antibodies provided to hospitalized COVID-19 patients as a case study, examining the evidence from September 2020 to December 2021 and focusing on each method’s capacity to optimize health outcomes and resource allocation. Results: Our findings indicate a notable discrepancy between policy decisions and the reference standard retrospective VOI approach with expected losses up to $269 billion USD, suggesting suboptimal resource use during the wait for emergency use authorization. Relying solely on cumulative meta-analysis for decision making results in the largest expected loss, while the policy approach showed a loss up to$16 billion and the prospective VOI approach presented the least loss (up to $2 billion). Conclusion: Our research suggests that incorporating VOI analysis may be particularly useful for research prioritization and treatment implementation decisions during pandemics. While the prospective VOI approach was favored in this case study, further studies should validate the ideal decision-making method across various contexts. This study’s findings not only enhance our understanding of decision-making strategies during a health crisis but also provide a potential framework for future pandemic responses. This study reviews discrepancies between a reference standard (retrospective VOI, using hindsight information) and 3 conceivable real-time approaches to research-treatment decisions during a pandemic, suggesting suboptimal use of resources. Of all prospective decision-making approaches considered, VOI closely mirrored the reference standard, yielding the least expected value loss across our study timeline. This study illustrates the possible benefit of VOI results and the need for evidence accumulation accompanied by modeling in health technology assessment for emerging therapies.</p