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Among animals, diploblasts contain two germ layers, endoderm and ectoderm, while triploblasts have a distinct third germ layer called the mesoderm. Spiralians are a group of triploblast animals that have highly conserved development: they share the distinctive spiralian cleavage pattern as well as a unique source of mesoderm, the ectomesoderm. This population of mesoderm is distinct from endomesoderm and is considered a hallmark of spiralian development, but the regulatory network that drives its development is unknown. Here we identified ectomesoderm-specific genes in the mollusc Tritia (aka Ilyanassa) obsoleta through differential gene expression analyses comparing control and ectomesoderm-ablated embryos, followed by in situ hybridization of identified transcripts. We identified a Tritia serpin gene (ToSerpin1) that appears to be specifically expressed in the ectomesoderm of the posterior and head. Ablation of the 3a and 3b cells, which make most of the ectomesoderm, abolishes ToSerpin1 expression, consistent with its expression in these cells. Morpholino knockdown of ToSerpin1 causes ectomesoderm defects, most prominently in the muscle system of the larval head. This is the first gene identified that is specifically implicated in spiralian ectomesoderm development.

Summary Background Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86–1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91–1·32; p=0·21). Interpretation Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable. Funding UK Medical Research Council and Health Technology Assessment Programme.

Caudal homeobox genes are found across animals, typically linked to two other homeobox genes in what has been called the ParaHox cluster. These genes have been proposed to pattern the anterior-posterior axis of the endoderm ancestrally, but the expression of Caudal in extant groups is varied and often occurs in other germ layers. Here we examine the role of Caudal in the embryo of the mollusc Tritia (Ilyanassa) obsoleta. ToCaudal expression is initially broad, then becomes progressively restricted and is finally only in the developing hindgut (a.k.a. intestine). Knockdown of ToCaudal using morpholino oligonucleotides specifically blocks hindgut development, indicating that despite its initially broad expression, the functional role of ToCaudal is in hindgut patterning. This is the first functional characterization of Caudal in an animal with spiralian development, which is an ancient mode of embryogenesis that arose early in bilaterian animal evolution. These results are consistent with the hypothesis that the ancestral role of the ParaHox genes was anterior-posterior patterning of the endoderm.

Estimation of the prevalence of undocumented SARS-CoV-2 infections is critical for understanding the overall impact of CoViD-19, and for implementing effective public policy intervention strategies. We discuss a simple yet effective approach to estimate the true number of people infected by SARS-CoV-2, using raw epidemiological data reported by official health institutions in the largest EU countries and the USA.

To replicate and extend a study by the Agency for Healthcare Research and Quality (AHRQ) and Rutgers on antipsychotic use among youths in Medicaid, the authors analyzed Indiana Medicaid claims from 2004 to 2012, extending the earlier study by focusing on second-generation antipsychotics, including both fee-for-service (FFS) and non-FFS patients, and analyzing cost trends.The authors evaluated the impact of several Indiana Medicaid policy changes on medication utilization and cost among children enrolled for at least one month during 2004-2012 (N=683,716-793,637), using an exhaustive antipsychotic list to search the database.Annual utilization rates for antipsychotics were 2%-3% but were much higher among foster children (10%-15%). Policies implemented in 2007 or later were associated with a significant plateauing of utilization in 2008-2012.Growth of second-generation antipsychotic utilization and costs was similar to trends described in the AHRQ-Rutgers study. Several containment strategies appeared effective in addressing these trends.

Telemental health has been promoted to address long-standing access barriers to rural mental health care, including low supply and long travel distances. Examples of rural telemental health programs are common; there is a less clear picture of how widely implemented these programs are, their organization, staffing, and services. There is also a need to understand the business case for these programs and assess whether and how they might realize their promise. To address these gaps, a national study was conducted of rural telemental health programs including an online survey of 53 programs and follow-up interviews with 23 programs. This article describes the current landscape and characteristics of these programs and then examines their business case. Can rural telemental health programs be sustained within current delivery systems and reimbursement structures? This question is explored in four areas: need and demand, infrastructure and workforce, funding and reimbursement, and organizational fit and alignment.

