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Anti-seizure medications (ASMs) remain the mainstay of the treatment of epilepsy and the majority of patients with epilepsy (60–70%) will achieve a sustained remission from seizures. The number of ASMs has increased dramatically in recent years and there are now over 20 ASMs licensed and available . Given that epilepsy is a chronic condition, often requiring years of treatment, a choice among these drugs requires evidence about longer-term clinical and cost effectiveness, which will come largely from randomized controlled trials (RCTs), in which treatments are compared head to head. Much of this evidence comes from publically funded trials rather than those sponsored by the pharmaceutical industry, whose trials are designed to meet regulatory requirements rather than to inform clinical decision-making. In the EU this currently results in non-inferiority trials assessing six-month remission rate [2,3], whilst in the USA this resulted in short-term trials using a historical control design . More recently, the US FDA has allowed extrapolation of adjunctive therapy RCT data. Approval requires pharmacokinetic studies and recommendations for dosing to achieve levels similar to those obtained in adjunctive therapy. This approach has resulted in approvals for monotherapy for perampanel, eslicarbazepine and brivaracetam, without the need for a separate efficacy trial.
The pharynx is an important and intricate region of the body that has its developmental origin in a series of bulges found on the lateral surface of the embryonic head, the pharyngeal arches and these are a defining feature of vertebrate embryos. However, during evolution, the pharynx has also undergone extensive modifications, and these are particularly marked at three key transitions: the emergence of the vertebrates, the gnathostomes and the tetrapods. At each of these junctures the pharynx was extensively remodelled and mechanistic insights into how this was achieved can be gleaned from comparative analyses of pharyngeal development. In this chapter, we discuss the complex development of the pharynx. We consider the commonalities and differences between the pharyngeal region of vertebrates and other deuterostomes. We highlight the importance of early developmental events in the pharyngeal endoderm for laying down the fundamental organisation of this region, including the number of segments formed. Finally, we consider how the remodelling of the pharynx and the loss of pharyngeal segmentation from the adult form was achieved with the tetrapods. Overall, in this chapter we highlight the conserved and derived aspects of pharyngeal development and how these underpin the anatomy of this region.
Joe P. Buhler, Center for Communications Research, San Diego, CA 92121, USA,
Anthony C. Gamst, Center for Communications Research, San Diego, CA 92121, USA,
Ron Graham, University of California at San Diego, La Jolla, CA 92093, USA,
Alfred W. Hales, Center for Communications Research, San Diego, CA 92121, USA
We report a significant hardening of the Fermi-LAT gamma-ray spectrum from the core of Cen A at E > 2.4 GeV, suggesting there is a source of high energy particles in the core of Cen A which is in addition to the jet component. We show that the observed gamma-ray spectrum is compatible with either a spike in the dark matter halo profile or a population of millisecond pulsars. This work gives a strong indication of new gamma-ray production mechanisms in active galactic nuclei and could even provide evidence for the clustering of heavy dark matter particles around black holes.
Observational studies compare outcomes among subjects with and without an exposure of interest, without intervention from study investigators. Observational studies can be designed as a prospective or retrospective cohort study or as a case-control study. In healthcare epidemiology, these observational studies often take advantage of existing healthcare databases, making them more cost-effective than clinical trials and allowing analyses of rare outcomes. This paper addresses the importance of selecting a well-defined study population, highlights key considerations for study design, and offers potential solutions including biostatistical tools that are applicable to observational study designs.
When we contemplate ecumenism in South Africa in the twentieth century, we often automatically think of the outstanding work of the South African Council of Churches during the years of apartheid. However, it had two precursors in the General Missionary Conference of South Africa (1904–36) and the Christian Council of South Africa (1936–68). Parallel yet integral to these developments we note the significant contribution of the South African Catholic Bishops’ Conference. These did not originate or exist in a vacuum but responded to the needs and currents in society and were active in the midst of para-movements such as the Christian Institute.
Research suggests that the way in which cognitive therapy is delivered is an important factor in determining outcomes. We test the hypotheses in which the development of a shared problem list, use of case formulation, homework tasks and active intervention strategies will act as process variables.
Presence of these components during therapy is taken from therapist notes. The direct and indirect effect of the intervention is estimated by an instrumental variable analysis.
A significant decrease in the symptom score for case formulation (coefficient =–23, 95% CI –44 to –1.7, P = 0.036) and homework (coefficient =–0.26, 95% CI –0.51 to –0.001, P = 0.049) is found. Improvement with the inclusion of active change strategies is of borderline significance (coefficient =–0.23, 95% CI –0.47 to 0.005, P = 0.056).
There is a greater treatment effect if formulation and homework are involved in therapy. However, high correlation between components means that these may be indicators of overall treatment fidelity.
Despite evidence for the effectiveness of structured psychological
therapies for bipolar disorder no psychological interventions have been
specifically designed to enhance personal recovery for individuals with
recent-onset bipolar disorder.
A pilot study to assess the feasibility and effectiveness of a new
intervention, recovery-focused cognitive–behavioural therapy (CBT),
designed in collaboration with individuals with recent-onset bipolar
disorder intended to improve clinical and personal recovery outcomes.
A single, blind randomised controlled trial compared treatment as usual
(TAU) with recovery-focused CBT plus TAU (n = 67).
Recruitment and follow-up rates within 10% of pre-planned targets to
12-month follow-up were achieved. An average of 14.15 h (s.d. = 4.21) of
recovery-focused CBT were attended out of a potential maximum of 18 h.
