Non-negative data-driven mapping of structural connections with application to the neonatal brain.

Mapping connections in the neonatal brain can provide insight into the crucial early stages of neurodevelopment that shape brain organisation and lay the foundations for cognition and behaviour. Diffusion MRI and tractography provide unique opportunities for such explorations, through estimation of white matter bundles and brain connectivity. Atlas-based tractography protocols, i.e. a priori defined sets of masks and logical operations in a template space, have been commonly used in the adult brain to drive such explorations. However, rapid growth and maturation of the brain during early development make it challenging to ensure correspondence and validity of such atlas-based tractography approaches in the developing brain. An alternative can be provided by data-driven methods, which do not depend on predefined regions of interest. Here, we develop a novel data-driven framework to extract white matter bundles and their associated grey matter networks from neonatal tractography data, based on non-negative matrix factorisation that is inherently suited to the non-negative nature of structural connectivity data. We also develop a non-negative dual regression framework to map group-level components to individual subjects. Using in-silico simulations, we evaluate the accuracy of our approach in extracting connectivity components and compare with an alternative data-driven method, independent component analysis. We apply non-negative matrix factorisation to whole-brain connectivity obtained from publicly available datasets from the Developing Human Connectome Project, yielding grey matter components and their corresponding white matter bundles. We assess the validity and interpretability of these components against traditional tractography results and grey matter networks obtained from resting-state fMRI in the same subjects. We subsequently use them to generate a parcellation of the neonatal cortex using data from 323 new-born babies and we assess the robustness and reproducibility of this connectivity-driven parcellation.

Parcel-guided rTMS for depression.

Transcranial magnetic stimulation (TMS) is an approved intervention for treatment-resistant depression (TRD), but current targeting approaches are only partially successful. Our objectives were (1) to examine the feasibility of MRI-guided TMS in the clinical setting using a recently published surface-based, multimodal parcellation in patients with TRD who failed standard TMS (sdTMS); (2) to examine the neurobiological mechanisms and clinical outcomes underlying MRI-guided TMS compared to that of sdTMS. We used parcel-guided TMS (pgTMS) to target the left dorsolateral prefrontal cortex parcel 46. Resting-state functional connectivity (rsfc) was assessed between parcel 46 and predefined nodes within the default mode and visual networks, following both pgTMS and sdTMS. All patients (n = 10) who had previously failed sdTMS responded to pgTMS. Alterations in rsfc between frontal, default mode, and visual networks differed significantly over time between groups. Improvements in symptoms correlated with alterations in rsfc within each treatment group. The outcome of our study supports the feasibility of pgTMS within the clinical setting. Future prospective, double-blind studies of pgTMS vs. sdTMS appear warranted.

A screening questionnaire for occupational and hobby exposures during pregnancy.

BACKGROUND: Occupational and environmental exposures during the prenatal period may be associated with adverse pregnancy outcomes and lifelong health effects. Yet, identification and evaluation of these potential hazards is lacking in routine obstetric care. AIMS: To assess the feasibility of incorporating a self-administered occupational and environmental exposure questionnaire into obstetric clinics. METHODS: A cross-sectional survey assessed prenatal clinic patients at a public hospital who were currently employed and <20 weeks gestation. Questionnaires evaluated job characteristics, workplace and hobby exposures, protective equipment use and symptoms during pregnancy. RESULTS: Of 69 participants (96% response rate), 46% were predominantly Spanish-speaking. Primary occupations were caregiver (16%), cleaner (14%) and administrative assistant (14%). Overall, 93% were exposed to a workplace hazard, with most participants reporting physical stressors (82%) or organic solvent exposure (78%). Most women (74%) used some personal protective equipment. Nearly half (54%) reported at least one non-pregnancy symptom, and 52% were referred for follow-up with an occupational medicine practitioner. Household and hobby-related chemical exposures were common in our sample (91%). We observed moderate consistency between job task and chemical use responses: 67-99% of intentionally redundant questions were fully or partially matched. Closed- compared to open-ended activity questions identified a higher proportion of physical stressors (82% versus 12%) and cleaning product (76% versus 30%) exposures. CONCLUSIONS: A self-administered questionnaire is an effective screening tool for identifying women with occupational and hobby-related exposures during pregnancy. Consistent incorporation of exposure assessment into prenatal care can improve clinical communications and early interventions for at-risk pregnant women.

