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BackgroundNeonatal stroke is common and causes life-long motor and cognitive sequelae. Because neonates with stroke are not diagnosed until days-months after the injury, chronic targets for repair are needed. We evaluated oligodendrocyte maturity and myelination and assessed oligodendrocyte gene expression changes using single cell RNA sequencing (scRNA seq) at chronic timepoints in a mouse model of neonatal arterial ischemic stroke.MethodsMice underwent sixty minutes of transient right middle cerebral artery occlusion (MCAO) on postnatal day 10 (p10) and received 5-ethynyl-2’-deoxyuridine (EdU) on post-MCAO days 3-7 to label dividing cells. Animals were sacrificed 14 and 28-30 days post-MCAO for immunohistochemistry and electron microscopy. Oligodendrocytes were isolated from striatum 14 days post-MCAO for scRNA seq and differential gene expression analysis.ResultsThe density of Olig2+EdU+cells was significantly increased in ipsilateral striatum 14 days post-MCAO and the majority of oligodendrocytes were immature. Density of Olig2+EdU+cells declined significantly between 14 and 28 days post-MCAO without a concurrent increase in mature Olig2+EdU+cells. By 28 days post-MCAO there were significantly fewer myelinated axons in ipsilateral striatum. scRNA seq identified a cluster of “disease associated oligodendrocytes (DOLs)” specific to the ischemic striatum, with increased expression of MHC class I genes. Gene ontology analysis suggested decreased enrichment of pathways involved in myelin production in the reactive cluster.ConclusionsOligodendrocytes proliferate 3-7 days post-MCAO and persist at 14 days, but fail to mature by 28 days. MCAO induces a subset of oligodendrocytes with reactive phenotype, which may be a therapeutic target to promote white matter repair.

Dermatology for the pediatric skin of color population is the application of dermatology to the genetically diverse and distinctive segment of the pediatric population that includes children of non-White racial and ethnic groups with increased pigmentation including individuals of Asian, LatinX, African, Native American, Pacific Island descent, Indigenous Peoples, among others, with overlap in particular individuals, and mixtures thereof. Treating children of color is a unique skill set within the field of pediatric dermatology, requiring knowledge and sensitivity. The discipline of pediatric skin of color can be challenging. Difficulty in diagnosis of common conditions stems from underlying pigmentation, variations in common hairstyling practices, and differences in demographics of cutaneous disease, whereas some conditions are more common in children of color, other conditions have nuances in clinical appearance and/or therapeutics with regard to skin color. This article is the first in a series of two articles looking at recently published skin-related issues of high concern in children of color. Conditions reviewed in Part 1 include (1) hairstyling hair-related concerns (traction alopecia, central centrifugal cicatricial alopecia, endocrine disruption), (2) autoimmune concerns (cutaneous lupus, vitiligo), and (3) infections (tinea capitis, progressive macular hypomelanosis).

INTRODUCTION: There is no global agreement on how to best determine pregnancy of unknown location viability and location using biomarkers. Measurements of progesterone and β human chorionic gonadotropin (βhCG) are still used in clinical practice to exclude the possibility of a viable intrauterine pregnancy (VIUP). We evaluate the predictive value of progesterone, βhCG, and βhCG ratio cut-off levels to exclude a VIUP in women with a pregnancy of unknown location. MATERIAL AND METHODS: This was a secondary analysis of prospective multicenter study data of consecutive women with a pregnancy of unknown location between January 2015 and 2017 collected from dedicated early pregnancy assessment units of eight hospitals. Single progesterone and serial βhCG measurements were taken. Women were followed up until final pregnancy outcome between 11 and 14 weeks of gestation was confirmed using transvaginal ultrasonography: (1) VIUP, (2) non-viable intrauterine pregnancy or failed pregnancy of unknown location, and (3) ectopic pregnancy or persisting pregnancy of unknown location. The predictive value of cut-off levels for ruling out VIUP were evaluated across a range of values likely to be encountered clinically for progesterone, βhCG, and βhCG ratio. RESULTS: Data from 2507 of 3272 (76.6%) women were suitable for analysis. All had data for βhCG levels, 2248 (89.7%) had progesterone levels, and 1809 (72.2%) had βhCG ratio. The likelihood of viability falls with the progesterone level. Although the median progesterone level associated with viability was 59 nmol/L, VIUP were identified with levels as low as 5 nmol/L. No single βhCG cut-off reliably ruled out the presence of viability with certainty, even when the level was more than 3000 IU/L, there were 39/358 (11%) women who had a VIUP. The probability of viability decreases with the βhCG ratio. Although the median βhCG ratio associated with viability was 2.26, VIUP were identified with ratios as low as 1.02. A progesterone level below 2 nmol/L and βhCG ratio below 0.87 were unlikely to be associated with viability but were not definitive when considering multiple imputation. CONCLUSIONS: Cut-off levels for βhCG, βhCG ratio, and progesterone are not safe to be used clinically to exclude viability in early pregnancy. Although βhCG ratio and progesterone have slightly better performance in comparison, single βhCG used in this manner is highly unreliable. ispartof: ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA vol:101 issue:1 pages:46-55 ispartof: location:United States status: published