BACKGROUND Painful vaso-occlusive crises (VOC) are the most common reason for acute care utilization in patients with sickle cell disease (SCD), and the emergency department (ED) is often the site of initial management and treatment. Treatment guidelines recommend initiation of analgesia with parenteral opioids within 30 minutes of presentation, timely reassessment of pain, and additional opioids as needed every 15-30 minutes. These targets are infrequently met, resulting in uncontrolled pain, increased likelihood of hospital admission, and deterioration of physician-patient relationships. METHODS We undertook a multidisciplinary effort to improve the management of VOC in the ED, by development and implementation of an evidence-based clinical care pathway. The clinical pathway was implemented at the Hospital of the University of Pennsylvania in December 2018, with direct education of hematology and ED providers around the content of the clinical pathway, and availability of the pathway on the institutional intranet. Specific areas of focus in the pathway included appropriate triaging of patients as emergency severity index 2, timely administration of initial opioid dose, rapid reassessment and administration of additional opioid doses as needed, as well as appropriate laboratory evaluation and evaluation for other common and/or serious complications of SCD. Outcome measures included time from ED registration to administration of first opioid dose, time between administration of first opioid dose and second opioid dose, and proportion of patients discharged from the ED. Balance measures included rate of ED readmission and length of stay. RESULTS There were 602 ED visits from 103 unique patients in the study period, with 256 visits in the six-month period prior to pathway implementation and 346 visits in the six-month period after implementation. Following pathway implementation, time from registration to first opioid dose fell from 114 minutes to 93 minutes (p = 0.003). The proportion of patients receiving their first opioid dose within 60 minutes of registration increased from 19% to 33%. Time from administration of the first opioid dose to the second opioid dose improved from 117 minutes to 94 minutes (p = 0.002). The proportion of patients receiving their second opioid dose within 60 minutes of the first opioid dose increased from 27% to 37%. There was no change in the rate of hospital admission from the ED, or in the proportion of patients who left without being seen (p = 0.710). There was also no change in rate of ED readmissions (p = 0.138) or length of stay (p = 0.483). CONCLUSION Implementation of an evidence-based clinical care pathway in the ED for SCD patients presenting with VOC led to significant improvement in outcomes, with decreased time to first opioid dose and decreased time from first to second opioid dose. Nevertheless, very few patients received guideline-based care, particularly with the goal of time to first opioid dose of less than 30 minutes. While our data demonstrate that provider education and clinical pathways clearly improve the management of VOC in the ED, additional interventions will be required to target other barriers to optimal management, including implicit biases, negative provider attitudes, and social stigma surrounding SCD. Disclosures No relevant conflicts of interest to declare.

Anatomic testing with coronary computed tomography angiography (CCTA) and functional stress testing are both appropriate first-line testing for evaluation of low to intermediate risk chest discomfort in the emergency department (ED). Real world data on rates of revascularization, time to discharge

The SCOT-HEART trial recently showed that the use of coronary computed tomography angiography (CCTA) in stable coronary artery disease (CAD) was associated with lower rates of cardiovascular death or nonfatal myocardial infarction compared to standard care. This was attributed to increased use of

Context. Perinatal palliative care is an area of increasing focus among clinicians supporting newborns and their families. Although not every newborn will survive the neonatal period, assuring their comfort and quality of life remains an imperative for their care providers. It can be challenging to administer medications such as opioids in a minimally invasive yet effective manner. Objectives. To describe the experience using intranasal (IN) fentanyl in the management of distress in a case series of 11 dying neonates. Methods. A retrospective chart review was undertaken of 58 consecutive referrals of newborns and infants aged six months or younger between November 2006 and July 2010 to the Winnipeg Regional Health Authority Pediatric Palliative Care Service to determine how often IN fentanyl was used and review documented responses after the medication. Results. Of 58 referrals, IN fentanyl was used in 11 patients, in all cases for concerns regarding respiratory distress. Chart documentation indicated that fentanyl was tolerated well, with no circumstances of drug-related apnea and no occurrences of chest wall rigidity. In most cases, labored breathing and restlessness settled after medication administration. The average time from administration of the last dose of fentanyl until death was 61 minutes. Conclusion. We found IN fentanyl, which can be administered in a variety of care settings, to be a minimally invasive means of palliating distress in dying newborns and infants. No adverse events related to its use were noted. J Pain Symptom Manage 2012;-:-e-. 2012 U.S. Cancer Pain Relief Committee. Published

Spiralian embryogenesis is found in a number of animal phyla, but the molecular mechanisms that pattern these embryos remain poorly understood. A hallmark of spiralian development is the production of tiers of cells, called quartets, that share distinct developmental potentials. Many RNAs have been discovered that are segregated into particular quartets, raising the possibility that such RNAs could be involved in establishing quartet-specific developmental potentials. In the spiralian embryo of the mollusc Ilyanassa, the IoTis11 RNA is segregated into the second and third quartets, then decays in nearly all lineages except for the ventral-anterior cells of the third quartet, 3a and 3b. Previously published fate-mapping studies, extended here, show that 3a and 3b make bilaterally symmetrical contributions to the esophagus, head ectoderm, and larval musculature. Deletion of either 3a or 3b has only mild effects on development, but ablating both cells impairs development of the esophagus and several other organs. Knockdown of IoTis11 with a translation-blocking morpholino oligonucleotide causes a very similar set of phenotypes as ablation of 3a and 3b, showing that translation of this transcript is required for normal development of 3a and 3b. These results show that a segregated RNA is necessary for the cells that inherit it in a spiralian embryo. Given that RNAs are asymmetrically segregated in nearly all the early cleavages in this embryo, these results suggest that the embryo is extensively patterned by segregated factors. Our experiments also uncovered two previously unappreciated non-autonomous events during Ilyanassa development. First, we found that the embryo can regulate to develop normal esophagus after deletion of either 3a or 3b. Second, we found that the 3a or 3b lineages are required for normal development of the digestive glands, which arise from the fourth order macromeres.

