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Patients with bipolar disorder experience a wide range of depressive and manic symptoms. Only 2 drugs are FDA-approved to treat episodes of both mania and depression in patients with bipolar disorder, highlighting the need for treatments with proven efficacy at opposite poles of the bipolar spectrum. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist and serotonin 5-HT1A receptor partial agonist, is approved in the US for the treatment of both bipolar depression and manic and mixed episodes associated with bipolar I disorder. Cariprazine has previously demonstrated broad efficacy in patients with bipolar mania, with significantly greater improvement in favor of cariprazine vs placebo (PBO) across all individual symptom domains (P<.001) measured by the Young Mania Rating Scale (YMRS). Additionally, cariprazine has demonstrated efficacy vs PBO in 3 phase II/III clinical studies in patients with depressive episodes associated with bipolar I disorder (NCT01396447, NCT02670538, NCT02670551). To further assess the broad efficacy of cariprazine in patients with bipolar I disorder, we performed post hoc analyses to evaluate the range of depressive symptoms comprising the individual items of the Montgomery-Åsberg Depression Rating Scale (MADRS) in patients from the bipolar depression studies.
Data from the 3 randomized, double-blind, PBO-controlled trials in patients with bipolar depression were pooled. Least squares (LS) mean change from baseline to week 6 in MADRS individual items was assessed in the pooled cariprazine 1.5 and 3 mg/d groups vs PBO using a mixed-effects model for repeated measures in the intent-to-treat (ITT) population.
There were 1383 patients in the ITT population (placebo=460; cariprazine 1.5-3 mg/d=923). At week 6, LS mean change from baseline was significantly greater for cariprazine 1.5-3 mg/d vs PBO on 9 of 10 individual MADRS items: Apparent Sadness (-2.0 vs -1.6, P<.0001); Reported Sadness (-2.0 vs -1.6, P<.0001); Reduced Sleep (-1.6 vs -1.4, P=.0357); Reduced Appetite (-1.2 vs -1.0, P=.0001); Concentration Difficulties (-1.5 vs -1.2, P=.0002); Lassitude (-1.7 vs -1.4, P=.0003); Inability To Feel (-1.7 vs -1.5, P=.0009); Pessimistic Thoughts (-1.4 vs -1.2, P=.0054) and Suicidal Thoughts (-0.3 vs -0.2, P=.0383); differences between cariprazine and PBO on the Inner Tension item were not significant.
Significant improvement in most MADRS single items suggests broad efficacy in depressive symptoms for cariprazine 1.5-3 mg/d vs PBO in patients with bipolar depression. Coupled with broad efficacy in manic symptoms as demonstrated by significant improvement in all YMRS individual items in patients with bipolar mania or mixed episodes, cariprazine appears be effective across the range of symptoms that affect patients with bipolar disorder.
Endoscopes provide a magnified view of the middle ear and visualisation of hidden areas. Otoendoscopes facilitate excellent visualisation of the round window niche during cochlear implantation.
To compare microscopic and endoscopic visualisation of the round window membrane during cochlear implantation in 20 patients.
Twenty patients who underwent cochlear implantation were included in the study. After maximum exposure of the round window, the accessibility of the round window membrane was graded according to the St Thomas Hospital classification, first by microscope and then by endoscope.
With the use of the endoscope, visualisation of the round window membrane improved in all the patients as compared to the microscope. The electrode array was inserted via a round window or extended round window approach in all but two cases; the latter cases required bony cochleostomy because of unfavourable anatomy.
The main benefit of endoscope-assisted cochlear implantation is improved visibility of the round window region.
To study 2D and 3D dosimetric values for bladder and rectum, and the influence of bladder volume on bladder dose in high dose rate (HDR) intracavitary brachytherapy (ICBT). The large patient data incorporated in this study would better represent the inherent variations in many parameters affecting dosimetry in HDR-ICBT.
Material and Methods:
We prospectively collected data for 103 consecutive cervical cancer patients (over 310 HDR fractions) undergoing CT-based HDR-ICBT at our centre. Correlation among bladder and rectum maximum volume doses and corresponding International Commission on Radiation Units and Measurement (ICRU) point doses were estimated and analysed. Impact of bladder volume on bladder maximum dose was assessed.