Author(s): Fung, Constance H; Martin, Jennifer L; Hays, Ron D; Col, Nananda; Patterson, Emily S; Josephson, Karen; Mitchell, Michael N; Grinberg, Austin; Aysola, Ravi; Song, Yeonsu; Dzierzewski, Joseph M; Liang, Li-Jung; Huang, David; Zeidler, Michelle; Alessi, Cathy

The James Ross Basin, in the northern Antarctic Peninsula, exposes which is probably the world thickest and most complete Late Cretaceous sedimentary succession of southern high latitudes. Despite its very good exposures and varied and abundant fossil fauna, precise chronological determination of its infill is still lacking. We report results from a magnetostratigraphic study on shelfal sedimentary rocks of the Marambio Group, southeastern James Ross Basin, Antarctica. The succession studied covers a ~1,200 m-thick stratigraphic interval within the Hamilton Point, Sanctuary Cliffs and Karlsen Cliffs Members of the Snow Hill Island Formation, the Haslum Crag Formation, and the lower López de Bertodano Formation. The basic chronological reference framework is given by ammonite assemblages, which indicate a Late Campanian – Early Maastrichtian age for the studied units. Magnetostratigraphic samples were obtained from five partial sections located on James Ross and Snow Hill islands, the results from which agree partially with this previous biostratigraphical framework. Seven geomagnetic polarity reversals are identified in this work, allowing to identify the Chron C32/C33 boundary in Ammonite Assemblage 8-1, confirming the Late Campanian age of the Hamilton Point Member. However, the identification of the Chron C32/C31 boundary in Ammonite Assemblage 8-2 assigns the base of the Sanctuary Cliffs Member to the early Maastrichtian, which differs from the Late Campanian age previously assigned by ammonite biostratigraphy. This magnetostratigraphy spans ~14 Ma of sedimentary succession and together with previous partial magnetostratigraphies on Early-Mid Campanian and Middle Maastrichtian to Danian columns permits a complete and continuous record of the Late Cretaceous distal deposits of the James Ross Basin. This provides the required chronological resolution to solve the intra-basin and global correlation problems of the Late Cretaceous in the Southern Hemisphere in general and in the Weddellian province in particular, given by endemism and diachronic extinctions on invertebrate fossils, including ammonites. The new chronostratigraphic scheme allowed us to calculate sediment accumulation rates for almost the entire Late Cretaceous infill of the distal James Ross Basin (the Marambio Group), showing a monotonous accumulation for more than 8 Myr during the upper Campanian and a dramatic increase during the early Maastrichtian, controlled by tectonic and/or eustatic causes. Fil: Milanese, Florencia Nidia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentina Fil: Olivero, Eduardo Bernardo. Universidad Nacional de Tierra del Fuego; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina Fil: Raffi, María Eugenia. Universidad Nacional de Tierra del Fuego; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Austral de Investigaciones Científicas; Argentina Fil: Franceschinis, Pablo Reinaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentina Fil: Gallo, Leandro César. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentina Fil: Skinner, Steven M.. California State University; Estados Unidos Fil: Mitchell, Ross N.. California Institute of Technology; Estados Unidos Fil: Kirschvink, Joseph L.. California Institute of Technology; Estados Unidos. Tokyo Institute of Technology; Japón Fil: Rapalini, Augusto Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Geociencias Básicas, Aplicadas y Ambientales de Buenos Aires; Argentina