Objectives: This study investigated inpatient psychiatric units in small rural hospitals to determine their characteristics, the availability of community-based services after discharge, and the impact of the new Medicare payment system on these units. Methods: Unit managers in all rural hospitals with fewer than 50 beds that had a psychiatric unit in 2006 (N=74) were surveyed on the telephone. Results: On average these units had ten beds and 230 admissions per year. Medicare was the major payer (median of 84%). Typical staffing includes no more than one staff member from each category: psychiatrist, psychologist, social worker, counselor or therapist, and nurse practitioner. Common diagnoses reported were depression (74% of units), schizophrenia or other psychoses (42% of units), and dementia or Alzheimer’s disease (57% of units). Conclusions: Hospital staff reported little difficulty obtaining postdischarge care, and most staff clinicians provided outpatient services locally. Thus mental health services infrastructure appears better in these communities than in most rural communities, but it may be weakened by recent closures reported by some units, caused, in part, by changes in Medicare reimbursement. (Psychiatric Services 61: 620–623, 2010)

Summary During animal development, blast cell lineages are generated by repeated divisions of a mother cell into a series of daughter cells, often with a specific series of distinct fates. Nanos is a translational regulator that is involved in germline development in diverse animals [1–4] and also involved in somatic patterning in insects [5, 6]. Recently, Nanos was found to be required for maintenance of stem cell divisions in the Drosophila germline [7, 8]. We have found that in the mollusk Ilyanassa , Nanos messenger RNA and protein are specifically localized in the mesendodermal blast cell lineage derived from the strongly conserved 4d cell. Nanos activity is required for differentiation of multiple tissues that are derived from the 4d cell, showing that IoNanos is required for somatic development in this embryo. At the cellular level, we show that IoNanos activity is required for the highly stereotyped cleavage pattern of the 4d lineage, the proliferative capacity of the blast cells, and the marked asymmetry of the blast cell divisions. These results suggest that IoNanos is involved in regulating blast cell behaviors in the 4d lineage.

PUBLISHED, (213) Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD., Attention-deficit hyperactivity disorder (ADHD) is a heritable childhood onset disorder that is marked by variability at multiple levels including clinical presentation, cognitive profile, and response to stimulant medications. It has been suggested that this variability may reflect etiological differences, particularly, at the level of underlying genetics. This study examined whether an attentional phenotype-spatial attentional bias could serve as a marker of symptom severity, genetic risk, and stimulant response in ADHD. A total of 96 children and adolescents with ADHD were assessed on the Landmark Task, which is a sensitive measure of spatial attentional bias. All children were genotyped for polymorphisms (3' untranslated (UTR) and intron 8 variable number of tandem repeats (VNTRs)) of the dopamine transporter gene (DAT1). Spatial attentional bias correlated with ADHD symptom levels and varied according to DAT1 genotype. Children who were homozygous for the 10-repeat allele of the DAT1 3'-UTR VNTR displayed a rightward attentional bias and had higher symptom levels compared to those with the low-risk genotype. A total of 26 of these children who were medication naive performed the Landmark Task at baseline and then again after 6 weeks of stimulant medication. Left-sided inattention (rightward bias) at baseline was associated with an enhanced response to stimulants at 6 weeks. Moreover, changes in spatial bias with stimulant medications, varied as a function of DAT1 genotype. This study suggests an attentional phenotype that relates to symptom severity and genetic risk for ADHD, and may have utility in predicting stimulant response in ADHD., This work was supported by grants from the Irish Health Research Board, Science Foundation Ireland, the Irish Higher Education Authority's Programme for Research in Third-Level Institutions. MAB is supported by an Australian National Health and Medical Research Council Howard Florey Centenary Fellowship. KAJ is supported by the Health Research Board of Ireland.

Context:National data demonstrate that mental health (MH) visits to the emergency room (ER) comprise a small, but not inconsequential, proportion of all visits; however, we lack a rural picture of this issue. Purpose: This study investigates the use of critical access hospital (CAH) ERs by patients with MH problems to understand the role these facilities play in rural MH needs and the challenges they face. Methods: Primary data were collected through the combination of a telephone survey and ER visit logs. Our sampling frame was the universe of CAHs at the time the survey was fielded. Key Findings: About 43% of CAHs surveyed operate in communities with no MH services, while 9.4% of all logged visits were by patients identified as having some type of MH problem. The most common problems identified were affective disorders, substance abuse, anxiety, and psychotic disorders. Only 32% of CAHs have access to on-site detoxification and 2% have inpatient psychiatric services, meaning that patients in need of these services typically must leave their communities to gain treatment. Conclusions: The lack of community resources may impact CAHs’ ability to assist patients with MH problems. Among those with a primary MH condition, 21% left the ER with no or unknown treatment, as did 51% of patients whose MH condition was secondary to their emergent problem. Patients in need of detoxification or inpatient psychiatric services often must travel over an hour to obtain these services, potentially creating significant issues for themselves and their families.