The ICRU point doses to bladder and rectum varied from the volumetric doses to these organs. Further, bladder volume poorly correlated with bladder maximum dose for volume variations encountered in the clinical practice at our centre.
ICRU point doses to bladder and rectum are less likely to correlate with long-term toxicities to these organs. Further, in clinical practice where inter-fraction bladder volume does not vary widely there is no correlation between bladder volume and bladder dose.
Background: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological entity associated with multiple etiologies including infection, metabolic, and epileptic disorders. We describe the case of a child with a reversible splenial lesion who presented with encephalopathy and prior history of episodic ataxia. Methods: A 3-year-old girl presented to the Stollery Children’s hospital with three days of respiratory symptoms followed by acute onset ataxia and encephalopathy. Blood, respiratory samples, and cerebral spinal fluid (CSF) were drawn to investigate for infectious, autoimmune, and metabolic causes. Magnetic resonance imaging (MRI) brain was done and repeated. Results: A respiratory panel tested positive for respiratory syncytial virus (RSV), enterovirus, and rhinovirus. CSF analysis revealed elevated white blood cell count (283). MRI brain demonstrated diffusion restriction involving the posterior body and splenium of the corpus callosum and bilateral middle cerebral peduncles, which resolved nine days later. The patient received high-dose steroids with gradual improvement in the encephalopathy and ataxia. Conclusions: This report contributes to the complexities in clinical understanding of RESLES, as it highlights a novel presentation with ataxia and encephalopathy. The patient’s diagnosis was complicated by previous ataxic episodes of unknown etiology, which allows further consideration of a metabolic or genetic ataxic syndrome and its relationship to encephalopathy.
Background: Gliomas demonstrate epigenetic dysregulation highlighted by the Glioma CpG-Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. IDH1 mutation perturbs the balance between 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) by inhibiting TET-mediated active demethylation. The role 5hmC plays in IDH1 mutant tumors remains poorly understood. Methods: We profiled 5hmC in high grade IDH1 mutant (n = 12) and wild-type (n = 9) tumors on the Illumina MethylationEPIC Beadchip. We examined regions with high 5hmC abundance (top 1% probes), and differentially hydroxymethylated regions (DHMR). 5hmC profiles were correlated with gene expression. Results: Mean 5hmC b-values were 4.6%% and 3.8% for IDH1 mutant and wild-type tumors, respectively. Top 1% and DHMR probes demonstrated increased 5hmC among IDH1 mutants. 5hmC enriched for enhancer and super-enhancers. Among G-CIMP target genes, 22/50 were hydroxymethylated in our IDH1 mutant cohort, suggesting that 5hmC contributes to their overall methylation. Gene expression was associated with gene body 5hmC. 48 genes differentially expressed between IDH1 cohorts showed a positive Spearman correlation between 5hmC and gene expression, in particular for genes upregulated in IDH1 mutants. Conclusions: Locus-specific gain of 5hmC, targeting regulatory regions and associated with over-expressed genes, suggests a significant role for 5hmC in IDH1 mutant HGG.
This study compared the therapeutic efficacy of steroidal and non-steroidal agents for treating oral lichen planus.
Forty patients with clinical and/or histologically proven oral lichen planus were randomly placed into four groups and treated with topical triamcinolone, oral dapsone, topical tacrolimus or topical retinoid for three months. Pre- and post-treatment symptoms and signs were scored for each patient.
Patients in all treatment groups showed significant clinical improvement after three months (p < 0.05), with steroidal and non-steroidal agents having equal efficacy. Furthermore, of the non-steroidal drugs, oral dapsone had greater efficacy than topical retinoid (p < 0.05). However, no significant differences in outcome were recorded for oral dapsone vs topical tacrolimus (p > 0.05) and for topical retinoid vs topical tacrolimus (p > 0.05).
Non-steroidal drugs such as dapsone, tacrolimus and retinoid are as efficacious as steroidal drugs for treating oral lichen planus, and avoid the side effects associated with steroids.
To evaluate the short- to medium-term effectiveness of potassium titanyl phosphate (KTP) laser Dermastat in patients with recurrent anterior epistaxis.