Resting state functional connectivity predictors of treatment response to electroconvulsive therapy in depression.

There is increasing focus on use of resting-state functional connectivity (RSFC) analyses to subtype depression and to predict treatment response. To date, identification of RSFC patterns associated with response to electroconvulsive therapy (ECT) remain limited, and focused on interactions between dorsal prefrontal and regions of the limbic or default-mode networks. Deficits in visual processing are reported in depression, however, RSFC with or within the visual network have not been explored in recent models of depression. Here, we support prior studies showing in a sample of 18 patients with depression that connectivity between dorsal prefrontal and regions of the limbic and default-mode networks serves as a significant predictor. In addition, however, we demonstrate that including visual connectivity measures greatly increases predictive power of the RSFC algorithm (>80% accuracy of remission). These exploratory results encourage further investigation into visual dysfunction in depression, and use of RSFC algorithms incorporating the visual network in prediction of response to both ECT and transcranial magnetic stimulation (TMS), offering a new framework for the development of RSFC-guided TMS interventions in depression.

Diffusion of Oligonucleotides from within Iron-Cross-Linked, Polyelectrolyte-Modified Alginate Beads: A Model System for Drug Release.

An analytical model to describe diffusion of oligonucleotides from stable hydrogel beads is developed and experimentally verified. The synthesized alginate beads are Fe(3+) -cross-linked and polyelectrolyte-doped for uniformity and stability at physiological pH. Data on diffusion of oligonucleotides from inside the beads provide physical insights into the volume nature of the immobilization of a fraction of oligonucleotides due to polyelectrolyte cross-linking, that is, the absence of a surface-layer barrier in this case. Furthermore, the results suggest a new simple approach to measuring the diffusion coefficient of mobile oligonucleotide molecules inside hydrogels. The considered alginate beads provide a model for a well-defined component in drug-release systems and for the oligonucleotide-release transduction steps in drug-delivering and biocomputing applications. This is illustrated by destabilizing the beads with citrate, which induces full oligonucleotide release with nondiffusional kinetics.

The Human Connectome Project: a data acquisition perspective.

The Human Connectome Project (HCP) is an ambitious 5-year effort to characterize brain connectivity and function and their variability in healthy adults. This review summarizes the data acquisition plans being implemented by a consortium of HCP investigators who will study a population of 1200 subjects (twins and their non-twin siblings) using multiple imaging modalities along with extensive behavioral and genetic data. The imaging modalities will include diffusion imaging (dMRI), resting-state fMRI (R-fMRI), task-evoked fMRI (T-fMRI), T1- and T2-weighted MRI for structural and myelin mapping, plus combined magnetoencephalography and electroencephalography (MEG/EEG). Given the importance of obtaining the best possible data quality, we discuss the efforts underway during the first two years of the grant (Phase I) to refine and optimize many aspects of HCP data acquisition, including a new 7T scanner, a customized 3T scanner, and improved MR pulse sequences.

Are evaluated respiratory service developments implemented into clinical practice?

INTRODUCTION: Evaluation of the way in which respiratory care is delivered is increasingly recognised to be an important area for research. When service developments are reported, it is not always clear whether they are subsequently implemented within the reporting institution, and if not why not. METHODS: 3281 abstracts from three specialist journals and one general journal were reviewed, and 36 reported evaluated service developments identified. The authors of each of these were approached to determine whether the reported service developments were in use in their institution. RESULTS: 30 of the 36 authors responded (83%). 10 reports were of sharing care with nurses and five with other health professionals, and the remainder involved new technologies, education, patient information or guideline implementation. 15/30 had implemented the reported development into practice, 11 of which were implemented immediately. Delays were due to staffing, funding and organisational issues. 10/15 studies were not put into practice, the main reason being that the key person had left. Four respondents embarked upon further study to confirm their preliminary published findings. CONCLUSIONS: Reports of apparently positive service developments are only implemented in approximately one-half of institutions reporting the development. In a third of cases, non-implementation reflects the original authors believing that further study is necessary to confirm effectiveness.