Two cells (3D and 4d) in the mud snail Ilyanassa obsoleta function to induce proper cell fate. In this study, we provide support for the hypothesis that Notch signaling in Ilyanassa obsoleta functions in inductive signaling at multiple developmental stages. The expression patterns of Notch, Delta and Suppressor of Hairless (SuH) are consistent with a function for Notch signaling in endoderm formation, the function of 3D/4d and the sublineages of 4d. Veligers treated with DAPT show a range of defects that include a loss of endodermal structures, and varying degrees of loss of targets of 4d inductive signaling. Veligers that result from injection of Ilyanassa Delta siRNAi in general mimic the defects observed in the DAPT treated larvae. The most severe DAPT phenotypes mimic early ablations of 4d. However, the early specification of 4d itself appears normal and MAPK activation in both 3D/4d and the micromeres, which are known to activate MAPK as a result of 3D/4d induction, are normal in DAPT treated larvae. Treating larvae at successively later timepoints with DAPT suggests that Notch/Delta signaling is not only required during early 4d inductive signaling, but during subsequent stages of cell fate determination as well. Based on our results, combined with previous reports implicating the endoderm in maintaining induced fate specification in Ilyanassa, we propose a speculative model that Notch signaling is required to specify endoderm fates and 4d sublineages, as well as to maintain cell fates induced by 4d.

Correction to: Molecular Psychiatry (2005) 10, 831–841. doi:10.1038/sj.mp.4001684 Following publication of the above article, the authors noticed that Figure 1 did not include a color key detailing the line colors. The key is indicated in the revised figure on pages 1141–1143.

he provision of mental healthcare in rural communities has been a vexing challenge for clinicians and patients for many years. There is a chronic shortage of specialty mental health providers, particularly psychiatrists and psychologists, which has shifted much of the burden of care to primary care. Primary care clinicians have historically lacked the training and time within their busy practices to feel comfortable providing mental healthcare, particularly since the shortage of specialty mental health clinicians deprives them of consultation and referral sources. People who live in rural areas must often overcome significant travel distances, stigma, and lack of insurance and other resources to access the scarce mental health services that do exist. 1 Despite this difficult picture, rural primary care and specialty mental health clinicians have persevered to provide some level of mental healthcare to people in rural areas. Over the last decade, improvements in clinical screening tools, treatment protocols and guidelines, and information technology have significantly enhanced the potential to increase access to and improve the quality of mental health services in rural communities, particularly to underserved populations. Recent policy initiatives hold much promise to provide the structural and financial support necessary to help rural communities realize these improvements. In this commentary, we first present a general discussion of the issues related to the delivery of mental health services in the United States with particular attention to how these issues complicate the delivery of services in rural areas. Next we describe the renewed call for integrating primary care and mental health in rural areas (hence “the once and future role of primary care” in our title) and related clinical and policy support to do so. We close by briefly describing the policy interventions and resources needed to further these integration efforts and to improve access to services for rural underserved populations. Our Fragmented Mental Health Delivery System The mental health delivery system in the United States is characterized by a fragmentation of services, separation of funding streams and delivery systems, poor reimbursement, inadequate access to specialty mental health providers, and the mal-distribution of existing resources. These issues greatly complicate the delivery of services in rural areas. The United States mental health system is not a coordinated system of specialty mental health services but, rather, a fragmented collection of services and providers that has come to be known as

An association has been reported between Wiskott-Aldrich syndrome and necrotizing vasculitis and aneurysmal arterial dilatation. We present here the first endovascular repair of descending thoracic aortic aneurysm in a 35-year-old male patient with the classical Wiskott-Aldrich syndrome phenotype. He had a successful endovascular repair with early discharge from hospital with no postoperative complications. His 1-year follow-up computed tomography scan confirmed appropriate stent position, aneurysm sac resolution with no evidence of endoleak, and no further aneurysm formation.

As of 2000, 21 states had implemented Medicaid managed behavioral health (MMBH) programs for a significant portion of their rural population. It is not clear how MMBH programs may work in rural areas since they are primarily designed to control mental health utilization. In rural areas the challenge is often to enhance service delivery, not to reduce it. MMBH programs may also affect important features of rural delivery systems, including access to care and coordination of primary care and specialty mental health providers. This article describes the implementation of MMBH programs in rural areas based on an inventory of states implementing MMBH programs in rural counties conducted between June 1999 and June 2000. The experience of MMBH programs in rural areas is also described based on case studies conducted in six states. All 21 states included the general Medicaid population (Temporary Assistance for Needy Families); 17 states included special Medicaid populations (adults with serious and persistent mental illness and children with serious emotional disturbances). Slightly less than half the states integrated (carved-in) behavioral health with physical health services in serving the general Medicaid population; only one state integrated these services for the special Medicaid population. Access to mental health care in rural areas had generally not been restricted. MMBH had little impact on the linkage between primary care and mental health. Local Managed Behavioral Health Organizations, formed by public sector entities and providers, played an increasingly important role in the evolution of MMBH.