Background/Objectives Home‐based primary care (HBPC) is a comprehensive, interdisciplinary program to meet the medical needs of community‐dwelling populations needing long‐term care (LTC). The U.S. Department of Veterans Affairs (VA) expanded its HBPC program to underserved rural communities, including American Indian reservations, providing a “natural laboratory” to study change in access to VA LTC benefits and utilization outcomes for rural populations that typically face challenges in accessing LTC medical support. Design Pretest‐Posttest quasi‐experimental approach with interrupted time‐series design using linked VA, Medicare, and Indian Health Service (IHS) records. Setting American Indian reservations and non‐Indian communities in rural HBPC catchment areas. Participants 376 veterans (88 IHS beneficiaries, 288 non‐IHS beneficiaries) with a HBPC length of stay of 12 months or longer. Measurements Baseline demographic and health characteristics, activities of daily living (ADL), previous VA enrollment, and hospital admissions and emergency department (ED) visits as a function of time, accounting for IHS beneficiary and functional statuses. Results For HBPC users, VA enrollment increased by 22%. At baseline, 30% of IHS and non‐IHS beneficiaries had 2 or more ADLs impairments; IHS populations were younger (P < .001) and had more diagnosed chronic diseases (P = .007). Overall, hospital admissions decreased by 0.10 (95% confidence interval (CI) = −0.14 to −0.05) and ED visits decreased by 0.13 (95% CI = −0.19 to −0.07) in the 90 days after HBPC admission (Ps < .001) and these decreases were maintained over 1 year follow‐up. Before HBPC, probability of hospital admission was 12% lower for IHS than non‐IHS beneficiaries (P = .02). Conclusion Introducing HBPC to rural areas increased access to LTC and enrollment for healthcare benefits, with equitable outcomes in IHS and non‐IHS populations.

Objectives (1) To examine relationships between frequency of nocturia and self-reported sleep quality and objective sleep measures in older women, and (2) to estimate the amount of variation in sleep measures that is specifically attributable to frequency of nocturia. Design and setting Secondary, cross sectional analysis of the multicenter prospective cohort Study of Osteoporotic Fractures (SOF). Participants Community-dwelling women aged ≥80 years. Measurements Frequency of nocturia in the previous 12 months, Pittsburgh Sleep Quality Index sleep quality subscale, and actigraphy-measured wake after sleep onset (WASO) and total sleep time (TST). Results Of 1,520 participants, 25% (n = 392) reported their nocturia frequency was 3–4 times/night and an additional 60% (n = 917) reported their nocturia frequency was 1–2 times/night. More frequent nocturia was associated with poor sleep quality (3–4/night: 26.8% reported fairly bad or very bad sleep quality; 1–2/night: 14.7%; 0/night: 7.7%; P < .001) and longer WASO (3–4/night: 89.8 minutes; 1–2/night: 70.6; 0/night: 55.5; P < .001). In nested regression models, a nocturia frequency of 3–4/night quadrupled the odds of poor sleep quality (odds ratio: 4.26 [95% CI 1.65, 11.01]; P = .003) and was associated with a 37-minute worsening in WASO (95% CI 26.0, 49.0; P < .001). Frequency of nocturia explained an additional 6% variation in WASO, above and beyond demographic, medical/psychiatric conditions, and medication factors (∆R2 = 0.06). Conclusions Nocturia is common among octogenarian and nonagenarian women and is independently associated with poor sleep quality and longer wake time at night. Interventions that improve nocturia may be useful in improving sleep quality and wake time at night.