Fifty-eight patients presenting with recurrent anterior epistaxis were treated using potassium titanyl phosphate laser Dermastat. Those with recurrent epistaxis arising from prominent vessels in Little's area, and/or those for whom treatment with silver nitrate cautery failed, were included. The main outcome measure was resolution of epistaxis at two months.
Fifty-eight patients were treated; 27 were under 18 years old. Thirty patients had prominent vessels. Thirty-one patients had undergone previous cautery treatment. Thirty-eight patients had treatment to the left side, 19 to the right and 1 to both. At two months, 74 per cent reported resolution of epistaxis with no complications. This increased to 78 per cent at further follow up.
Our technique is a successful, safe treatment for recurrent anterior epistaxis in an otherwise treatment-resistant group. A single procedure is effective. The handpiece and tip are reusable and sterilisable, resulting in cost-effectiveness.
Introduction: Multiples barriers to appropriate analgesia are reported in the paediatric emergency department (PED), including limited accessibility to effective strategies. Our objective: was to evaluate the improvement in the accessibility of pain and anxiety management strategies in Canadian PEDs, after the creation of a national pediatric pain Quality Improvement Collaborative (QIC), through Pediatric Emergency Research Canada (PERC). Methods: In 2013, the TRAPPED 1 survey was administered to Canadian PEDs, in order to evaluate what resources were in place for pain and anxiety management. A pain QIC was then created to stimulate the implementation of new strategies, through information sharing between PEDs. In 2015, the TRAPPED 2 cross sectional survey was administered. Its focus was to evaluate the improvement in the accessibility of specific strategies reported by each centre, after participating in this QIC, and working to implement change within their own PEDs. Results: All 15/15 Canadian PEDs responded to the TRAPPED 1 survey in 2013 and 11 agreed to participate in the national pain QIC. In-person, phone meetings, follow up surveys and email communications were employed for information sharing. Strategies identified by the QIC to be newly introduced in individual centres were educational initiatives, distraction options, nurse-initiated protocols and intranasal (IN) medications. All 15 PEDs completed the TRAPPED 2 survey. Compared to 2013, an increased number of PEDs used face-based pain scales (14/15 vs 6/15) and behavioural scales (5/15 vs 1/15) for pain assessment in 2015. Use of reminder posters on pain management at triage increased from 4/15 to 6/15 PEDs. Availability of tablets for distraction increased from 4/15 to 10/15 PEDs. Nurse-initiated protocols for topical anesthetic and oral sucrose (for needle procedures) increased from 10/15 to 12/15 sites and from 12/15 to 14/15 sites respectively. Availability of IN medications increased; fentanyl from 9/15 to 14/15 sites and midazolam from 8/15 to 10/15 sites. Ten of the 11 PEDs involved in the QIC strategy reported the implementation of at least one of their own identified strategies. Conclusion: This study suggests that the use of a QIC may improve the introduction of new strategies to reduce pain and anxiety in EDs. QICs may also be helpful to other centres when introducing new strategies.
Expressed sequence tag-simple sequence repeat (EST-SSR) markers were used to analyse genetic diversity among three Lens species. The SSR loci amplified successfully in wild species, with 94·82% transferability in Lens culinaris subsp. orientalis, 95·4% in Lens nigricans, 98·81% in L. culinaris subsp. odemensis, 94·82% in L. culinaris subsp. tomentosus and 96·55% in Lens ervoides. Ninety-nine alleles (average 3·41 alleles/locus) were detected by 29 SSR markers. Based on the unweighted pair group method with arithmetic mean cluster analysis, all the genotypes were grouped into three clusters at a similarity level of 0·30. The diversity analysis indicated no species-specific clustering of the wild and cultivated species. Wild species L. nigricans and L. culinaris subsp. odemensis, L. culinaris subsp. orientalis and L. ervoides were grouped in Cluster I, whereas the Mediterranean land races of L. culinaris subsp. culinaris and L. culinaris subsp. tomentosus formed a separate group in Cluster II A. Cluster II B comprised L. ervoides, L. culinaris subsp. orientalis and L. culinaris subsp. culinaris. Clusters II C, II D and II F included cultivated Indian lentil genotypes. Cluster II E comprised Indian and Mediterranean germplasm lines. Cluster II F included three early maturing germplasm lines, whereas Cluster III included only two germplasm lines. The functional annotation of SSR-containing unigenes revealed that a majority of genes were involved in an important transport-related function or were a component of metabolic pathways. A high level of polymorphism of EST-SSRs and their transferability to related wild species indicated that these markers could be used for molecular screening, map construction, comparative genomic studies and marker-assisted selection.
