Morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic and fetal growth: the Rotterdam Periconception Cohort.

STUDY QUESTION: Is morphologic development of the first-trimester utero-placental vasculature associated with embryonic growth and development, fetal growth, and birth weight percentiles? SUMMARY ANSWER: Using the utero-placental vascular skeleton (uPVS) as a new imaging marker, this study reveals morphologic development of the first-trimester utero-placental vasculature is positively associated with embryonic growth and development, fetal growth, and birth weight percentiles. WHAT IS KNOWN ALREADY: First-trimester development of the utero-placental vasculature is associated with placental function, which subsequently impacts embryonic and fetal ability to reach their full growth potential. The attribution of morphologic variations in the utero-placental vascular development, including the vascular structure and branching density, on prenatal growth remains unknown. STUDY DESIGN, SIZE, DURATION: This study was conducted in the VIRTUAL Placental study, a subcohort of 214 ongoing pregnancies, embedded in the prospective observational Rotterdam Periconception Cohort (Predict study). Women were included before 10 weeks gestational age (GA) at a tertiary referral hospital in The Netherlands between January 2017 and March 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained three-dimensional power Doppler volumes of the gestational sac including the embryo and the placenta at 7, 9, and 11 weeks of gestation. Virtual Reality-based segmentation and a recently developed skeletonization algorithm were applied to the power Doppler volumes to generate the uPVS and to measure utero-placental vascular volume (uPVV). Absolute vascular morphology was quantified by assigning a morphologic characteristic to each voxel in the uPVS (i.e. end-, bifurcation-crossing-, or vessel point). Additionally, total vascular length (mm) was calculated. The ratios of the uPVS characteristics to the uPVV were calculated to determine the density of vascular branching. Embryonic growth was estimated by crown-rump length and embryonic volume. Embryonic development was estimated by Carnegie stages. Fetal growth was measured by estimated fetal weight in the second and third trimester and birth weight percentiles. Linear mixed models were used to estimate trajectories of longitudinal measurements. Linear regression analysis with adjustments for confounders was used to evaluate associations between trajectories of the uPVS and prenatal growth. Groups were stratified for conception method (natural/IVF-ICSI conceptions), fetal sex (male/female), and the occurrence of placenta-related complications (yes/no). MAIN RESULTS AND THE ROLE OF CHANCE: Increased absolute vascular morphologic development, estimated by positive random intercepts of the uPVS characteristics, is associated with increased embryonic growth, reflected by crown-rump length (endpoints ß = 0.017, 95% CI [0.009; 0.025], bifurcation points ß = 0.012, 95% CI [0.006; 0.018], crossing points ß = 0.017, 95% CI [0.008; 0.025], vessel points ß = 0.01, 95% CI [0.002; 0.008], and total vascular length ß = 0.007, 95% CI [0.003; 0.010], and similarly with embryonic volume and Carnegie stage, all P-values ≤ 0.01. Density of vascular branching was negatively associated with estimated fetal weight in the third trimester (endpoints: uPVV ß = -94.972, 95% CI [-185.245; -3.698], bifurcation points: uPVV ß = -192.601 95% CI [-360.532; -24.670]) and birth weight percentiles (endpoints: uPVV ß = -20.727, 95% CI [-32.771; -8.683], bifurcation points: uPVV ß -51.097 95% CI [-72.257; -29.937], and crossing points: uPVV ß = -48.604 95% CI [-74.246; -22.961])), all P-values < 0.05. After stratification, the associations were observed in natural conceptions specifically. LIMITATION, REASONS FOR CAUTION: Although the results of this prospective observational study clearly demonstrate associations between first-trimester utero-placental vascular morphologic development and prenatal growth, further research is required before we can draw firm conclusions about a causal relationship. WIDER IMPLICATIONS OF THE FINDINGS: Our findings support the hypothesis that morphologic variations in utero-placental vascular development play a role in the vascular mechanisms involved in embryonic and fetal growth and development. Application of the uPVS could benefit our understanding of the pathophysiology underlying placenta-related complications. Future research should focus on the clinical applicability of the uPVS as an imaging marker for the early detection of fetal growth restriction. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Department of Obstetrics and Gynecology of the Erasmus MC, University Medical Centre, Rotterdam, The Netherlands. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: Registered at the Dutch Trial Register (NTR6854).