Introduction: the diagnosis of thoracic outlet syndrome (TOS) relies heavily on subjective rather than objective assessment criteria. Subsequently, published results after surgical decompression vary considerably. This study aimed to use a symptom-based patient-directed questionnaire to assess the outcome after decompression for TOS. Methods: sixty patients who underwent decompression procedures were identified from a prospectively maintained vascular database. Patient records were analysed for details regarding initial presentation, investigation, type of procedure used for decompression and management. Outcome questionnaires were sent to all identified patients to give a patient-based outcome measure. Results: eighty-four per cent of patients responded. In 90% of these patients there was an improvement in symptoms post-surgery with a median follow up of 43 months. The results were not influenced by the procedure or approach used. Conclusion: surgery remains an effective tool in the management of TOS. A simple patient-directed questionnaire as used in this study could assist in the standardisation of outcome assessment. Eur J Vasc Endovasc Surg 26 , 170-175 (2003)

Guided by a life course perspective, this study examined the effects of transitioning into caregiving activity for a child, spouse, parent, other relative, or nonkin associate on nine dimensions of psychological well-being. Data came from adults ages 19-95, who were noncaregiver primary respondents in the National Survey of Families and Households in 1987-88 and who were followed up longitudinally in 1992-93 (N = 8,286). Results from multivariate regression models confirmed that the transition to caregiving for primary kin (i.e., a child, spouse, or biological parent) was associated with an increase in depressive symptoms. However in selected instances, caregiving was associated with beneficial effects (e.g., women who began to provide nonresidential care to a biological parent reported more purpose in life than noncaregiving women). Evidence regarding gender differences was inconsistent, varying across caregiving role relationship types. Key Words: caregiving, depression, gender, life course, psychological well-being, transition. The likelihood of becoming a caregiver for a family member or friend with a disabling mental or physical health condition during the adult life course is increasing for both women and men (Brody, 1990; Marks, 1996; Stone, Cafferata, & Sangl, 1987). As public awareness has grown about the prevalence and social significance of informal care provision during the last two decades, caregiving research has mushroomed-particularly research on geriatric caregiving for aging parents and spouses (see Biegel, Sales, & Schulz, 1991; Chappell, 1990; Gallagher-Thompson, Coon, Rivera, Powers, & Zeiss, 1998; Horowitz, 1985; Schulz, O'Brien, Brookwala, & Fleissner, 1995; Schulz, Visintainer, & Williamson, 1990, for reviews). Overall, most studies have concluded that caregiving is associated with an increased sense of burden and psychological distress (e.g., Anthony-Bergstone, Zarit, & Gatz, 1988; George & Gwyther, 1986; Hoyert & Seltzer, 1992; Schulz & Williamson, 1991; Strawbridge, Wallhagen, Shema, & Kaplan, 1997). Gender differences in the effects of caregiving have also been a prominent topic of research interest. Although there is not total consistency in results across studies, the predominance of evidence from research to date suggests that women experience more burden and psychological distress in the caregiving role than men (see Miller & Cafasso, 1992; Montgomery, 1992; Stoller, 1992, Yee & Schulz, 2000, for reviews). Informal caregiving is provided by a wide range of role partners-parents, spouses, adult children, adult children-in-law, other relatives, and nonkin (Barker & Mitteness, 1990; Cantor, 1979; Gerstel & Gallagher, 1993; Marks, 1996, 1998; Neal, Chapman, Ingersoll-Dayton, & Emlen, 1993; Stone et al., 1987). However, relatively few studies have differentiated and examined multiple role relationship types of caregiving (Neal et al. 1993; Seltzer & Li, 2000), even though existing research suggests role relationship type, like gender, is an important moderator of caregiving effects (Biegel et al., 1991). The most typical caregiving role relationship difference examined thus far is between spouse and filial caregivers. Overall, spousal caregivers have been found to experience more negative effects from caregiving than filial caregivers (Biegel et al., 1991; George & Gwyther, 1986; Seltzer & Li, 2000; Young & Kahana, 1989). Additionally, parents providing care for a child with a disability sometimes have been found to experience higher levels of stress in comparison to other types of caregivers (Biegel et al.); however, the evidence on this issue remains mixed (Neal et al., 1993). Only a few studies have explored differences between giving care to a parent and giving care to a parent-in-law, yielding inconsistent results. Spitze, Logan, Joseph, and Lee (1994) found more distress occurred when caring for a biological parent, Ingersoll-Dayton, Starrels, and Dowler (1996) found no differences in caregiver stress, and Peters-Davis, Moss, and Pruchno (1999) found only a few differences. …

This paper argues that white Barbadian responses to the renewed anti-slavery campaign from 1823 to 1825 were characterized by a combination of strident assertions of loyalty with a more hostile rhetoric of difference and distance. Drawing on work that emphasizes the place of the anti-slavery campaign in the formulation of English identity, this paper considers where such accounts leave white West Indians, and argues that opposition to anti-slavery was linked to the production of white identity in Barbados. It seeks to explore the complex nature of white resistance to anti-slavery, and thus the ambiguous nature of West Indian whiteness, by focusing on a series of texts produced in the aftermath of ameliorative instructions sent out by the British government and of a major slave revolt in Demerara. In particular, it considers a series of anonymous texts produced during a period of intense anti-Methodist persecution. Locating this anti-Methodism within the broader context of opposition to the anti-slavery campaign, these texts encapsulate the ambivalence of identity and difference, loyalty and hostility that characterizes West Indian whiteness in the early nineteenth century. In this way, the paper aims to contribute to a more nuanced historical geography of white identity.

