Human Reproduction--the next phase in its development.
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Humans↗
Biomedical subjects
David H Barlow
Publications and source records attributed to David H Barlow.
Rater bias in a blinded randomized placebo-controlled psychiatry trial.
Rater bias occurs when rater knowledge of treatment assignment modifies the outcome assessment. Raters may be unconsciously influenced by inclinations for or against a particular treatment and consequently may give a more or less generous assessment depending upon these biases. Blinding of raters by keeping raters unaware of treatment assignment is one way to limit bias influencing assessment due to knowledge of treatment assignment. Unblinding may be particularly problematic in efficacy studies comparing placebo to drugs and/or non-drug psychotherapy treatments where subjects may reveal drug side-effects or mention their therapist by name, thus unblinding their treatment assignment. We present a new instrumental variable statistical approach for assessing the association between success in blinding and its impact on efficacy estimates of active drug and/or cognitive behavioural psychotherapy versus placebo in the multicentre comparative treatment study of panic disorder. Despite the uncertainty involved in assessing bias that may be unobserved and unconscious, we will show how to derive a bound for the impact of rater bias.
Bias↗
Mosaicism for mitochondrial DNA polymorphic variants in placenta has implications for the feasibility of prenatal diagnosis in mtDNA diseases.
Women who have had a child with mitochondrial DNA (mtDNA) disease need to know the risk of recurrence, but this risk is difficult to estimate because mutant and wild-type (normal) mtDNA coexist in the same person (heteroplasmy). The possibility that a single sample may not reflect the whole organism both impedes prenatal diagnosis of most mtDNA diseases, and suggests radical alternative strategies such as nuclear transfer. We used naturally occurring mtDNA variants to investigate mtDNA segregation in placenta. Using large samples of control placenta, we demonstrated that the level of polymorphic heteroplasmic mtDNA variants is very similar in mother, cord blood and placenta. However, where placental samples were very small (< 10 mg) there was clear evidence of variation in the distribution of mtDNA polymorphic variants. We present the first evidence for variation in mutant load, that is, mosaicism for mtDNA polymorphic variants in placenta. This suggests that mtDNA mutants may segregate in placenta and that a single chorionic villous sample (CVS) may be unrepresentative of the whole placenta. Duplicates may be necessary where CVS are small. However, the close correlation of mutant load in maternal, fetal blood and placental mtDNA suggests that the average load in placenta does reflect the load of mutant mtDNA in the baby. Provided that segregation of neutral and pathogenic mtDNA mutants is similar in utero, our results are generally encouraging for developing prenatal diagnosis for mtDNA diseases. Identifying mtDNA segregation in human placenta suggests studies of relevance to placental evolution and to developmental biology.
Chorionic Villi Sampling↗
Tinnitus among Cambodian refugees: relationship to PTSD severity.
Consecutive Cambodian refugees attending a psychiatric clinic were assessed for the presence and severity of current tinnitus (i.e., at least one episode in the last month). Fifty percent (52/104) of surveyed patients had tinnitus. Among the tinnitus patients, posttraumatic stress disorder (PTSD) rates were significantly more elevated than among nontinnitus patients (OR=13.5; 95% CI=5.8 to 39.4), as were Clinician-Administered PTSD Scale (CAPS) scores. In a hierarchical regression among tinnitus patients (n=52), tinnitus-related trauma associations and catastrophic cognitions accounted for variability in CAPS severity beyond a measure of tinnitus severity. Among tinnitus patients, tinnitus-related trauma associations and catastrophic cognitions mediated the effect of tinnitus severity on CAPS severity.
Cambodia↗
Avoidance behavior in panic disorder: the moderating influence of perceived control.