Ultrafast Transition from State-Blocking Dynamics to Electron Localization in Transition Metal ß-Tungsten.

We describe an ultrafast transition of the electronic response of optically excited transition metal ß-tungsten with few-femtosecond time resolution. The response moves from a regime where state filling of the excited carrier population around the Fermi level dominates towards localization of carriers onto the outer d orbitals. This is in contrast to previous measurements using ultrafast element-specific core-level spectroscopy enabled by attosecond transient absorption spectroscopy on transition metals such as titanium and around the transition metal atom in transition metal dichalchogenides MoTe_{2} and MoSe_{2}. This surprisingly different dynamical response for ß-tungsten can be explained by considering the electron-electron dynamics on a few-femtosecond timescale and the slower electron-phonon thermalization dynamics.

First-trimester utero-placental (vascular) development and embryonic and fetal growth: The Rotterdam periconception cohort.

INTRODUCTION: Impaired placental development is a major cause of fetal growth restriction (FGR) and early detection will therefore improve antenatal care and birth outcomes. Here we aim to investigate serial first-trimester ultrasound markers of utero-placental (vascular) development in association with embryonic and fetal growth. METHODS: In a prospective cohort, we periconceptionally included 214 pregnant women. Three-dimensional power Doppler ultrasonography at 7, 9 and 11 weeks gestational age (GA) was used to measure placental volumes (PV) and basal plate surface area by Virtual Organ Computer-aided AnaLysis™, and utero-placental vascular volume (uPVV), crown-rump length (CRL) and embryonic volume (EV) by a V-scope volume rendering application. Estimated fetal weight (EFW) was measured by ultrasound at 22 and 32 weeks GA and birth weight percentile (BW) was recorded. Linear mixed models and regression analyses were applied and appropriately adjusted. All analyses were stratified for fetal sex. RESULTS: PV trajectories were positively associated with CRL (ßadj = 0.416, 95%CI:0.255; 0.576, p < 0.001), EV (ßadj = 0.220, 95%CI:0.058; 0.381, p = 0.008) and EFW (ßadj = 0.182, 95%CI:0.012; 0.352, p = 0.037). uPVV trajectories were positively associated with CRL (ßadj = 0.203, 95%CI 0.021; 0.384, p = 0.029). In girls, PV trajectories were positively associated with CRL (p < 0.001), EV (p = 0.018), EFW (p = 0.026), and uPVV trajectories were positively associated with BW (p = 0.040). In boys, positive associations were shown between PV trajectories and CRL (p = 0.002), and between uPVV trajectories and CRL (p = 0.046). DISCUSSION: First-trimester utero-placental (vascular) development is associated with embryonic and fetal growth, with fetal sex specific modifications. This underlines the opportunity to monitor first-trimester placental development and supports the associations with embryonic and fetal growth.

Management of rifampicin-resistant TB: programme indicators and care cascade analysis in South Africa.