We have completed the first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder. The first stage screening sample included 509 subjects from 151 nuclear families recruited within the United Kingdom and Republic of Ireland. This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI) and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or MDD(R)), approximately two thirds of all families contained at least one other additional typed individual. All individuals were genotyped using 398 highly polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set Version 2. The average inter-marker distance was 9.6 cM and the mean heterozygosity was 0.78. Analysis of these data using non-parametric linkage methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage. We identified 19 points across the genome where the MLS exceeded a value set for follow up in our second stage screen (MLSor = 0.74 (equivalent to a nominal pointwise significance of 5%) under the narrowest diagnostic model). These points were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18X. Some of these points overlapped with previous linkage reports both within bipolar affective disorder and other psychiatric illnesses. Under the narrowest diagnostic model, the single most significant multipoint linkage was on chromosome 18 at marker D18S452 (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125, under the broadest diagnostic model.

A naturalistic, prospective study of the influence of genetic variation on dose prescribed, clinical response, and side effects related to stimulant medication in 77 children with attention-deficit/hyperactivity disorder (ADHD) was undertaken. The influence of genetic variation of the CES1 gene coding for carboxylesterase 1A1 (CES1A1), the major enzyme responsible for the first-pass, stereoselective metabolism of methylphenidate, was investigated.Parent- and teacher-rated behavioral questionnaires were collected at baseline when the children were medication naïve, and again at 6 weeks while they were on medication. Medication dose, prescribed at the discretion of the treating clinician, and side effects, were recorded at week 6. Blood and saliva samples were collected for genotyping. Single nucleotide polymorphisms (SNPs) were selected in the coding, non-coding and the 3' flanking region of the CES1 gene. Genetic association between CES1 variants and ADHD was investigated in an expanded sample of 265 Irish ADHD families. Analyses were conducted using analysis of covariance (ANCOVA) and logistic regression models.None of the CES1 gene variants were associated with the dose of methylphenidate provided or the clinical response recorded at the 6 week time point. An association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate was found. The two associated CES1 markers were in linkage disequilibrium and were significantly associated with ADHD in a larger sample of ADHD trios. The associated CES1 markers were also in linkage disequilibrium with two SNP markers of the noradrenaline transporter gene (SLC6A2).This study found an association between two CES1 SNP markers and the occurrence of sadness as a side effect of short-acting methylphenidate. These markers were in linkage disequilibrium together and with two SNP markers of the noradrenaline transporter gene.

Despite the prevalence and consequence of depression in rural areas, the literature on treating depression in rural areas is relatively scarce and inconclusive. The use of mental health services by rural people suffering from depression and the role that supply may play in explaining these differences are not well understood. Understanding these issues for rural Medicaid beneficiaries is important as Medicaid managed care for physical and behavioral health care is expanded to rural areas. This study compares the mental health service use of rural and urban Medicaid beneficiaries, ages 18 to 64, in Maine suffering from depression and examines what influence mental health and primary care supply have in explaining observed differences. Two models are used to estimate the use of ambulatory mental health services: (1) a logit likelihood estimate of whether a beneficiary uses any outpatient mental health services for depression; (2) an ordinary least squares regression estimating the number of annualized ambulatory mental health care visits among users. Rural beneficiaries suffering from depression have lower utilization than urban beneficiaries. Rural and urban Aid for Families with Dependent Children (AFDC)- and Supplemental Security Income (SSU-beneficiaries suffering from depression rely more on mental health than on general health care providers to receive ambulatory mental health care. Rural beneficiaries (AFDC and SSI) rely relatively more on general health care providers than urban beneficiaries. Multivariate analysis suggests that mental health supply and patient-level factors, but not primary care supply, account for utilization differences. This article describes the need to better understand factors limiting participation of primary care providers and to study the role of supply across multiple states.

This paper presents findings from a study designed to identify and describe models for integrating primary care and mental health services in rural communities. Data were obtained from telephone interviews with staff at rural primary care sites around the country. Findings are based on the responses of 53 primary care organizations in 22 states. The authors identify four integration models—diversification, linkage, referral and enhancement—which appear to exist in combination, rather than as pure types. The proposed analytic framework outlines aspects of integration that are readily amenable to study.

The giant otter Enhydritherium terraenovae, a New World taxon thought to be related to both the Old World otter Enhydriodon and the extant sea otter Enhydra, was originally described on the basis of relatively limited material, mostly dental. However, an incomplete skeleton of E. terraenovae recovered from the early Hemphillian Moss Acres Racetrack site in northern Florida includes a skull, mandible, part of the axial skeleton, and most of both the fore- and hindlimbs, adding greatly to knowledge of this animal. On the basis of this new material, the osteology of this species is described in detail for the first time, with its diagnosis revised accordingly. This new osteological information, along with information about the nature of the Moss Acres Racetrack site, allows such paleoecological and functional aspects of E. terraenovae as habitat preference, mode of swimming, and diet to be inferred or interpreted in a detail previously impossible. E. terraenovae: 1) was a habitat generalist rather t...

