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Female fertility is a complex trait with age-specific changes in spontaneous dizygotic (DZ) twinning and fertility. To elucidate factors regulating female fertility and infertility, we conducted a genome-wide association study (GWAS) on mothers of spontaneous DZ twins (MoDZT) versus controls (3273 cases, 24,009 controls). This is a follow-up study to the Australia/New Zealand (ANZ) component of that previously reported (Mbarek et al., 2016), with a sample size almost twice that of the entire discovery sample meta-analysed in the previous article (and five times the ANZ contribution to that), resulting from newly available additional genotyping and representing a significant increase in power. We compare analyses with and without male controls and show unequivocally that it is better to include male controls who have been screened for recent family history, than to use only female controls. Results from the SNP based GWAS identified four genomewide significant signals, including one novel region, ZFPM1 (Zinc Finger Protein, FOG Family Member 1), on chromosome 16. Previous signals near FSHB (Follicle Stimulating Hormone beta subunit) and SMAD3 (SMAD Family Member 3) were also replicated (Mbarek et al., 2016). We also ran the GWAS with a dominance model that identified a further locus ADRB2 on chr 5. These results have been contributed to the International Twinning Genetics Consortium for inclusion in the next GWAS meta-analysis (Mbarek et al., in press).
Negative emotionality (NE) was evaluated as a candidate mechanism linking prenatal maternal affective symptoms and offspring internalizing problems during the preschool/early school age period. The participants were 335 mother–infant dyads from the Maternal Adversity, Vulnerability and Neurodevelopment project. A Confirmatory Bifactor Analysis (CFA) based on self-report measures of prenatal depression and pregnancy-specific anxiety generated a general factor representing overlapping symptoms of prenatal maternal psychopathology and four distinct symptom factors representing pregnancy-specific anxiety, negative affect, anhedonia and somatization. NE was rated by the mother at 18 and 36 months. CFA based on measures of father, mother, child-rated measures and a semistructured interview generated a general internalizing factor representing overlapping symptoms of child internalizing psychopathology accounting for the unique contribution of each informant. Path analyses revealed significant relationships among the general maternal affective psychopathology, the pregnancy- specific anxiety, and the child internalizing factors. Child NE mediated only the relationship between pregnancy-specific anxiety and the child internalizing factors. We highlighted the conditions in which prenatal maternal affective symptoms predicts child internalizing problems emerging early in development, including consideration of different mechanistic pathways for different maternal prenatal symptom presentations and child temperament.
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.
Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).
Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
We present the data and initial results from the first pilot survey of the Evolutionary Map of the Universe (EMU), observed at 944 MHz with the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. The survey covers
of an area covered by the Dark Energy Survey, reaching a depth of 25–30
rms at a spatial resolution of
11–18 arcsec, resulting in a catalogue of
220 000 sources, of which
180 000 are single-component sources. Here we present the catalogue of single-component sources, together with (where available) optical and infrared cross-identifications, classifications, and redshifts. This survey explores a new region of parameter space compared to previous surveys. Specifically, the EMU Pilot Survey has a high density of sources, and also a high sensitivity to low surface brightness emission. These properties result in the detection of types of sources that were rarely seen in or absent from previous surveys. We present some of these new results here.
Hookworms are some of the most widespread of the soil-transmitted helminths (STH) with an estimated 438.9 million people infected. Until relatively recently Ancylostoma ceylanicum was regarded as a rare cause of hookworm infection in humans, with little public health relevance. However, recent advances in molecular diagnostics have revealed a much higher prevalence of this zoonotic hookworm than previously thought, particularly in Asia. This study examined the prevalence of STH and A. ceylanicum in the municipalities of Palapag and Laoang in the Philippines utilizing real-time polymerase chain reaction (PCR) on stool samples previously collected as part of a cross-sectional survey of schistosomiasis japonica. Prevalence of hookworm in humans was high with 52.8% (n = 228/432) individuals positive for any hookworm, 34.5% (n = 149/432) infected with Necator americanus, and 29.6% (n = 128/432) with Ancylostoma spp; of these, 34 were PCR-positive for A. ceylanicum. Considering dogs, 12 (n = 33) were PCR-positive for A. ceylanicum. This is the first study to utilize molecular diagnostics to identify A. ceylanicum in the Philippines with both humans and dogs infected. Control and elimination of this zoonotic hookworm will require a multifaceted approach including chemotherapy of humans, identification of animal reservoirs, improvements in health infrastructure, and health education to help prevent infection.
