Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study

OBJECTIVES: This study investigated the influence of mother's age at menopause, early life and adult behavioral factors on the timing of menopause until age 57 years, and whether these effects vary according to the women's age at menopause. DESIGN: A nationally representative cohort of 1,583 British women born in March 1946 with prospective data across the life course. For factors that vary with age at menopause, analyses were stratified by age at menopause younger than 50 years or 50 years or older. RESULTS: Cox regression models indicated that for women with earlier menopause, those who were heaviest at 2 years had a 59% lower hazard ratio for menopause than those who were the lightest (hazard ratio [HR]=0.41, 95% CI: 0.16-1.01), whereas this figure was 35% lower (HR=0.65; 95% CI: 0.42-1.00) for the later menopause group. For women in the earlier group with parental divorce during childhood, the HR was 6.5 (95% CI: 2.021.3) times higher than that of other women. This rate decreased to 2.5 (95% CI: 1.5-4.2) for those with later menopause. In both groups, increasing mother's age at menopause was associated with decreasing HR (P<0.0001). For all women, being breast-fed (P=0.05), increasing cognitive ability (P=0.009), and increasing parity (P=0.001) delayed menopause. CONCLUSIONS: This study found that the impact of weight at 2 years, parental divorce during childhood, and mother's age at menopause varied according to the women's age at menopause. There was further evidence that being breast-fed, higher childhood cognitive ability, and increasing parity delayed menopause. These results suggest the interaction of genetic and environmental factors in determining age at menopause.     

Does early indoor microbial exposure reduce the risk of asthma? The Prevention and Incidence of Asthma and Mite Allergy birth cohort study

BACKGROUND: Exposure to microbial agents might inhibit the development of atopy and asthma. OBJECTIVE: We measured the association between microbial exposure assessed at 3 months and the development of atopic sensitization and doctor-diagnosed (DD) asthma and wheeze in the first 4 years in a birth cohort study of children with atopic mothers. METHODS: Endotoxin, fungal (1-->3)-beta-D-glucans, extracellular polysaccharides from the genera Penicillium and Aspergillus (EPS-Pen/Asp), and dust on living room floors were measured at 3 months of age. Serum IgE levels against common allergens were determined at 1 and 4 years, and questionnaire information about respiratory morbidity was collected yearly. RESULTS: Microbial levels in mattresses were low and not associated with serum IgE levels, DD asthma, and wheeze. Floor levels of biocontaminants and dust, on the other hand, were inversely associated with DD asthma, being most pronounced for endotoxin (odds ratio [OR], 0.40; 95% CI, 0.21-0.77) and EPS-Pen/Asp (OR, 0.42; 95% CI, 0.18-0.99). Mutual adjustment for other exposures did not significantly alter the results for endotoxin and only moderately affected the results for EPS-Pen/Asp. Persistent wheeze was also consistently less common in the high-exposure group, being significant only for EPS-Pen/Asp (OR, 0.37; 95% CI, 0.15-0.96). Transient wheeze and wheeze in the past 12 months were also reduced, but effects were smaller and not significant. Relationships with serum-specific IgE levels, which could only be assessed in 41% at age 4 years, were less pronounced and statistically significant only for EPS-Pen/Asp. CONCLUSIONS: Early exposure to common microbial contaminants, including fungal agents, might protect against asthma. CLINICAL IMPLICATIONS: Microbial exposure in early life might protect against asthma and might constitute a novel target for prevention.     

The growth of assisted reproductive treatment-conceived children from birth to 5 years: a national cohort study

Background

Birth weight and early child growth are important predictors of long-term cardiometabolic disease risk, in line with the Developmental Origins of Health and Disease hypothesis. As human assisted reproductive technologies (ARTs) occur during the sensitive periconceptional window of development, it has recently become a matter of urgency to investigate risk in ART-conceived children.

Methods

We have conducted the first large-scale, national cohort study of early growth in ART children from birth to school age, linking the register of ART, held by the UK’s Human Fertilisation and Embryology Authority, to Scottish maternity and child health databases.