As indicated by the sporadic Japanese encephalitis (JE) cases reported from the districts of Uttar Pradesh (UP), India, the disease is endemic in the state despite the fact that a JE vaccination programme has been ongoing in the state since 2006. Hence, the present study was undertaken to study the annual trend of JE in UP during January 2011 to December 2013. CSF and/or serum samples collected from acute encephalitis syndrome (AES) cases were referred to the virology laboratory at King George's Medical University, Lucknow and were tested for anti-JEV IgM antibodies by JEV MAC-ELISA kit. The study reveals that 26·9%, 9·9% and 14·8% of AES cases were positive for anti-JEV IgM in the years 2011, 2012 and 2013, respectively. Of the total JE confirmed cases, 30% were adults. Males were more commonly affected than females. A distinct peak of JE was seen in the monsoon and post-monsoon season, although sporadic cases were also reported in other months. JE vaccination by district in UP is discussed. This study reports that the proportion of JE positives in AES cases is decreasing in UP although the number of AES cases has not decreased. The study also discusses the probable causes of this decrease, including JE vaccination and natural periodicity due to herd immunity.
Forage sorghum is an important component of the fodder supply chain in the arid and semi-arid regions of the world because of its high productivity, ability to utilize water efficiently and adaptability to a wide range of climatic conditions. Identification of high-yielding stable genotypes (G) across environments (E) is challenging because of the complex G × E interactions (GEI). In the present study, the performance of 16 forage sorghum genotypes over seven locations across the rainy seasons of 2010 and 2011 was investigated using GGE biplot analysis. Analysis of variance revealed the existence of significant GEI for fodder yield and all eight associated phenotypic traits. Location accounted for a higher proportion of the variation (0·72–0·91), while genotype contributed only 0·06–0·21 of total variation in different traits. Genotype-by-location interactions contributed 0·02–0·13 of total variation. Promising genotypes for fodder yield and each of the associated traits could be identified effectively using a graphical biplot approach. The majority of test locations were highly correlated. A ‘Which-won-where’ study partitioned the test locations into two mega-environments (MEs): ME1 was represented by five locations with COFS 29 as the best genotype, while ME2 had two locations with S 541 as the best genotype. The existence of two MEs suggested a need for location-specific breeding. Genotype-by-trait biplots indicated that improvement for forage yield could be achieved through indirect selection for plant height, leaf number and early vigour.
Large amplitude ion-acoustic double layer (IADL) is studied using Sagdeev's pseudo-potential technique in collisionless unmagnetized plasma comprising hot and cold Maxwellian population of electrons, warm adiabatic ions, and dust grains. Variation of both Mach number (M) and amplitude |φm| of large amplitude IADL with charge, concentration, and mass of heavily charged massive dust grains is investigated for both positive and negative dust in plasma. Our numerical analysis shows that system supports only rarefactive large amplitude IADL for the selected set of plasma parameters. Our investigations for both negative and positive dust grains reveal that ion temperature increases the mobility of ions, resulting in increase in the Mach number of IADL. The larger mobility of ions causes leakage of ions from localized region, resulting into decrease in the amplitude of IADL. Other parameters, e.g. temperature ratio of hot to cold electrons, charge, concentration, mass of heavily charged massive dust grains also play significant role in the properties and existence of double layers. Since it is well established that both positive and negative dust are found in space as well as laboratory plasma, and double layers have a tremendous role to play in astrophysics, we have included both positive and negative dust in our numerical analysis for the study of large amplitude IADL. Further data used for negative dust are close to experimentally observed data. Hence, it is anticipated that our parametric studies for heavily charged (both positive and negative) dust may be useful in understanding laboratory plasma experiments, identifying nonlinear structures in upper part of ionosphere and lower part of magnetosphere structures, and in theoretical research for the study of properties of nonlinear structures.