OBJECTIVE: The M6 risk-prediction model was published as part of a two-step protocol using an initial progesterone level of ≤ 2 nmol/L to identify probable failing pregnancies (Step 1) followed by the M6 model (Step 2). The M6 model has been shown to have good triage performance for stratifying women with a pregnancy of unknown location (PUL) as being at low or high risk of harboring an ectopic pregnancy (EP). This study validated the triage performance of the two-step protocol in clinical practice by evaluating the number of protocol-related adverse events and how effectively patients were triaged. METHODS: This was a prospective multicenter interventional study of 3272 women with a PUL, carried out between January 2015 and January 2017 in four district general hospitals and four university teaching hospitals in the UK. The final pregnancy outcome was defined as: a failed PUL (FPUL), an intrauterine pregnancy (IUP) or an EP (including persistent PUL (PPUL)). FPUL and IUP were grouped as low-risk and EP/PPUL as high-risk PUL. Serum progesterone and human chorionic gonadotropin (hCG) levels were measured at presentation in all patients. If the initial progesterone level was ≤ 2 nmol/L, patients were discharged and were asked to have a follow-up urine pregnancy test in 2 weeks to confirm a negative result. If the progesterone level was > 2 nmol/L or a measurement had not been taken, hCG level was measured again at 48 h and results were entered into the M6 model. Patients were managed according to the outcome predicted by the protocol. Those classified as 'low risk, probable FPUL' were advised to perform a urine pregnancy test in 2 weeks and those classified as 'low risk, probable IUP' were invited for a scan a week later. When a woman with a PUL was classified as high risk (i.e. risk of EP ≥ 5%) she was reviewed clinically within 48 h. One center used a progesterone cut-off of ≤ 10 nmol/L and its data were analyzed separately. If the recommended management protocol was not adhered to, this was recorded as a protocol deviation and classified as: unscheduled visit for clinician reason, unscheduled visit for patient reason or incorrect timing of blood test or ultrasound scan. The classifications outlined in the UK Good Clinical Practice (GCP) guidelines were used to evaluate the incidence of adverse events. Data were analyzed using descriptive statistics. RESULTS: Of the 3272 women with a PUL, 2625 were included in the final analysis (317 met the exclusion criteria or were lost to follow-up, while 330 were evaluated using a progesterone cut-off of ≤ 10 nmol/L). Initial progesterone results were available for 2392 (91.1%) patients. In Step 1, 407 (15.5%) patients were classified as low risk (progesterone ≤ 2 nmol/L), of whom seven (1.7%) were ultimately diagnosed with an EP. In 279 of the remaining 2218 women with a PUL, the M6 model was not applied owing to protocol deviation or because the outcome was already known (usually on the basis of an ultrasound scan) before a second hCG reading was taken; of these patients, 30 were diagnosed with an EP. In Step 2, 1038 women with a PUL were classified as low risk, of whom eight (0.8%) had a final outcome of EP. Of 901 women classified as high risk at Step 2, 275 (30.5%) had an EP. Therefore, 275/320 (85.9%) EPs were correctly classified as high risk. Overall, 1445/2625 PUL (55.0%) were classified as low risk, of which 15 (1.0%) were EP. None of these cases resulted in a ruptured EP or significant clinical harm. Sixty-two women participating in the study had an adverse event, but no woman had a serious adverse event as defined in the UK GCP guidelines. CONCLUSIONS: This study has shown that the two-step protocol incorporating the M6 model effectively triaged the majority of women with a PUL as being at low risk of an EP, minimizing the follow-up required for these patients after just two visits. There were few misclassified EPs and none of these women came to significant clinical harm or suffered a serious adverse clinical event. The two-step protocol incorporating the M6 model is an effective and clinically safe way of rationalizing the management of women with a PUL. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:55 issue:1 pages:105-114 ispartof: location:England status: published

Estimated at ~58 Myr in duration, the Sturtian snowball Earth (ca. 717‐659 Ma) is one of the longest‐known glaciations in Earth history. Surprisingly few uncontroversial lines of evidence for glacial incisions associated with such a protracted event exist. We report here multiple lines of geologic field evidence for deep but variable glacial erosion during the Sturtian glaciation. One incision, on the scale of several kilometers, represents the deepest incision documented for snowball Earth; another much more modest glacial valley, however, suggests an erosion rate similar to sluggish Quaternary glaciers. The heterogeneity in snowball glacial incisions reported here and elsewhere were likely influenced by actively extending horst‐and‐graben topography associated with the breakup of supercontinent Rodinia.