BACKGROUND: Xpert® MTB/RIF was expected to revolutionise the management of rifampicin-resistant TB (RR-TB) by enabling rapid and decentralised diagnosis of rifampicin (RIF) resistance.METHODS: We performed a care cascade analysis for a cohort of RR-TB patients managed under programmatic conditions. Cumulative incidences of time to completion of the RR-TB care cascade steps were estimated, reasons for delay or attrition from the cascade investigated and WHO programme indicators for monitoring of RR-TB programmes calculated.RESULTS: Of 502 patients diagnosed with RR-TB using Xpert, 64% initiated multidrug-resistant TB (MDR-TB) treatment immediately, 20% after some first-line treatment, 16% never initiated MDR-TB treatment, mainly because of death (44%) or loss to follow-up (26%) soon after diagnosis. A supplementary sputum sample was collected within 14 days of treatment in 58.8% of cases. Only 63% of RR-TB cases were assessed for isoniazid resistance, and only 65% of MDR-TB cases were evaluated for pre-XDR-TB (extensively drug-resistant TB). Treatment was individualised in 57% of pre-XDR and 68% of XDR-TB patients. Only 8% completed the entire RR-TB care cascade as intended.CONCLUSION: Fidelity to the RR-TB algorithm was poor, with substantial losses at each step of the cascade, highlighting the fact that implementation of novel technologies needs to be accompanied by health system strengthening to maximise impact.

Whole-genome sequencing for TB source investigations: principles of ethical precision public health.

BACKGROUND: Whole-genome sequencing (WGS) of Mycobacterium tuberculosis allows rapid, accurate inferences about the sources, location and timing of transmission. However, in an era of heightened concern for personal privacy and science distrust, such inferences could result in unintended harm and undermine the public´s trust.METHODS: We held interdisciplinary stakeholder discussions and performed ethical analyses of real-world illustrative cases to identify principles that optimise benefit and mitigate harm of M. tuberculosis WGS-driven TB source investigations.RESULTS: The speed and precision with which real-time WGS can be used to associate M. tuberculosis strains with sensitive information has raised important concerns. While detailed understanding of transmission events could mitigate harm to vulnerable patients and communities when otherwise unfairly blamed for TB outbreaks, the precision of WGS can also identify transmission events resulting in social blame, fear, discrimination, individual or location stigma, and the use of defaming language by the public, politicians and scientists. Public health programmes should balance the need to safeguard privacy with public health goals, transparency and individual rights, including the right to know who infects whom or where.CONCLUSIONS: Ethical challenges raised by real-time WGS-driven TB source investigation requires public health authorities to move beyond their current legal mandate and embrace transparency, privacy and community engagement.

Validation of the Oral Survey-B System for Electronic Data Capture in National Oral Health Surveys.

The aims of the present study were to incorporate and to validate the electronic capture of participant-related outcomes into the Oral Survey-B System, which was originally developed for the electronic capture of clinical data. The validation process compared the performances of electronic and handwritten data captures. The hypothesis of noninferiority would be established if participants performed electronic data capture of the questionnaire survey with an effectiveness of at least 95% of that of handwritten data capture. In this multicenter, randomized, one-period crossover study design, participants (n = 261) were allocated to start with either electronic or handwritten data capture. The incorporation of the electronic self-completed questionnaire into the Oral Survey-B System was successful. The validation of the electronic questionnaire was performed by participants aged from 18 to 75 years. The interrater reliability of participants performing electronic and handwritten data capture of nonclinical assessments per questionnaire and per entry showed a kappa value of 0.72 (95% CI: 0.53-0.94). The noninferiority of electronic data capture in relation to that of the handwritten data capture and transfer was shown (p < 0.0001; 95% CI: 1.47-2.99). In conclusion, the electronic capture of participant-related outcomes with the Oral Survey-B System, originally designed for capture of clinical data, was validated. The electronic data capture was accurate and limited the number of errors. The participants were able to perform electronic data capture effectively, supporting its implementation in further National Oral Health Surveys. With the consideration of participant preference and time savings, this could lead to the implementation of electronic data capture worldwide in National Oral Health Surveys.

[Increasing use of social benefits by young people with chronic illness or disability in the Netherlands]. / Zunahme der Inanspruchnahme von Sozialleistungen bei jungen Personen mit einer chronischen Erkrankung bzw. Behinderung in den Niederlanden.