Compared with TAU, recovery-focused CBT significantly improved personal
recovery up to 12-month follow-up (Bipolar Recovery Questionnaire mean
score 310.87, 95% CI 75.00–546.74 (s.e. = 120.34), P =
0.010, d=0.62) and increased time to any mood relapse
during up to 15 months follow-up (χ2 = 7.64,
P<0.006, estimated hazard ratio (HR) = 0.38, 95%
CI 0.18–0.78). Groups did not differ with respect to medication
Recovery-focused CBT seems promising with respect to feasibility and
potential clinical effectiveness. Clinical- and cost-effectiveness now
need to be reliably estimated in a definitive trial.
Maternal nutritional status during pregnancy has been reported to be associated with childhood asthma and atopic disease. The Avon Longitudinal Study of Parents and Children has reported associations between reduced umbilical cord Fe status and childhood wheeze and eczema; however, follow-up was short and lung function was not measured. In the present study, the associations between maternal Fe status during pregnancy and childhood outcomes in the first 10 years of life were investigated in a subgroup of 157 mother–child pairs from a birth cohort with complete maternal, fetal ultrasound, blood and child follow-up data. Maternal Fe intake was assessed using FFQ at 32 weeks of gestation and Hb concentrations and serum Fe status (ferritin, soluble transferrin receptor and TfR-F (transferrin receptor:ferritin) index) were measured at 11 weeks of gestation and at delivery. Maternal Fe intake, Hb concentrations and serum Fe status were found to be not associated with fetal or birth measurements. Unit increases in first-trimester maternal serum TfR concentrations (OR 1·44, 95 % CI 1·05, 1·99) and TfR-F index (OR 1·42, 95 % CI 1·10, 1·82) (i.e. decreasing Fe status) were found to be associated with an increased risk of wheeze, while unit increases in serum ferritin concentrations (i.e. increasing Fe status) were found to be associated with increases in standardised mean peak expiratory flow (PEF) (β 0·25, 95 % CI 0·09, 0·42) and forced expiratory volume in the first second (FEV1) (β 0·20, 95 % CI 0·08, 0·32) up to 10 years of age. Increasing maternal serum TfR-F index at delivery was found to be associated with an increased risk of atopic sensitisation (OR 1·35, 95 % CI 1·02, 1·79). The results of the present study suggest that reduced maternal Fe status during pregnancy is adversely associated with childhood wheeze, lung function and atopic sensitisation, justifying further studies on maternal Fe status and childhood asthma and atopic disease.
Accurate sea-level reconstruction is critical in understanding the drivers of coastal evolution. Inliers of shallow marine limestone and aeolianite are exposed as zeugen (carbonate-capped erosional remnants) on the southern coast of the Arabian/Persian Gulf. These have generally been accepted as evidence of a eustatically driven, last-interglacial relative sea-level highstand preceded by a penultimate glacial-age lowstand. Instead, recent optically stimulated luminescence (OSL) dating suggests a last glacial age for these deposits, requiring >100 m of uplift since the last glacial maximum in order to keep pace with eustatic sea-level rise and implying the need for a wholesale revision of tectonic, stratigraphic and sea-level histories of the Gulf. These two hypotheses have radically different implications for regional neotectonics and land–sea distribution histories. Here we test these hypotheses using OSL dating of the zeugen formations. These new ages are remarkably consistent with earlier interpretations of the formations being last interglacial or older in age, showing that tectonic movements are negligible and eustatic sea-level variations are responsible for local sea-level changes in the Gulf. The cause of the large age differences between recent studies is unclear, although it appears related to large differences in the measured accumulated dose in different OSL samples.
The Randolph Glacier Inventory (RGI) is a globally complete collection of digital outlines of glaciers, excluding the ice sheets, developed to meet the needs of the Fifth Assessment of the Intergovernmental Panel on Climate Change for estimates of past and future mass balance. The RGI was created with limited resources in a short period. Priority was given to completeness of coverage, but a limited, uniform set of attributes is attached to each of the ~198 000 glaciers in its latest version, 3.2. Satellite imagery from 1999–2010 provided most of the outlines. Their total extent is estimated as 726 800 ± 34 000 km2. The uncertainty, about ±5%, is derived from careful single-glacier and basin-scale uncertainty estimates and comparisons with inventories that were not sources for the RGI. The main contributors to uncertainty are probably misinterpretation of seasonal snow cover and debris cover. These errors appear not to be normally distributed, and quantifying them reliably is an unsolved problem. Combined with digital elevation models, the RGI glacier outlines yield hypsometries that can be combined with atmospheric data or model outputs for analysis of the impacts of climatic change on glaciers. The RGI has already proved its value in the generation of significantly improved aggregate estimates of glacier mass changes and total volume, and thus actual and potential contributions to sea-level rise.
Background: Research suggests that core schemas are important in both the development and maintenance of psychosis. Aims: The aim of the study was to investigate and compare core schemas in four groups along the continuum of psychosis and examine the relationships between schemas and positive psychotic symptomatology. Method: A measure of core schemas was distributed to 20 individuals experiencing first-episode psychosis (FEP), 113 individuals with “at risk mental states” (ARMS), 28 participants forming a help-seeking clinical group (HSC), and 30 non-help-seeking individuals who endorse some psychotic-like experiences (NH). Results: The clinical groups scored significantly higher than the NH group for negative beliefs about self and about others. No significant effects of group on positive beliefs about others were found. For positive beliefs about the self, the NH group scored significantly higher than the clinical groups. Furthermore, negative beliefs about self and others were related to positive psychotic symptomatology and to distress related to those experiences. Conclusions: Negative evaluations of the self and others appear to be characteristic of the appraisals of people seeking help for psychosis and psychosis-like experiences. The results support the literature that suggests that self-esteem should be a target for intervention. Future research would benefit from including comparison groups of people experiencing chronic psychosis and people who do not have any psychotic-like experiences.