Medical students' assessments of skill development in rural primary care clinics.

INTRODUCTION: This study assessed the impact of a rural primary care preceptorship on medical students' self-perceived ability to provide acute, chronic, and preventive care, to perform procedures, to communicate with patients, and to understand the community and healthcare system. METHODS: Students were surveyed about their self-assessed skills on 11 major components (97 items) immediately before and after a 16 week preceptorship in a rural primary care clinic. Responses were analyzed for 96 medical students using a paired comparisons t-test and univariate statistics. RESULTS: Students' skills significantly increased on all components and items. The skills most highly assessed post-preceptorship were those skills related to the management of chronic problems, the provision of patient education and health maintenance, and the ability to handle undifferentiated and acute problems. Among the 11 components assessed, students ranked their skills in performing procedures the lowest. The largest cumulative gain in skills was in the areas of understanding health systems and the community. CONCLUSIONS: This study provides a unique opportunity to look at skill development before and after a rural clerkship. From the student's perspective, the 16 week preceptorship appears to be of significant educational benefit. Future studies need to examine other measures of performance and outcomes of training in rural primary care settings.

Addressing issues of maldistribution of health care workers.

INTRODUCTION: The maldistribution of health care workers is a near-universal problem, particularly in developing countries. Shortages have become most critical over the past 2 decades with both out-migration of health care workers from developing to developed countries, and intra-country disparities between urban centres and rural regions. A variety of solutions have been proposed and tried, but in recent years the problem has become increasingly serious. PROGRAMME DESCRIPTION: Over the past 15 years, we have conceptualised and implemented a programme directed at the re-supply of rural physicians to our own state, Illinois, which was recently ranked as low as sixth worse in the US with regard to physician manpower shortages in rural areas. More recently, this programme has been expanded to include other health care workers where there are equivalent shortages in health services accessibility, and the entire programme is now designated as the National Center for Rural Health Professions. PROGRAMME EVALUATION: Currently, the physician programme enjoys a 65% to 70% success rate in terms of the return of physicians to rural communities; a success largely due to the unique selection process, training, and the close relationship between students and faculty. Here, we describe this programme in detail, in the hope that elements of this somewhat unique programme may be "exportable".

Lateral intermolecular forces in the physisorbed state: surface field polarization of benzene and n-hexane at the water/ and mercury/vapor interfaces.

The available experimental data on the dependence of the surface tensions of water and mercury on the adsorption of benzene and hexane from the vapor phase are critically analyzed and interpreted to obtain the two-dimensional second virial coefficients [B(2)(T)] for these adsorbed nonpolar molecules. Calculations based on the unperturbed Lennard-Jones (L-J) 12-6 formalism for benzene and the related 12-5 Salem formalism for long chains in two dimensions for hexane require that B(2)(T) should be negative for both adsorbates. On water, the experimental data indicate that B(2)(T) for both molecules is less negative than expected from the unperturbed L-J and Salem estimates, and on mercury the B(2)(T) values from experiment are positive. These findings are analyzed first in terms of a possible reduction in the attractive component of the potential of mean force between physisorbed molecules arising from their frequency-dependent interaction with their electrostatic images in the bulk phases, as described by McLachlan. It is concluded that the McLachlan corrections are small for these molecules and surfaces. A second analysis considers the effect of an extra repulsion between the adsorbed molecules arising from the induction of dipoles normal to the interface by the surface electric field. Surface field polarization (SFP) accounts reasonably well for the experimental results, leading to estimates of the surface fields at the mercury and water surfaces which are consistent with estimates from contact potentials for mercury and computation from modeling the water surface. SFP may have a wide impact in determining the form of physisorption isotherms.

Cycle of child sexual abuse: links between being a victim and becoming a perpetrator.