Young handicapped citizens in the Netherlands have increasingly been receiving social benefits or special services during the last five years. Dutch governmental departments have therefore commissioned an applied social policy research. We analyzed six benefits (for example special education, psychological healthcare, and Wajong benefits for young disabled). The usage of all these provisions is increasing. In particular we focus on "Wajong" (a sort of pension for Dutch young disabled people) and its social consequences. The number of Wajong benefits is growing strongly. In 2006 every 22nd person aged 18 (4.5%) claimed and received this disability benefit. Also, the statistical trend is that people with a handicap are less often employed and are more often unemployed. So there is an ongoing political discussion about these provisions with special attention to Wajong.

Barriers to physician identification and treatment of family violence: lessons from five communities.

Since the Surgeon General's Workshop on Violence and Public Health (Leesburg, Virginia, October 27-29, 1985), a substantial literature has developed about the limitations of the health care response to family violence. Many contributions have reflected experiences in limited numbers of practice settings (e.g., a single emergency department or hospital). Until 1990, however, there had been no community-based studies. The Robert Wood Johnson Foundation asked a multidisciplinary team from Education Development Center, Inc. and Children's Hospital (Boston) to investigate the health care responses to family violence in five diverse communities. This qualitative study, comprising more than 480 interviews, provided a vivid picture of the barriers facing physicians and other health care providers in identifying, treating, and referring victims of family violence. It also illuminated the relations of the health care systems in these communities with other key sectors, including agencies and the judiciary. The key findings from the five-city study remain relevant because (1) it is the only large-scale, multi-community-based assessment of the barriers facing physicians; (2) it identified, or in some cases confirmed, both institutional and educational barriers limiting the effectiveness of even the most committed physicians; (3) it identified, or in some cases confirmed, specific areas of knowledge, attitudes, and skills development that should be incorporated in medical education; and (4) its conclusions continue to be reflected in subsequent contributions to the literature. In each of these ways, therefore, it informs the other articles in this supplement.

PIP: An exploratory study, initiated in 1990 by the Robert Wood Johnson Foundation in 5 US cities (Atlanta, Georgia; Duluth, Minnesota; Providence, Rhode Island; Riverside, California; and Roswell, New Mexico), identified numerous barriers to an effective response by the health care system to family violence. Over the course of 2 visits to each site, 484 health professionals and community activists were interviewed. Although respondents in all 5 communities agreed that family violence was having a serious impact on the lives and health of women, children, and the elderly, none of the health systems addressed family violence comprehensively in terms of programs, policies, or clinical practice norms. Physicians, nurses, and other health care professionals who worked with victims of family violence reported they were marginalized by their colleagues and identified economic, social, and psychological disincentives to work in this area. The health care system's ability to respond to family violence was significantly impeded by providers' prejudices (e.g., class elitism, racism, sexism, ageism, homophobia) toward both the victims and perpetrators of violence. Overburdened public facilities, the unwillingness of private facilities to serve this clientele, low Medicaid participation rates, underinsured or uninsured status, and poor public transportation further restricted victims' access to services. Service provision was most lacking for victims of elder abuse. Finally, there was a lack of effective coordination among agencies responsible for addressing family violence.

Evaluation of a hospital-based youth violence intervention.