Results

In this study of 5200 ART and 20,800 naturally conceived (NC) control children, linear regression analysis revealed the birthweight of babies born from fresh embryo transfer cycles is 93.7 g [95% CI (76.6, 110.6)g] less than NC controls, whereas babies born from frozen embryo transfer (FET) cycles are 57.5 g [95% CI (30.7, 86.5)g] heavier. Fresh ART babies grew faster from birth (by 7.2 g/week) but remained lighter (by 171 g), at 6–8 weeks, than NC babies and 133 g smaller than FET babies; FET and NC babies were similar. Length and occipital-frontal circumference followed the same pattern. By school entry (4–7 years), weight, length and BMI in boys and girls conceived by fresh ART and FET were similar to those in NC children.

Conclusions

ART babies born from fresh embryo transfer grow more slowly in utero and in the first few weeks of life, but then show postnatal catch up growth by school age, compared to NC and FET babies. As low birth weight and postnatal catch-up are independent risk factors for cardiometabolic disease over the life-course, we suggest that further studies in this area are now warranted.

     

Does pay-for-performance influence the quality of care?

PURPOSE OF REVIEW: To summarize studies of pay-for-performance programmes designed to address clinical quality of care markers in ambulatory settings at the level of the physician group or individual physician. RECENT FINDINGS: Seven randomized controlled trials and 15 nonrandomized studies were reviewed. Less than half of the randomized controlled trials showed positive results, whereas all but one of the nonrandomized studies showed positive or mixed results. Characteristics of the quality measures, incentives, providers, patients, and concurrent interventions probably influenced the results. Study methodology problems such as small sample sizes, selection bias, and inadequate control for confounders were common. Asthma quality of care markers were included in three nonrandomized studies, two of which showed positive results and one of which was negative. SUMMARY: The data reviewed in this article suggest that pay-for-performance programmes can improve markers of quality, though not always. Even when studies suggest positive effects, the designs often do not permit assurance that the effects are due to the incentives as compared with other factors. More and better-designed studies are needed to determine the actual effectiveness of incentives themselves isolated from other factors, circumstances that promote effectiveness, effectiveness relative to other strategies, and cost-effectiveness.     

Does planning a different trajectory influence the choice of grasping points?

We examined whether the movement path is considered when selecting the positions at which the digits will contact the object’s surface (grasping points). Subjects grasped objects of different heights but with the same radius at various locations on a table. At some locations, one digit crossed to the side of the object opposite of where it started. In doing so, it moved over a short object whereas it curved around a tall object. This resulted in very different paths for different objects. Importantly, the selection of grasping points was unaffected. That subjects do not appear to consider the path when selecting grasping points suggests that the grasping points are selected before planning the movements towards those points.     

Does the error negativity reflect response conflict strength? Evidence from a Simon task

The error (-related) negativity (Ne or ERN) has been related to detecting the mismatch between incorrectly executed and appropriate responses or, alternatively, to the degree of conflict between different response alternatives. In this study different levels of response conflict were generated by manipulating task difficulty in a Simon task. According to the product of incorrect and subsequent correct EMG activation, the amount of conflict in error trials was indeed larger for the easy than for the hard condition. In contrast, Ne/ERN amplitudes did not differ between difficulty conditions, nor was the amount of conflict mirrored by Ne/ERN amplitude. Therefore, the present data are at variance with the hypothesis that the Ne/ERN reflects the degree of response conflict.     

Do we have a common mechanism for measuring time in the hundreds of millisecond range? Evidence from multiple-interval timing tasks

In the present study we examined the performance variability of a group of 13 subjects in eight different tasks that involved the processing of temporal intervals in the subsecond range. These tasks differed in their sensorimotor processing (S; perception vs. production), the modality of the stimuli used to define the intervals (M; auditory vs. visual), and the number of intervals (N; one or four). Different analytical techniques were used to determine the existence of a central or distributed timing mechanism across tasks. The results showed a linear increase in performance variability as a function of the interval duration in all tasks. However, this compliance of the scalar property of interval timing was accompanied by a strong effect of S, N, and M and the interaction between these variables on the subjects' temporal accuracy. Thus the performance variability was larger not only in perceptual tasks than that in motor-timing tasks, but also using visual rather than auditory stimuli, and decreased as a function of the number of intervals. These results suggest the existence of a partially overlapping distributed mechanism underlying the ability to quantify time in different contexts.     