Objectives To test a new cognitive behavioral therapy for insomnia (CBT-I) program designed for use by nonclinicians. Design Randomized controlled trial. Setting Department of Veterans Affairs healthcare system. Participants Community-dwelling veterans aged 60 and older who met diagnostic criteria for insomnia of 3 months duration or longer (N = 159). Intervention Nonclinician “sleep coaches” delivered a five-session manual-based CBT-I program including stimulus control, sleep restriction, sleep hygiene, and cognitive therapy (individually or in small groups), with weekly telephone behavioral sleep medicine supervision. Controls received five sessions of general sleep education. Measurements Primary outcomes, including self-reported (7-day sleep diary) sleep onset latency (SOL-D), wake after sleep onset (WASO-D), total wake time (TWT-D), and sleep efficiency (SE-D); Pittsburgh Sleep Quality Index (PSQI); and objective sleep efficiency (7-day wrist actigraphy, SE-A) were measured at baseline, at the posttreatment assessment, and at 6- and 12-month follow-up. Additional measures included the Insomnia Severity Index (ISI), depressive symptoms (Patient Health Questionnaire-9 (PHQ-9)), and quality of life (Medical Outcomes Study 12-item Short-form Survey version 2 (SF-12v2)). Results Intervention subjects had greater improvement than controls between the baseline and posttreatment assessments, the baseline and 6-month assessments, and the baseline and 12-month assessments in SOL-D (−23.4, −15.8, and −17.3 minutes, respectively), TWT-D (−68.4, −37.0, and −30.9 minutes, respectively), SE-D (10.5%, 6.7%, and 5.4%, respectively), PSQI (−3.4, −2.4, and −2.1 in total score, respectively), and ISI (−4.5, −3.9, and −2.8 in total score, respectively) (all P < .05). There were no significant differences in SE-A, PHQ-9, or SF-12v2. Conclusion Manual-based CBT-I delivered by nonclinician sleep coaches improves sleep in older adults with chronic insomnia.

The development and implementation of research-inspired, discovery-based experiences into science laboratory curricula is a proven strategy for increasing student engagement and ownership of experiments. In the novel laboratory module described herein, students learn to express, purify, and characterize a carbohydrate-active enzyme using modern techniques and instrumentation commonly found in a research laboratory. Unlike in a traditional cookbook-style experiment, students generate their own hypotheses regarding expression conditions and quantify the amount of protein isolated using their selected variables. Over the course of three 3-hour laboratory periods, students learn to use sterile technique to express a protein using recombinant DNA in E. coli, purify the resulting enzyme via affinity chromatography and dialysis, analyze the success of their purification scheme via SDS-PAGE, assess the activity of the enzyme via an HPLC-based assay, and quantify the amount of protein isolated via a Bradford assay. Following the completion of this experiment, students were asked to evaluate their experience via an optional survey. All students strongly agreed that this laboratory module was more interesting to them than traditional experiments because of its lack of a pre-determined outcome and desired additional opportunities to participate in the experimental design process. This experiment serves as an example of how research-inspired, discovery-based experiences can benefit both the students and instructor; students learned important skills necessary for real-world biochemistry research and a more concrete understanding of the research process, while generating new knowledge to enhance the scholarly endeavors of the instructor.

As an analogue of the mineral pollucite (CsAlSi2O6), CsTiSi2O6.5 is a potential host phase for radioactive Cs. However, as 137Cs and 135Cs transmute to 137Ba and 135Ba, respectively, through the beta decay, it is essential to study the structure and stability of this phase upon Cs → Ba substitution. In this work, two series of Ba/Ti-substituted samples, CsxBa(1−x)/2TiSi2O6.5 and CsxBa1−xTiSi2O7−0.5x, (x = 0.9 and 0.7), were synthesized by high-temperature crystallization from their respective precursors. Synchrotron X-ray diffraction and Rietveld analysis reveal that while CsxBa(1−x)/2TiSi2O6.5 samples are phase-pure, CsxBa1−xTiSi2O7−0.5x samples contain Cs3x/(2+x)Ba(1−x)/(2+x)TiSi2O6.5 pollucites (i.e., also two-Cs-to-one-Ba substitution) and a secondary phase, fresnoite (Ba2TiSi2O8). Thus, the CsxBa1−xTiSi2O7−0.5x series is energetically less favorable than CsxBa(1−x)/2TiSi2O6.5. To study the stability systematics of CsxBa(1−x)/2TiSi2O6.5 pollucites, high-temperature calorimetric experiments were performed at 973 K with or without the lead borate solvent. Enthalpies of formation from the constituent oxides (and elements) have thus been derived. The results show that with increasing Ba/(Cs + Ba) ratio, the thermodynamic stability of these phases decreases with respect to their component oxides. Hence, from the energetic viewpoint, continued Cs → Ba transmutation tends to destabilize the parent silicotitanate pollucite structure. However, the Ba-substituted pollucite co-forms with fresnoite (which incorporates the excess Ba), thereby providing viable ceramic waste forms for all the Ba decay products.