Purpose: An automated TLD facility has been commissioned and calibrated, and techniques have been developed for the measurement of exit doses in external beam radiotherapy, to enable the routine estimation of delivered tumor doses. Methods and Materials: An automated TLD system, originally intended for use in diagnostic radiology and radiation protection, has been evaluated and configured for the measurement of exit doses in radiotherapy. Linearity, optimum heating cycles and calibration procedures have been determined. At the photon energies used, encapsulated lithium fluoride chips provide insufficient buildup to ensure electronic equilibrium, necessitating calibration to allow for oblique exit surfaces. Expressions are derived to allow the calculation of delivered tumor doses. Results: Under the calibration conditions described, the uncertainty in a single TLD measurement is approximately ±2% (±1 standard deviation ). Over the dose range 0.4-1.5 Gy, TL response is linear. The total heating cycle time, including annealing, is 75 s. Measurements of R exit (the ratio of exit dose with and without full backscatter), used in the estimation of tumor doses, decreases with field size for small fields and varies only slightly for field sizes greater than 7 × 7 cm. Lack of electronic equilibrium leads to a decrease in R exit with increasing exit surface obliquity for all energies considered. Application of the technique to a simulated treatment showed good agreement between estimated and applied tumor doses, when surface obliquity was taken into account. Conclusion: This work describes the commissioning and calibration of an automated TLD facility and demonstrates that exit surface measurements using TLD chips used under conditions where electronic equilibrium was not established, have the potential for identifying discrepancies in delivered tumor doses.

Over a 5-year period a prospective audit was carried out on 1131 patients undergoing surgery for abdominal aortic aneurysm (AAA) in the northern region. A total of 470 operations was performed in teaching hospitals and 661 in district hospitals; emergency operations accounted for 41-5 per cent. The overall mortality rate was 25.8 per cent; for emergency cases this value was 50.0 per cent. Mortality rates for elective surgery were 3.9 per cent in teaching and 12.0 per cent in district hospitals. Patients with ruptured AAA admitted via the accident and emergency department had a higher mortality rate (64.3 per cent) than those admitted by their general practitioner (49.5 per cent) or those referred from the urology department (18.8 per cent). In all, 73 (6.5 per cent) patients were admitted with an alternative diagnosis, ranging from collapse of unknown cause (25) to torsion of the testes (one) and colonic obstruction (one). Age had a profound effect on mortality rates. For emergency cases the mortality rate varied from 47.0 per cent (in teaching plus district hospitals) in those aged less than 80 years to 70.1 per cent in those 80 years or over (χ2 = 7.22; P = 0.007). For elective surgery the mortality rate varied from 7.6 per cent (in teaching plus district hospitals) in those under 80 years to 23.8 per cent in those 80 years or over (P = 0.0006). The overall mortality rate of 25.8 per cent is significantly less than that quoted in the Confidential Enquiry into Perioperative Deaths report of 1987. Furthermore, elective patients over 80 years of age may expect a survival rate of 76 per cent and, in the absence of major medical contraindications, should not automatically be denied surgery. Importantly, it is of note that this prospective audit identified 31 per cent more cases than recognized by regional audit data.

A life-course theoretical perspective guided this study to examine how effects on mental and physical health (depressive symptoms, hostility, global happiness, self-esteem, personal mastery, psychological wellness, self-rated physical health) of transitioning into filial caregiving for a sole surviving parent are moderated by prior relationship quality, filial obligation, race or ethnicity, education, income, employment status, marital status, and parental status. Results from models estimated using longitudinal data from 1,060 adults aged 25 to 65 years at baseline (National Survey of Families and Households, 1987 to 1994) suggested that life-course and contextual factors do contribute to patterning health risks of caregiving, often in different ways for men and women: For example, low income puts daughter caregivers at greater risk for decline in physical health, combining employment with filial caregiving is more problematic for daughters' mental health, and being an unmarried filial caregiver is more problematic for men. Heterogeneity in the experience of filial care needs further attention in future research.

PUBLISHED, PMID: 18361436, Funded by: Health Research Board of Ireland and Science Foundation Ireland

This study aimed to assess the dosimetric impact of setup errors during the delivery of radiotherapy to the breast, and use this information to make recommendations on intervention tolerances for portal imaging of breast treatments. Translational and rotational setup errors were simulated for 10 recent breast patients using an Oncentra MasterPlan treatment planning system. The effect of these errors on the breast and tumor bed target volumes receiving 95% and 107% of the prescribed dose were assessed. For the majority of patients, shifts of up to 10 mm or a 4 degrees patient rotation about the cranio-caudal axis had no significant effect on the dose distribution. Changes in dosimetry were more likely if the reference plan contained large hot or cold spots. For a typical patient, it is estimated that a shift of 5 mm in any one direction, or a 2 degrees patient rotation would not cause more than a 5% change in the target volume receiving between 95% and 107% of the prescribed dose. If combinations of errors occur, greater dosimetric changes would be expected. It is concluded that individual patient shifts of up to 5 mm or rotations about the cranio-caudal axis of 2 degrees or less are unlikely to affect dose-volume histogram parameters by an amount judged as clinically significant. Setup errors exceeding these values may cause large dosimetric changes for some patients, particularly those with larger hot or cold regions in the dose distribution, and intervention is therefore recommended.