Does a single session of Attentional Bias Modification influence early neural mechanisms of spatial attention? An ERP study

A relatively new cognitive‐affective training procedure, the Attentional Bias Modification (ABM) technique, is thought to decrease biases in the allocation of attention toward negative emotional stimuli. In two studies, we tested in samples of healthy students whether a single session of ABM has an influence on early orienting of spatial attention as indexed by the N2pc. Replicating previous studies, we found an occipitotemporal N2pc (180–300 ms) contralateral to angry versus neutral facial expressions, indicating that threatening faces automatically draw attention in early stages of stimulus processing. However, this N2pc effect did not significantly change during the ABM training session. Our results therefore indicate that a single session of ABM does not affect early attentional orienting. ABM effects reported in prior research may therefore have been mediated by later cognitive‐affective mechanisms.     

Fertilization and early embryology: Does zona pellucida thickness influence the fertilization rate?

In human in-vitro fertilization (IVF), the cumulus oophorusis routinely removed to assess fertilization and hence the thicknessof the zona pellucida is measurable. This study aimed to measurethe thickness of the zona pellucida and to assess its influenceon fertilization rate in IVF programmes. The zona pellucidathickness varies from 10 to 31 µm with a mean of 17.5µm. One-way analysis of variance revealed that in IVFtrials performed with normal semen, the zona pellucida of fertilizedoocytes (16.6 ± 3.2 µm) was significantly thinnerthan the zona pellucida of unfertilized oocytes (18.9 ±4.0 µm; P < 0.001). As measured on micro-injected oocytes,the zona pellucida thickness did not change between ovulationand 16–20 h after fertilization. Zona pellucida thicknesswas not related to ooplasm diameter. In conclusion, zona pellucidathickness appears to be an additional factor that should betaken into account when interpreting the fertilization rate.Zona pellucida thickness influences sperm penetration, evenwhen the spermatozoa are considered normal. From a clinicalpoint of view, a thick zona pellucida (22 µm) could bean indicator for the use of micro-injection procedures.     

Does disclosure of emotions facilitate recovery from bereavement? Evidence from two prospective studies

Two longitudinal studies assessed whether disclosure of emotions facilitates recovery from bereavement. Study 1 tested prospectively over a 2-year period whether the extent to which bereaved persons talked about their loss to others and disclosed their emotions was associated with better adjustment to the loss of a marital partner. There was no evidence that disclosure facilitated adjustment. Study 2 randomly assigned recently bereaved individuals either to the Pennebaker writing task (J. W. Pennebaker & S. K. Beall, 1986) or to no-essay control conditions. The writing task did not result in a reduction of distress or of doctors visits either immediately after the bereavement or at a 6-month follow-up. Beneficial effects were not demonstrated for bereaved persons who had suffered an unexpected loss or who at the time of the study still expressed a high need for emotional disclosure.     

Does the semantic activation of quantity representations influence motor parameters?

In size and parity judgment tasks, we investigated whether the activation of numerical quantity exerts an influence on motor response parameters such as response force. Results showed typically strong effects on reaction time of numerical distance in the size judgment task (Experiments 1 and 2) and SNARC-compatibility (Experiment 1) in both tasks, indicating that semantic quantity representations were activated. Response force, however, varied at most weakly with the numerical magnitudes of the digits. Our results place limits on previously suggested interconnections of the magnitude and response systems. Activations within the magnitude system seem to have a strong influence on the initiation and selection of which action to produce, but only a little influence on the dynamics of response production (i.e., response execution).

Does the microenvironment influence the cell types of origin for prostate cancer?

Despite several recent studies addressing the cells of origin for prostate cancer, there is still considerable discussion in the field regarding the most relevant target populations for transformation. Tissue regeneration studies have pointed to a basal cell origin for mouse and human prostate cancer. In contrast, genetically engineered mouse models demonstrate that cells within both the basal and luminal layers can initiate murine prostate cancer. Based on differences between these two approaches, we propose that further work should address the requirement for microenvironmental components such as immune or mesenchymal cells on epithelial cell types of origin for prostate cancer.