Background Psychological illness occurring in association with hyperemesis gravidarum (HG) has been widely reported. Objective To determine if there is a higher incidence of psychological morbidity in women with HG compared with women without significant nausea and vomiting in pregnancy. Search strategy PubMed, MEDLINE, Embase and PsychINFO were searched up to September 2015. Selection criteria Articles referring to psychological morbidity in relation to HG. For meta-analysis case–control studies using numerical scales to compare psychological symptoms. Data collection and analysis Articles were independently assessed for inclusion by two reviewers and methodology was appraised using the Newcastle Ottawa Scale. Comparison was made using the standard mean difference (SMD) in symptom scale scores. Main results In all, 59 articles were included in the systematic review, 12 of these were used in the meta-analysis. Meta-analysis of depression scale scores demonstrated a very large effect with statistically significantly higher depression scale scores in women with HG (SMD 1.22; 95% CI 0.80–1.64; P ≤ 0.01) compared with controls. Meta-analysis of anxiety scores demonstrated a large effect with statistically significantly higher anxiety disorder scale scores in women with HG (SMD 0.86; 95% CI 0.53–1.19; P ≤ 0.01). In both analyses significant heterogeneity was identified (depression and HG I2 = 94%, P ≤ 0.01; anxiety and HG I2 = 84%, P = 0.02). Conclusions Our systematic review and meta-analysis have shown a significantly increased frequency of depression and anxiety in women with HG. The findings should prompt service development for women with HG that includes provision of psychological care and support. Tweetable abstract Meta-analysis demonstrates an increase in #PsychologicalMorbidity in women with #HyperemesisGravidarum

Background Interactive and mobile technologies (i.e., smartphones such as Blackberries, iPhones, and palm-top computers) show promise as an efficacious and cost-effective means of communicating health-behavior risks, improving public health outcomes, and accelerating behavior change (Abroms and Maibach, 2008). The present study was conducted as a “needs assessment” to examine the current available mobile smartphone applications (e.g., apps) that utilize principles of ecological momentary assessment (EMA) -- daily self-monitoring or near real-time self-assessment of alcohol use behavior -- to promote positive behavior change, alcohol harm reduction, psycho-education about alcohol use, or abstinence from alcohol.

This article offers an overview of criticism of George Meredith’s poetry in the last century and a half and situates Meredith’s work within current and emergent trends in Victorian studies. The first section addresses the original critical response to Meredith’s verse and the early, influential studies that serve as the basis for later scholarship, noting the emphasis on ‘Modern Love’ to the near exclusion of Meredith’s corpus beyond that poem. It then traces the reasons for these limitations, including the access problems created by the lack of current print editions of Meredith’s poetry. Next, it surveys recent additions to Meredith criticism. The article concludes by suggesting scholarly and pedagogical directions for working with Meredith’s poetry, arguing that it is particularly well suited to the interdisciplinary, neoformalist, and narratological approaches now defining Victorian poetry scholarship.

Subjective and objective estimates of sleep are often discordant among individuals with insomnia who typically under-report sleep time and over-report wake time at night. This study examined the impact and durability of cognitive-behavioural therapy for insomnia on improving the accuracy of sleep and wake perceptions in older adults, and tested whether changes in sleep quality were related to changes in the accuracy of sleep/wake perceptions. One-hundred and fifty-nine older veterans (97% male, mean age 72.2 years) who met diagnostic criteria for insomnia disorder were randomized to: (1) cognitive-behavioural therapy for insomnia (n = 106); or (2) attention control (n = 53). Assessments were conducted at baseline, post-treatment, 6-months and 12-months follow-up. Sleep measures included objective (via wrist actigraphy) and subjective (via self-report diary) total sleep time and total wake time, along with Pittsburgh Sleep Quality Index score. Discrepancy was computed as the difference between objective and subjective estimates of wake and sleep. Minutes of discrepancy were compared between groups across time, as were the relationships between Pittsburgh Sleep Quality Index scores and subsequent changes in discrepancy. Compared with controls, participants randomized to cognitive-behavioural therapy for insomnia became more accurate (i.e. minutes discrepancy was reduced) in their perceptions of sleep/wake at post-treatment, 6-months and 12-months follow-up (p < .05). Improved Pittsburgh Sleep Quality Index scores at each study assessment preceded and predicted reduced discrepancy at the next study assessment (p < .05). Cognitive-behavioural therapy for insomnia reduces sleep/wake discrepancy among older adults with insomnia. The reductions may be driven by improvements in sleep quality. Improving sleep quality appears to be a viable path to improving sleep perception and may contribute to the underlying effectiveness of cognitive-behavioural therapy for insomnia.