The Spiralia is a clade of protostome invertebrate phyla that share a highly conserved mode of early development. Spiralian development is characterized by regularities in the arrangement of early cleavages, the fates of the cells that are produced by these divisions, and the development of the distinctive trochophore larva. Because of the strong conservation in early development, homologies can be identified between cells in divergent taxa. Some of the most striking examples of conservation in the spiralian embryo are in the cells that generate the mesoderm. The specification of the mesodermal precursors has been well characterized by embryological approaches, and recently the molecular mechanisms of mesoderm specification are starting to be elucidated. This review examines the development of mesoderm in spiralians in a comparative context, with particular focus on the relationship between the mesendodermal cell 4d and the embryonic organizer.

In everyday life, our sensory system is bombarded with visual input and we rely upon attention to select only those inputs that are relevant to behavioural goals. Typically, humans can shift their attention from one visual field to the other with little cost to perception. In cases of 'unilateral neglect', however, there is a persistent bias of spatial attention towards the same side as the damaged cerebral hemisphere. We used a visual orienting task to examine the influence of functional polymorphisms of the dopamine transporter gene (DAT1) on individual differences in spatial attention in normally developing children. DAT1 genotype significantly influenced spatial bias. Healthy children who were homozygous for alleles that influence the expression of dopamine transporters in the brain displayed inattention for left-sided stimuli, whereas heterozygotes did not. Our data provide the first evidence in healthy individuals of a genetically mediated bias in spatial attention that is related to dopamine signalling.

Historically the divisions between the mental health and substance abuse fields have been so deep that attempts to provide coordinated treatment across service sectors for people with dual diagnoses of psychiatric disorder and substance use disorder have failed. The authors describe a program in Maine designed to develop collaboratives, or communities of providers, who work together to offer coordinated mental health and substance abuse treatment and support. Surveys of provider agencies in one collaborative conducted one year and two years after the collaborative was established showed an increase in interagency referrals, joint assessments of clients, and jointly sponsored training and client services.

Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD=3.30) and D10S197 (LOD=3.18). Multipoint analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16–q21 (MLS=2.61) and 4q12–q21 (MLS=2.38). 6q16–q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male–male pairs. Our scan also provides support for linkage (MLS1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14–p12 and 18q22.

PUBLISHED, Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches.

Objectives: The authors sought to gain further perspective on discrimination experienced by persons with mental illness by comparing selfreports of discrimination due to mental illness to self-reports of discrimination due to other group characteristics, such as race, gender, and sexual orientation. Methods: A total of 1,824 persons with serious mental illness who participated in a baseline interview for a multistate study on consumer-operated services completed a two-part discrimination questionnaire. The first part of the questionnaire assessed participants’ perceptions about discrimination due to mental illness as well as more than half a dozen other group characteristics. The second part of the questionnaire asked participants who reported some experience with discrimination to identify areas in which this discrimination occurred, such as employment, education, and housing. Results: More than half of the study participants (949 participants, or 53 percent) reported some experience with discrimination. The most frequent sources of this discrimination were mental disability, race, sexual orientation, and physical disability. Areas in which discrimination frequently occurred included employment, housing, and interactions with law enforcement. Areas in which discrimination was experienced did not significantly differ among groups of study participants characterized by mental disability, race, gender, sexual orientation, or physical disability. Conclusions: Discrimination based on group characteristics other than mental illness does not diminish the impact of stigma associated with mental illness. Antistigma programs need to target not only discrimination related to mental illness but also that associated with other group characteristics, such as race, gender, sexual orientation, and physical disability. (Psychiatric Services 54:1105–1110, 2003)

Background and Purpose — The goal of this study was to determine the efficacy of CT angiography for the characterization of plaque morphology and composition in carotid atherosclerotic disease. Methods — Fifty-five patients undergoing carotid endarterectomy were imaged preoperatively with single-slice spiral CT angiography. One hundred sixty-five endarterectomy sections were examined histologically at selected levels through the distal common and proximal internal carotid arteries. Plaque density was measured (in Hounsfield units) on axial CT sections, and the presence or absence of ulceration was noted. These observations were compared with the histological findings at corresponding levels. Data were analyzed with 2-sample t tests and 1-way analysis of variance (ANOVA). Results — ANOVA testing showed a statistically significant decrease in CT attenuation values with increasing plaque lipid but with a very high standard deviation of values. No other histological factor showed a statistically significant link with CT attenuation. Plaque ulceration was detected by CT with a sensitivity of 60% and a specificity of 74%. Conclusions — Analysis of plaque attenuation with single-slice spiral CT does not give useful information concerning plaque composition. The predictive value of CT for the detection of plaque ulceration was moderate. Single-slice CT angiography is insufficiently robust to be a useful tool for the characterization of carotid plaque composition and morphology.

• Administration of intranasal fentanyl to newborns and infants at end-of-life is safe and effective in managing respiratory distress • Intranasal fentanyl is useful in a variety of care settings (hospital and home) for the management of symptoms in newborns and infants at end-of-life • Identified the need to address logistical issues, which include: development of a guideline for the availability of the medication; the use of an atomizer in nasal medication delivery; and supporting staff in this approach to managing symptoms in newborns and infants at end-of-life. Use of Intranasal Fentanyl in Palliative Care of Newborns and Infants