To decrease adolescent morbidity and mortality and improve the quality of life, a violence-prevention consultation is offered to hospitalized victims of nondomestic violence. The context is a violence-prevention team approach to patient assessment, treatment, and follow-up. Psychoeducational counseling emphasizes the individual through a cognitive behavioral approach and also recognizes the individual in the proximal social setting through referrals to community resources. The in-hospital component draws on the health beliefs model, self-efficacy, the theory of reasoned action and their synergy with cognitive mediation theory as expressed in developmental psychology. The target group for the intervention is adolescents (12-17 years of age) who have been victims of violent assaults severe enough to warrant treatment at a Level One trauma center. The six steps in the intervention are to (1) review and assess the incident, (2) review the patient's conflict-resolution strategies and introduce nonviolent alternatives, (3) provide information on the prevalence of violence/homicide and determine the patient's risk status, (4) explore the patient's coping skills and support system, (5) develop a plan to stay safe, and (6) refer patient to services for follow-up activities. Approximately 15 study participants are identified each month, half of whom are randomly assigned to receive the intervention. Over the 12-month recruitment interval, approximately 180 adolescent patients will be identified. Baseline data are collected through hospital intake procedures and chart reviews. A battery of standardized measures supplemented by a brief structured, closed-ended interview is collected four months after the youths leave the hospital. Preliminary baseline data for 39 youths are reported. The "typical" youth is a 16-year-old African-American male. Even though nearly one third of victims had been shot, the typical patient was injured in a fight during which he was kicked, bitten, or beaten with or without a blunt instrument. The majority of incidents involved only one attacker who was known to the victim. Nearly half the injuries were precipitated by an argument or fight. No statistically significant differences between intervention subjects and nonintervention controls in terms of baseline variables have been observed. For inner-city adolescent victims of violent assaults, a hospital-based intervention offers a unique opportunity for reduction of the incidence of reinjury. We describe the elements of the intervention, including the theoretical basis and implementation; detail the overall evaluation design including modifications; and present preliminary analyses of baseline data.

Criminal justice outcomes of prosecution of child sexual abuse: a case flow analysis.

This study examined the progress and disposition of child sexual abuse cases referred for prosecution in four urban jurisdictions. Most cases were accepted for prosecution. The vast majority of cases carried forward for prosecution resulted in guilty pleas. Only 9% of the total sample went to trial. A majority of the small number that went to trial were convicted. Over 3/4 of those convicted were incarcerated. The rate at which cases were carried forward for prosecution and convicted was comparable to that of a national sample of felony arrests overall, but child sexual abuse cases were more likely to go to trial (p < .005) and received more severe sentences (p < .005). Our results are strikingly consistent with those from previous studies of prosecution of child sexual abuse. A new understanding of prosecution of child sexual abuse is recommended that takes into account the large proportion of cases that do not go to trial.

Prosecution of child sexual abuse: which cases are accepted?

This study examined the relationship of case characteristics, maternal support, and child psychopathology to acceptance of child sexual abuse cases for prosecution. Cases referred to prosecutors' offices over a 1-year period in four urban jurisdictions (N = 431) were examined, and a smaller sample of mothers and children (N = 289) were interviewed as well. Background characteristics of the perpetrator and victim, severity of abuse, and nature of available evidence were all significantly related to acceptance for prosecution. Specific independent predictors of acceptance were victim age, presence of oral-genital abuse, use or threat of force, duration of abuse, and presence of physical or eyewitness evidence. With other variables controlled, maternal support was higher and child internalizing psychopathology lower in accepted cases. The results are interpreted in terms of prosecutors' concern for serving justice and protecting children and their perceptions of their ability to prosecute cases successfully.

The Intervention Stressors Inventory: a measure of the stress of intervention for sexually abused children.

This paper describes the development and initial validation of the Intervention Stressors Inventory (ISI), a new scale designed to measure the level of stress sexually abused children experience as a result of societal intervention. Estimates of the relative stress level of various interventions were obtained from 98 professionals; a police interview was the designated anchor with a score of 50 points. Resulting scores from the survey included 35 points for social worker interview, 100 points for placement in foster care, and 111 points for testimony in criminal court. Factors that could potentially modify the stress of any given event were also considered. Interviews with 254 sexually abused children and their parents, 9 months after their cases were reported, provided an opportunity to examine the validity of the instrument. Weighted scores for each child were generated based on their experiences. Validity was supported by higher scores for older children, varying patterns of scores in different jurisdictions and a decline in scores over the one-year period in which jurisdictions were actively seeking to reduce the intrusiveness of intervention. Early results suggest that the ISI is useful as a research tool and as a guide in our efforts to reduce the trauma of intervention.