The relations among anxiety sensitivity, perceived control, and agoraphobia were examined in 239 patients diagnosed with panic disorder (PD). Most patients exhibited agoraphobia accompanying their PD (98% situational avoidance; 90% experiential avoidance; and 80% endorsed interoceptive fear and avoidance). Anxiety sensitivity and perceived emotional control were associated with agoraphobia, and perceived threat control was found to moderate the relationship between anxiety sensitivity and agoraphobia. Lower levels of perceived control were associated with a stronger relationship between anxiety sensitivity and agoraphobia. Results were consistent for self-reported and clinician-rated agoraphobia. Implications for the role of perceived control in agoraphobia development and treatment are discussed.
Adolescent↗
Acceptability and suppression of negative emotion in anxiety and mood disorders.
The present study investigated perceived acceptability and suppression of negative emotion in participants with anxiety and mood disorders. Sixty participants with these disorders and 30 control participants watched an emotion-provoking film and completed self-report measures of their experience and regulation of emotions. The film elicited similar increases in negative emotion for clinical and nonclinical participants; however, clinical participants judged their resulting emotions as less acceptable and suppressed their emotions to a greater extent. The higher level of suppression in the clinical group was attributable to females in the clinical group suppressing their emotions more than females in the nonclinical group. For all participants, high levels of suppression were associated with increased negative emotion during the film and during a postfilm recovery period. Further analyses showed that appraising emotions as unacceptable mediated the relationship between negative emotion intensity and use of suppression in the clinical group. This study extends the literature on emotion regulation to a clinical sample and suggests that judging emotions as unacceptable and suppressing emotions may be important aspects of the phenomenology of emotional disorders.
Adolescent↗
Pregnancy outcome among twins conceived after subfertility treatment compared with natural twins: A population-based study.
Pregnancy outcome and characteristics of women who conceive following subfertility treatment remains a subject of great interest. We analyzed these variables among 199 women who delivered a registerable twin birth compared with 1773 women who delivered a naturally conceived twin birth in a population-based obstetric cohort drawn from around Oxford, England. Treatment was restricted to conceptions involving simple ovulation induction only. Treated mothers were of significantly higher social class and older, more likely to deliver girls and to be delivered by cesarean section, and significantly less likely to be smokers at the time of antenatal booking and to have delivered previous pregnancies. Pregnancy outcome was similar between the two groups for most measures, with the exception of birthweight which was lower in treated twins, though not significantly so. Overall the results are reassuring with respect to outcome in twin pregnancies following simple ovulation induction.
Adult↗
Differential expression of alternatively spliced transcripts of HLA-G in human preimplantation embryos and inner cell masses.
It has been reported that preimplantation human embryos secrete HLA-G, and the levels may be predictive of their ability to implant. However, it is not known which of the membrane-bound (HLA-G 1-4) and soluble (HLA-G 5-6) alternatively spliced forms are present, nor the developmental stage at which they appear. Therefore, we have investigated HLA-G mRNA isoform expression on single embryos at the two-, four-, six-, and eight-cell, morula, and blastocyst stages. The percentage of embryos expressing each HLA-G isoform mRNA increased with developmental stage, but contrary to expectation, HLA-G5 mRNA was not detected in single two- to eight-cell embryos and was only expressed by 20% of morulae and blastocysts. Similarly, soluble HLA-G6 mRNA was not detected until the blastocyst stage and then in only one-third of embryos. In contrast, labeling with MEM G/9 Ab (specific for HLA-G1 and -G5) was observed in 15 of 20 two- to eight-cell embryos and 5 of 5 blastocysts. This disparity between mRNA and protein may be due to HLA-G protein remaining from maternal oocyte stores produced before embryonic genome activation and brings into question the measurement of soluble HLA-G for clinical evaluation of embryo quality. Although HLA-G is expressed in the preimplantation embryo, later it is primarily expressed in the invasive trophoblast of the placenta rather than the fetus. Therefore, we have investigated whether down-regulation of HLA-G first occurs in the inner cell mass (precursor fetal cells) of the blastocyst and, in support of this concept, have shown the absence HLA-G1 and -G5 protein and mRNA.
Alternative Splicing↗
Effects of suppression and acceptance on emotional responses of individuals with anxiety and mood disorders.