Reading and language abilities are critical for educational achievement and success in adulthood. Variation in these traits is highly heritable, but the underlying genetic architecture is largely undiscovered. Genetic studies of reading and language skills traditionally focus on children with developmental disorders; however, much larger unselected adult samples are available, increasing power to identify associations with specific genetic variants of small effect size. We introduce an Australian adult population cohort (41.7–73.2 years of age, N = 1505) in which we obtained data using validated measures of several aspects of reading and language abilities. We performed genetic association analysis for a reading and spelling composite score, nonword reading (assessing phonological processing: a core component in learning to read), phonetic spelling, self-reported reading impairment and nonword repetition (a marker of language ability). Given the limited power in a sample of this size (~80% power to find a minimum effect size of 0.005), we focused on analyzing candidate genes that have been associated with dyslexia and developmental speech and language disorders in prior studies. In gene-based tests, FOXP2, a gene implicated in speech/language disorders, was associated with nonword repetition (p < .001), phonetic spelling (p = .002) and the reading and spelling composite score (p < .001). Gene-set analyses of candidate dyslexia and speech/language disorder genes were not significant. These findings contribute to the assessment of genetic associations in reading and language disorders, crucial for understanding their etiology and informing intervention strategies, and validate the approach of using unselected adult samples for gene discovery in language and reading.
Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.
Schistosomiasis in China has been substantially reduced due to an effective control programme employing various measures including bovine and human chemotherapy, and the removal of bovines from endemic areas. To fulfil elimination targets, it will be necessary to identify other possible reservoir hosts for Schistosoma japonicum and include them in future control efforts. This study determined the infection prevalence of S. japonicum in rodents (0–9·21%), dogs (0–18·37%) and goats (6·9–46·4%) from the Dongting Lake area of Hunan province, using a combination of traditional coproparasitological techniques (miracidial hatching technique and Kato-Katz thick smear technique) and molecular methods [quantitative real-time PCR (qPCR) and droplet digital PCR (ddPCR)]. We found a much higher prevalence in goats than previously recorded in this setting. Cattle and water buffalo were also examined using the same procedures and all were found to be infected, emphasising the occurrence of active transmission. qPCR and ddPCR were much more sensitive than the coproparasitological procedures with both KK and MHT considerably underestimating the true prevalence in all animals surveyed. The high level of S. japonicum prevalence in goats indicates that they are likely important reservoirs in schistosomiasis transmission, necessitating their inclusion as targets of control, if the goal of elimination is to be achieved in China.
The current World Health Organization strategic plan targets the elimination of schistosomiasis as a public health problem by 2025 and accurate diagnostics will play a pivotal role in achieving this goal. DNA-based detection methods provide a viable alternative to some of the commonly used tests, notably microscopy and serology, for the diagnosis of schistosomiasis. The detection of parasite cell-free DNA in different clinical samples is a recent valuable advance, which provides significant benefits for accurate disease diagnosis. Here we validated a novel duplex droplet digital PCR assay for the diagnosis of Chinese (SjC) and Philippine (SjP) strains of Schistosoma japonicum infection in a mouse model. The assay proved applicable for both SjC and SjP infections and capable of detecting infection at a very early intra-mammalian stage in conveniently obtainable samples (urine and saliva) as well as in serum and feces. The target DNA copy numbers obtained in the assay showed a positive correlation with the infection burden assessed by direct traditional parasitology. The potential to detect parasite DNA in urine and saliva has important practical implications for large-scale epidemiological screening programmes in the future, particularly in terms of logistical convenience, and the assay has the potential to be a valuable additional tool for the diagnosis of schistosomiasis japonica.
Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.
The previous chapter sets out how the distress children experience when exposed to conflict between parents can translate into long-term difficulties, including emotional and behavioural problems, troubled relationships and failure to settle and achieve at school (e.g. see Rhoades, 2008; Cummings and Davies, 2010). As the body of research documenting an association between a high conflict home and poor outcomes for children has grown, over the last decade research attention has turned to examining the mechanisms that explain these poor outcomes, the focus of this current chapter. Explanations fall broadly into two categories. First, inter-parental conflict affects parenting and the quality of the relationship between parent and child (i.e. conflict between parents ‘spills over’ to the parent–child relationship). Secondly, children's negative cognitive and emotional responses to conflict, including how they represent or perceive family relationships, make them vulnerable to adjustment difficulties.
Inter-parental conflict and troubled family relationships
One of the ways that inter-parental conflict influences children's adjustment is through its impact on parenting and the parent–child relationship (Schoppe-Sullivan et al., 2007; Cox et al., 2001; Erel and Burman, 1995). Distress in the couple relationship can be expressed through a range of unhelpful parenting behaviours, from highly intrusive and harsh parenting through to lax, inconsistent and emotionally unavailable parenting.
Harsh discipline and intrusive parenting
In keeping with a ‘spillover’ hypothesis, suggesting that negative emotions in the couple relationship spill over to the parent–child relationship(s), parenting in high conflict homes can be characterised by aggression, criticism, verbal and physical threat, yelling, hitting and shoving (Holden and Ritchie, 1991; Jenkins and Smith, 1991). A body of evidence links harsh parenting to children's externalising (Gonzales et al., 2000; Buehler and Gerard, 2002; Buehler et al., 2006; Benson et al., 2008; Harold et al., 2012) and internalising problems (Doyle and Markiewicz, 2005; Buehler et al., 2006) arising out of conflict between parents. Parents may also become psychologically controlling – attempting to influence children's thoughts, feelings and attitudes in line with their own expectations – again with deleterious outcomes for children (Krishnakumar et al., 2003; Doyle and Markiewicz, 2005; Buehler et al., 2006; Schoppe-Sullivan et al., 2007).
This chapter explores the implications of the findings presented in the last chapter on couple interventions. It aims to highlight what this means for those working with families in trying to help parents manage their conflict and avoid its potentially harmful influence on children. The limitations of current intervention research and new innovative ideas for dealing with inter-parental conflict are also highlighted in this chapter.
When should we intervene?
Early intervention is believed to offer benefits in longterm outcomes and is considered to be more effective than treatment-based interventions, which are provided once problems arise (Rutter, 2010). Many of the programmes presented in the last chapter focus on a prevention-based approach by identifying couples and families who may be at risk of experiencing higher stress and couple disagreement, rather than those who are already characterised by entrenched levels of conflict. Even the programmes aimed at separated and divorced parents predominately target those with a more normative and less extreme conflict style (McIntosh and Deacon-Wood, 2003). It is widely recognised that behaviour change is greater and more sustainable with earlier intervention, rather than trying to change ingrained and longstanding patterns of interaction (Dolan et al., 2010).
Early intervention is important, but how early is early enough?
The evidence from relationship education or preparation programmes indicates that couple interventions have traditionally been applied to couples entering marriage. Entry to marriage represents a key time for intervention as some couples may face significant challenges as they adapt to the changes and new commitment in their relationship. However, for many couples, marriage may not represent the beginning of a relationship in the same way as it did in the past. The majority of couples now cohabit before marriage and a growing number also have a child or children outside of marriage (Hunt, 2009; Lloyd and Lacey, 2012). These changes in relationship formation mean that interventions are also offered during other transition points and life course changes, such as the transition to parenthood.
A diverse and flexible approach of when to target relationship intervention may be best in order to reach couples when they are more receptive to help and support, and perhaps more motivated to change behaviours if necessary (Halford, 2004; Hawkins et al., 2004; Cowan et al., 2010).