BACKGROUND: There is widespread belief in a 'cycle' of child sexual abuse, but little empirical evidence for this belief. AIMS: To identify perpetrators of such abuse who had been victims of paedophilia and/or incest, in order to: ascertain whether subjects who had been victims become perpetrators of such abuse; compare characteristics of those who had and had not been victims; and review psychodynamic ideas thought to underlie the behaviour of perpetrators. METHOD: Retrospective clinical case note review of 843 subjects attending a specialist forensic psychotherapy centre. RESULTS: Among 747 males the risk of being a perpetrator was positively correlated with reported sexual abuse victim experiences. The overall rate of having been a victim was 35% for perpetrators and 11% for non-perpetrators. Of the 96 females, 43% had been victims but only one was a perpetrator. A high percentage of male subjects abused in childhood by a female relative became perpetrators. Having been a victim was a strong predictor of becoming a perpetrator, as was an index of parental loss in childhood. CONCLUSIONS: The data support the notion of a victim-to-victimiser cycle in a minority of male perpetrators but not among the female victims studied. Sexual abuse by a female in childhood may be a risk factor for a cycle of abuse in males.

Indirect interaction of solid-state qubits via two-dimensional electron gas.

We propose a mechanism of long-range coherent coupling between nuclear spin qubits in semiconductor-heterojunction quantum information processing devices. The coupling is via localized donor electrons which interact with the two-dimensional electron gas. An effective interaction Hamiltonian is derived and the coupling strength is evaluated. We also discuss mechanisms of decoherence and consider gate control of the interaction between qubits. The resulting quantum computing scheme retains all the control and measurement aspects of earlier approaches, but allows qubit spacing at distances of the order of 100 nm, attainable with the present-day semiconductor device technologies.

Medical student evaluation of family nurse practitioners as teachers.

BACKGROUND: Demands on family medicine faculty to generate clinical revenue may negatively impact the undergraduate medical education program. To minimize this possibility and better model interprofessional education, family nurse practitioners (FNPs) were hired as clinicians and teachers as part of a longitudinal family medicine clerkship. This paper reports the results of a pilot study of student evaluations of nurse practitioner teaching. METHODS: All M3 and M4 students were asked to evaluate one of three FNPs who had precepted them multiple times during their previous year of ambulatory care practice. Two previously studied closed-ended questionnaires were used to assess quality of teaching by the FNPs. Students also responded to a series of open-ended questions. RESULTS: Ninety-one percent of 97 students responded to the survey. Responses to the closed-ended questions as well as comments by the students and physicians were positive regarding the teaching by FNPs. The teaching skills most highly regarded by the students tended to be different than those most highly regarded in physicians. CONCLUSIONS: This pilot study suggests FNPs can be successfully integrated into undergraduate medical education settings, offering teaching strengths that complement those of physicians. Integrating the two professions in a family medicine clerkship may prove beneficial to students and expand departmental teaching resources without further straining finances. Efforts at evaluating the teaching contributions of FNPs at other institutions are needed to substantiate the present study results.

Screening applicants for a rural medical education program.

The goal of the Rural Medical Education (RMED) Program of the University of Illinois College of Medicine at Rockford is to train rural family physicians. This article describes the screening instrument developed by RMED to identify appropriate candidates.

Illinois RMED: a comprehensive program to improve the supply of rural family physicians.

BACKGROUND: Rural areas of the United States are perennially medically underserved, and the state of Illinois is no exception. A recent survey showed that 75 of Illinois' 84 rural counties are primary care physician shortage areas. In response to this chronic physician shortage, the Illinois Rural Medical Education (RMED) Program was developed by the University of Illinois College of Medicine at Rockford. The RMED program is a comprehensive, multifaceted program that combines recruitment, admissions, curriculum, support, and evaluation components and is longitudinal across all 4 years of the medical school experience. The admissions process seeks to select students who possess traits indicative of success in eventual rural family practice. These traits are fostered and developed by the 4-year rural curriculum, which emphasizes family medicine, community-oriented primary care, the physician functioning in the context of community, relevant aspects of the "hidden" curriculum, and service learning. After 6 years, RMED has graduated 39 physicians; 69% have gone into family practice, and a total of 82% have selected primary care residencies.