The present investigation compared the subjective and physiological effects of emotional suppression and acceptance in a sample of individuals with anxiety and mood disorders. Sixty participants diagnosed with anxiety and mood disorders were randomly assigned to one of two groups. One group listened to a rationale for suppressing emotions, and the other group listened to a rationale for accepting emotions. Participants then watched an emotion-provoking film and applied the instructions. Subjective distress, heart rate, skin conductance level, and respiratory sinus arrhythmia were measured before, during, and after the film. Although both groups reported similar levels of subjective distress during the film, the acceptance group displayed less negative affect during the post-film recovery period. Furthermore, the suppression group showed increased heart rate and the acceptance group decreased heart rate in response to the film. There were no differences between the two groups in skin conductance or respiratory sinus arrhythmia. These findings are discussed in the context of the existing body of research on emotion regulation and current treatment approaches for anxiety and mood disorders.
Adolescent↗
Genomewide linkage study in 1,176 affected sister pair families identifies a significant susceptibility locus for endometriosis on chromosome 10q26.
Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometrium in sites outside the uterus. Its cause remains uncertain despite >50 years of hypothesis-driven research, and thus the therapeutic options are limited. Disease predisposition is inherited as a complex genetic trait, which provides an alternative route to understanding the disease. We seek to identify susceptibility loci, using a positional-cloning approach that starts with linkage analysis to identify genomic regions likely to harbor these genes. We conducted a linkage study of 1,176 families (931 from an Australian group and 245 from a U.K. group), each with at least two members--mainly affected sister pairs--with surgically diagnosed disease. We have identified a region of significant linkage on chromosome 10q26 (maximum LOD score [MLS] of 3.09; genomewide P = .047) and another region of suggestive linkage on chromosome 20p13 (MLS = 2.09). Minor peaks (with MLS > 1.0) were found on chromosomes 2, 6, 7, 8, 12, 14, 15, and 17. This is the first report of linkage to a major locus for endometriosis. The findings will facilitate discovery of novel positional genetic variants that influence the risk of developing this debilitating disease. Greater understanding of the aberrant cellular and molecular mechanisms involved in the etiology and pathophysiology of endometriosis should lead to better diagnostic methods and targeted treatments.
Australia↗
Menopause and HRT--the state of the art in Europe.
The HRT field has been dramatically affected by the publication on major randomised controlled trials of the long-term effects of HRT. The publicity surrounding the publication of these data has affected public and regulatory perceptions of HRT and its role in healthcare, including the relatively short-term use of HRT for the relief of menopausal symptoms. An evidence-based appraisal of the role of HRT today is best achieved by considering the different components of the effects of HRT individually, based on the best trial evidence, and then considering these together in the context of the age of woman concerned and the specific components relevant to that woman's health profile. This paper summarises the effects of HRT using this approach in the context of European practice today and describes the events surrounding the regulatory and scientific society position statements.
Alzheimer Disease↗
A psychometric reanalysis of the Albany Panic and Phobia Questionnaire.
The psychometric properties of the 27-item Albany Panic and Phobia Questionnaire (APPQ) were evaluated in 1930 outpatients with DSM-IV anxiety and mood disorders. Although prior findings of a 3-factor latent structure were upheld in several replications (Social Phobia, Agoraphobia, Interoceptive), three items failed to load on their predicted factor (Interoceptive). Multiple-groups CFAs indicated that the measurement properties of the APPQ were invariant in male and female patients, with the exception of an intercept of one item from the Agoraphobia scale which evidenced bias against females. The three APPQ dimensions were consistently associated with high levels of scale reliability and factor determinacy. Strong evidence of concurrent validity of the Social Phobia and Agoraphobia factors was obtained in relation to interview and questionnaire measures. Although the Interoceptive factor was more strongly related to criterion measures of anxiety sensitivity and fear of panic than Social Phobia, the Agoraphobia factor had the strongest relationships with these validity indices. The results are discussed in regard to psychometric implications for the APPQ and conceptual issues pertaining to the discriminant validity of fear of agoraphobic situations and fear of sensation-producing activities.