A consensus about the functions of human wild-type or mutated α-synuclein (αSYN) is lacking. Both forms of αSYN are implicated in Parkinson's disease, whereas the wild-type form is implicated in substance abuse. Interactions with other cellular proteins and organelles may meditate its functions. We developed a series of congenic mouse lines containing various allele doses or combinations of the human wild-type αSYN (hwαSYN) or a doubly mutated (A30P*A53T) αSYN (hm(2) αSYN) in a C57Bl/6J line spontaneously deleted in mouse αSYN (C57BL/6JOla). Both transgenes had a functional role in the nigrostriatal system, demonstrated by significant elevations in striatal catecholamines, metabolites and the enzyme tyrosine hydroxylase compared with null-mice without a transgene. Consequences occurred when the transgenes were expressed at a fraction of the endogenous level. Hemizygous congenic mice did not exhibit any change in the number or size of dopaminergic neurons in the ventral midbrain at 9 months of age. Human αSYN was predominantly located in neuronal cell bodies, neurites, synapses, and in intraneuronal/intraneuritic aggregates. The hm(2) αSYN transgene resulted in more aggregates and dystrophic neurites than did the hw5 transgene. The hwαSYN transgene resulted in higher expression of two striatal proteins, synaptogamin 7 and UCHL1, compared with the levels of the hm(2) αSYN transgene. These observations suggest that mutations in αSYN may impair specific functional domains, leaving others intact. These lines may be useful for exploring interactions between hαSYN and environmental or genetic risk factors in dopamine-related disorders using a mouse model.

Background and purpose: Increased glutamatergic innervation of the substantia nigra pars reticulata (SNpr) and pars compacta (SNpc) may contribute to the motor deficits and neurodegeneration, respectively, in Parkinson's disease (PD). This study aimed to establish whether activation of pre-synaptic group III metabotropic glutamate (mGlu) receptors reduced glutamate release in the SN, and provided symptomatic or neuroprotective relief in animal models of PD. Experimental approach: Broad-spectrum group III mGlu receptor agonists, O-phospho-l-serine (l-SOP) and l-2-amino-4-phosphonobutyrate (l-AP4), were assessed for their ability to inhibit KCl-evoked [3H]-d-aspartate release in rat nigral prisms or inhibit KCl-evoked endogenous glutamate release in the SNpr in vivo using microdialysis. Reversal of akinesia in reserpine-treated rats was assessed following intranigral injection of l-SOP and l-AP4. Finally, the neuroprotective effect of 7 days' supra-nigral treatment with l-AP4 was examined in 6-hydroxydopamine (6-OHDA)-lesioned rats. Key results: l-SOP and l-AP4 inhibited [3H]-d-aspartate release by 33 and 44% respectively. These effects were blocked by the selective group III mGlu antagonist (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG). l-SOP also reduced glutamate release in the SNpr in vivo by 48%. Injection of l-SOP and l-AP4 into the SNpr reversed reserpine-induced akinesia. Following administration above the SNpc, l-AP4 provided neurochemical, histological and functional protection against 6-OHDA lesion of the nigrostriatal tract. Pretreatment with CPPG inhibited these effects. Conclusions and implications: These findings highlight group III mGlu receptors in the SN as potential targets for providing both symptomatic and neuroprotective relief in PD, and indicate that inhibition of glutamate release in the SN may underlie these effects.