The 2013 Infection Prevention and Control (IP&C) Guideline for Cystic Fibrosis (CF) was commissioned by the CF Foundation as an update of the 2003 Infection Control Guideline for CF. During the past decade, new knowledge and new challenges provided the following rationale to develop updated IP&C strategies for this unique population:
1. The need to integrate relevant recommendations from evidence-based guidelines published since 2003 into IP&C practices for CF. These included guidelines from the Centers for Disease Control and Prevention (CDC)/Healthcare Infection Control Practices Advisory Committee (HICPAC), the World Health Organization (WHO), and key professional societies, including the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA). During the past decade, new evidence has led to a renewed emphasis on source containment of potential pathogens and the role played by the contaminated healthcare environment in the transmission of infectious agents. Furthermore, an increased understanding of the importance of the application of implementation science, monitoring adherence, and feedback principles has been shown to increase the effectiveness of IP&C guideline recommendations.
2. Experience with emerging pathogens in the non-CF population has expanded our understanding of droplet transmission of respiratory pathogens and can inform IP&C strategies for CF. These pathogens include severe acute respiratory syndrome coronavirus and the 2009 influenza A H1N1. Lessons learned about preventing transmission of methicillin-resistant Staphylococcus aureus (MRSA) and multidrug-resistant gram-negative pathogens in non-CF patient populations also can inform IP&C strategies for CF.
A field experiment was carried out at the farm of Indian Agricultural Research Institute, New Delhi to quantify the effect of elevated carbon dioxide (CO2) and different levels of N fertiliser application on nitrous oxide (N2O) and carbon dioxide (CO2) emissions from soil under maize. The experiment included five treatments: 60 kg N ha−1 under ambient CO2 (385 ppm) in open plots, 120 kg N ha−1 under ambient CO2 (385 ppm) in open plots, 160 kg N ha−1 under ambient CO2 (385 ppm) in open plots, 120 kg N ha−1 under ambient CO2 (385 ppm) in open top chambers (OTC) and 120 kg N ha−1 under elevated CO2 (500 ± 50 ppm) in the OTC. Peaks of N2O flux were observed after every dose of N application. Cumulative N2O emission was 13% lower under ambient CO2 as compared to the elevated CO2 concentrations. There was an increase in CO2 emissions with application of N from 60 kg ha−1 to 160 kg ha−1. Higher yield and root biomass was observed under higher N treatment (160 kg N ha−1). There was no significant increase in maize yield under elevated CO2 as compared to ambient CO2. The carbon emitted was more than the carbon fixed under elevated CO2 as compared to ambient CO2 levels. The carbon efficiency ratio (C fixed/C emitted) was highest in ambient CO2 treatment in the OTC.
In this contribution, we report the synthesis and characterization of NixFe3-xO4 and CoxFe3-xO4 redox nanomaterials using sol-gel method. These materials will be used to produce solar fuels such as H2 or syngas from H2O and/or CO2 via solar thermochemical cycles (STCs). For the sol-gel synthesis of ferrites, the Ni, Co, Fe precursor salts were dissolved in ethanol and propylene oxide (PO) was added dropwise to the well mixed solution as a gelation agent to achieve gel formation. Freshly synthesized gels were aged, dried, and calcined by heating them to 600°C in air. The calcined powders were characterized by powder x-ray diffractometer (XRD), BET surface area, as well as scanning (SEM) and transmission (TEM) electron microscopy. Their suitability to be used in STCs for the production of solar fuels was assessed by performing several reduction/re-oxidation cycles using a thermogravimetric analyzer (TGA).
We have been developing a collection of low-cost experiments for exploring the science of glassy materials through hands-on activities with sucrose based glass (a.k.a. hard candy). These form a mini-curriculum of glass science, consisting of inter-related experiments and home built apparatuses. It provides an environment to develop an understanding of glassy materials through active, prolonged engagement. Some of our earlier experiments were reported four years ago. Since that report we have made substantial improvements and added new topics, including electrical and thermal conductivity, an improved DTA apparatus, and improved methodology for crystallization kinetics. All of our experiments are designed to be low-cost (typically <$100) and the apparatuses are designed for construction by students or teachers.