Adolescent↗
Introduction to the special section: toward a dimensionally based taxonomy of psychopathology.
Much current psychopathology research is framed by categorical constructs. Limitations of categorical constructs have been articulated, and dimensional constructs are often proposed as viable alternatives to categories of psychopathology. The purpose of this Special Section is to articulate and discuss diverse issues that arise in contemplating dimensional constructs as targets for psychopathology research.
Diagnostic and Statistical Manual of Mental Disord↗
Dimensional versus categorical classification of mental disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders and beyond: comment on the special section.
The value of including dimensional elements in the Diagnostic and Statistical Manual of Mental Disorders (DSM) has been recognized for decades. Nevertheless, no proposals have been made for introducing dimensional classification in the diagnostic system in a valid and feasible manner. As an initial step in this endeavor, the authors suggest introducing dimensional severity ratings to the extant diagnostic categories and criteria sets. Although not without difficulties, this would begin to determine the feasibility of dimensional classification and would address some limitations of the purely categorical approach (e.g., failure to capture individual differences in disorder severity, and clinically significant features subsumed by other disorders or falling below conventional DSM thresholds). The utility of incorporating broader dimensions of temperament and personality in diagnostic systems beyond the fifth edition of the DSM is also discussed.
Diagnostic and Statistical Manual of Mental Disord↗
Physical, mental, and social catastrophic cognitions as prognostic factors in cognitive-behavioral and pharmacological treatments for panic disorder.
The authors explored the prognostic value of 3 different types of catastrophic cognitions in the treatment of panic disorder with and without mild-to-moderate agoraphobia using a sample of 143 participants who received either cognitive-behavioral therapy (CBT) or imipramine in a randomized controlled trial. Stronger fears of social catastrophes both prior to and following treatment with CBT or imipramine were associated with a poorer outcome. In contrast, cognitions involving physical or mental catastrophes were unrelated to outcome, regardless of whether these thoughts were measured prior to or following treatment. These findings are consistent with the notion that although the intensity of physical catastrophe cognitions may best discriminate between panic disorder and other anxiety disorders, it is the intensity of social catastrophe cognitions that is most closely tied to success in treating this disorder.
Adult↗
Effects of transdermal nicotine during imaginal exposure to anxiety and smoking cues in college smokers.
In a 2 (patch) x 2 (smoking) x 2 (anxiety) mixed design, 52 undergraduate smokers randomly received a nicotine (21 mg) or placebo patch. After a 4-hr nicotine absorption/deprivation period, participants imagined several scenarios varying in cue content: (a) anxiety plus smoking, (b) anxiety, (c) smoking, and (d) neutral. Although smoking urge increased in both the nicotine and placebo conditions after the absorption/deprivation period, those who received the placebo reported significantly greater urge. During the cue reactivity trials, a significant Patch x Smoking x Anxiety interaction effect was observed for urge. However, participants who received nicotine still experienced moderate urges, indicating that nicotine did not attenuate cue-elicited urge. Transdermal nicotine did not diminish anxiety during the absorption/deprivation period or in response to the cues.
Administration, Cutaneous↗
What's new about evidence-based assessment?
A clear consensus has emerged around the world concerning the desirability and even the urgency of basing health care delivery systems on evidence. Among behavioral health care providers such as psychologists, evidence-based practice (EBP) has been focused largely on interventions. Psychologists have long emphasized a scientifically based psychometric approach to the development of assessment procedures. Nevertheless, the era of evidence-based assessment highlights 2 somewhat different issues. First, sophisticated assessment is closely integrated with our emerging conceptions of psychopathology, rather than standing separate from these conceptions. Second, broad-based ongoing outcomes assessment systems are increasingly required for EBP on the part of governments and health care policymakers. This article summarizes these developments and looks to the future.
Evidence-Based Medicine↗
The debate on single embryo transfer in IVF. How will today's arguments be viewed from the perspective of 2020?
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Embryo Transfer↗