Molecular cytogenetic analysis of a familial pericentric inversion of chromosome 12.

We describe the application of multi-color fluorescence in situ hybridization (FISH) in the characterization of a familial pericentric inversion. Using chromosome 12 short- and long-arm specific DNA probes, fast and reliable discrimination between normal and inversion chromosome 12 or recombinant inversion chromosome 12 was possible. FISH thus provides a reliable means for prenatal detection of balanced or unbalanced chromosome 12 rearrangements in this family. This approach is possible for identification of similar chromosome rearrangements provided that probes for the putatively involved chromosome region are available.

Asymmetric action in the human newborn: sex differences in patterns of organization.

We developed a procedure and scale to quantify movement asymmetry in 36 full-term newborns from several normal newborn nurseries (Measure of Behavioral Laterality, MOBL). The majority of newborns had elicited reflexes and spontaneous movements that were stronger and more coordinated on the right than on the left side of the body; there was no asymmetry in the latency, threshold, or habituation of these behaviors. Although asymmetry of different movements was associated if they relied on the same motor pool, there was little association of movement asymmetries among different body regions, indicating that multiple subsystems, rather than a single asymmetric system, controls asymmetric action in the newborn. Finally, there was a sex difference in asymmetry of all 3 distal lower-body elicited reflexes: females were right biased, but the majority of males were left biased. These sex differences are discussed in terms of alternative mechanisms for the development of asymmetric action and the role of newborn reflexes in adult voluntary movement.

Victimization of mothers of abused children: a controlled study.

To search for indicators of violence against mothers of child abuse victims by husbands or boyfriends, the women's medical records were reviewed and compared to records of mothers of a nontraumatized child comparison group. Of the 32 children ascertained in a 6-month interval, the records of mothers of 19 (59.4%) were diagnostic or highly suggestive of current or previous victimization. Although the prevalence of documented violence against the mothers of children in the comparison group was an unexpectedly high 16%, the case-control difference was highly significant (P less than .001). Although differences were found in the (younger) ages and (higher) parity of mothers of abused children, these differences did not predict risk of mothers' exposures to violence in a multivariate analysis. The rate of violence against single mothers of child abuse victims, however, was four times the rate against mothers who were married (P = .022). These findings suggest a need to broaden the diagnostic conceptualization of child abuse to include maternal victimization and argue for including data concerning maternal risk in formulating diagnoses and disposition plans for abused children.

Abuse and victimization: a life-span developmental perspective.

A conceptualization of coping and adaptation following victimization is presented from a life-span developmental perspective. Recovery is characterized as an evolving process of interaction among three dimensions: social cognition, environmental sensitivity, and emotional-behavioral functioning. The model is illustrated through an individual case study and through an approach to research on outcomes of sexual victimization.

What residents know about child abuse. Implications of a survey of knowledge and attitudes.

Residency training programs are the appropriate milieu in which physicians should receive specialized training in the diagnosis and management of child abuse. The purposes of the present study were to assess and compare residents' knowledge of child abuse and their attitudes toward the propriety of different forms of childhood discipline. We surveyed 192 residents from seven different training programs with questionnaires probing their knowledge of child abuse and their attitudes toward childhood disciplinary measures; 161 (84%) of the questionnaires were satisfactorily completed by residents in pediatrics (n = 87), family medicine (n = 51), and surgery (n = 23). Both pediatric residents and family medicine residents outperformed surgery residents in one subscale and the total score on the test. Scores were not related to year of training or attitudes toward childhood discipline but were correlated with self-reports of previous child abuse teaching. Residents' performance on a childhood disciplinary measure demonstrated wide latitude in their rating of the acceptability of 23 different modes of childhood discipline. Our findings indicate a need for a more systematic approach to residents' education in childhood intentional injuries and some value clarification of their attitudes toward various forms of childhood discipline.