Patients with traumatic brain injury (TBI) have delayed gastric emptying and often require prokinetic drug therapy to improve enteral feeding tolerance. The authors hypothesized that metoclopramide was less efficacious for improving gastric feeding tolerance for trauma patients with TBI compared to trauma patients without TBI. A retrospective analysis was conducted of patients admitted to the trauma or neurosurgical intensive care unit who received gastric feeding from January 2006 to April 2008. Gastric feeding intolerance was defined by a gastric residual volume >200 mL or emesis with abdominal distension or discomfort. Patients with gastric feeding intolerance were given metoclopramide 10 mg intravenously every 6 hours, followed by a dose escalation to 20 mg, and then combination therapy with metoclopramide and erythromycin 250 mg intravenously every 6 hours if intolerance persisted. In total, 882 trauma patients (49% with TBI) were evaluated. TBI patients had a higher incidence of gastric feeding intolerance than those without TBI (18.6% vs 10.4%, P < or = .001). Efficacy rates for metoclopramide 10 mg, metoclopramide 20 mg, and metoclopramide-erythromycin were 55%, 62%, and 79%, respectively (P < or = .03). Metoclopramide failure occurred in 54% of patients with TBI compared to 35% of patients without TBI, respectively (P < or = .02), due to a greater prevalence of tachyphylaxis. Single-drug therapy with metoclopramide was less effective for TBI trauma patients compared to trauma patients without TBI. Combination therapy with erythromycin as first-line therapy for TBI trauma patients with gastric feeding intolerance is indicated if there are no contraindications or significant drug interactions.

A means of deriving a disturbance index reflecting forest use history is demonstrated here to establish a disturbance gradient and enable comparison of different forest areas within and across individual forests. Detailed reference is made to Kakamega Forest in western Kenya for which a long-term time series has been established, although the study is spread to four further forests in Kenya and Uganda. A wide variety of sources are drawn upon for spatially resolved data that are integrated in a geographic information system. Three indices are derived: for commercial disturbance, local disturbance, and forest cover change. Results show a wide range of disturbance values (from low to heavy) for the research sites within Kakamega Forest, while results for Budongo and Mabira Forest sites show low and moderate levels, respectively. Correlations of low disturbance levels with nature or national reserves appear to be marked, while a correlation of disturbance with differing management authority is also suggested with Kenya Wildlife Service achieving the lowest disturbance levels. Results from the index are reviewed against other means of estimating disturbance with the conclusion that disturbance evaluations should be both spatially resolved and long-term in nature. Resume Nous montrons ici un moyen de deriver un indice de perturbation qui reflete l’utilisation historique d’une foret et qui permet d’etablir un gradient de perturbation et de comparer differentes zones forestieres au sein d’une meme foret ou entre des forets differentes. Une reference detaillee est faite a la Foret de Kakamega, dans l’ouest du Kenya, pour laquelle une suite de periodes a eteetablie dans le long terme, mais l’etude s’etend aussi a quatre autres forets en Ouganda et au Kenya. Une grande variete de sources ont servi a obtenir des donnees spatiales qui sont integrees dans un SIG. Trois indices en sont derives : pour la perturbation d’origine commerciale, la perturbation locale et le changement de couvert forestier. Les resultats revelent une large gamme de valeurs de perturbations (de faible aelevee) pour les sites de recherche dans la foret de Kakamega alors que les resultats pour les sites de Budongo et de Mabira presentent respectivement des taux faibles a moderes. Les correlations entre de faibles taux de perturbation et les reserves naturelles ou nationales semblent marquees alors qu’une correlation est aussi suggeree entre les perturbations et les differentes autorites de gestion, le Kenya Wildlife Service obtenant le plus faible taux de perturbation. Les resultats obtenus avec ces indices sont compares a d’autres moyens d’estimer les perturbations, avec la conclusion que les evaluations des perturbations devraient etre determinees spatialement et se faire sur le long terme dans la nature.

The Bologna process promises to create a unified education system in 45 countries by 2010. Is this an achievable goal? Terry Mitchell looks at the ins and outs of Bologna.

This chapter recommends an educational role for evaluators in nonformal settings, including the development of program theory and long-term evaluation capacity building.

Identification of genes involved in human cerebral development is important for our understanding of disorders with potential neurodevelopmental causes such as epilepsy and learning disability. Murine models suggest that PAX6 plays a key role in human brain development. With magnetic resonance imaging in 24 humans heterozygous for defined PAX6 mutations, we demonstrated widespread structural abnormalities including absence of the pineal gland and unilateral polymicrogyria.

It is only three years since the Bologna Declaration was signed by 29 European ministers of education. This historic document launched the process of creating a „European higher education area” by 2010. Now there are moves under way in a number of countries to revise the chemistry degree structures. The European Chemistry Thematic Network has defined a European BSc in chemistry which is presented here.