Global communication part 1: the use of apparel CAD technology

Trends needed for improved communication systems, through the development of future computer-aided design technology (CAD) applications, is a theme that has received attention due to its perceived benefits in improving global supply chain efficiencies. This article discusses the developments of both 2D and 3D computer-aided design capabilities, found within global fashion supply chain relationships and environments. Major characteristics identified within the data suggest that CAD/CAM technology appears to be improving; however, evidence also suggest a plateau effect, which is accrediting forced profits towards information technology manufactures, and arguably compromising the industry's competitive advantage. Nevertheless, 2D CAD increases communication speed; whereas 3D human interaction technology is seen to be evolving slowly and questionably with limited success. The article discusses the findings and also presents the issues regarding human interaction; technology education; and individual communication enhancements using technology processes. These are still prevalent topics for the future developments of global strategy and cultural communication amalgamation

Cognitive and behavioural strategies employed to overcome "lapses" and prevent "relapse" among weight-loss maintainers and regainers: A qualitative study.

While many behavioural weight management programmes are effective in the short-term, post-programme weight regain is common. Overcoming "lapses" and preventing "relapse" has been highlighted as important in weight-loss maintenance, but little is known on how this is achieved. This study aimed to compare the cognitive and behavioural strategies employed to overcome "lapses" and prevent "relapse" by people who had regained weight or maintained weight-loss after participating in a weight management programme. By investigating differences between groups, we intended to identify strategies associated with better weight-loss maintenance. Semi-structured interviews were conducted with 26 participants (58% female) recruited from the 5-year follow-up of the Weight Loss Referrals for Adults in Primary Care (WRAP) trial (evaluation of a commercial weight-loss programme). Participants who had lost ≥5% baseline weight during the active intervention were purposively sampled according to 5-year weight trajectories (n = 16 'Regainers', n = 10 'Maintainers'). Interviews were audio-recorded, transcribed verbatim, and analysed thematically. Key differences in strategies were that Maintainers continued to pay attention to their dietary intake, anticipated and planned for potential lapses in high-risk situations, and managed impulses using distraction techniques. Regainers did not report making plans, used relaxed dietary monitoring, found distraction techniques to be ineffective and appeared to have difficulty navigating food within interpersonal relationships. This study is one of the longest qualitative follow-ups of a weight loss trial to date, offering unique insights into long-term maintenance. Future programmes should emphasize strategies focusing on self-monitoring, planning and managing interpersonal relationships to help participants successfully maintain weight-loss in the longer-term.This study is funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research RP-PG-0216-20010. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. ALA and SJG are supported by the Medical Research Council (MC_UU_12015/4). SJG is an NIHR senior investigator. The University of Cambridge has received salary support in respect of SJG from the National Health Service in the East of England through the Clinical Academic Reserve

Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs

Livestock diseases caused by Trypanosoma congolense, T. vivax and T. brucei, collectively known as nagana, are responsible for billions of dollars in lost food production annually. There is an urgent need for novel therapeutics. Encouragingly, promising antitrypanosomal benzoxaboroles are under veterinary development. Here, we show that the most efficacious subclass of these compounds are prodrugs activated by trypanosome serine carboxypeptidases (CBPs). Drug-resistance to a development candidate, AN11736, emerged readily in T. brucei, due to partial deletion within the locus containing three tandem copies of the CBP genes. T. congolense parasites, which possess a larger array of related CBPs, also developed resistance to AN11736 through deletion within the locus. A genome-scale screen in T. brucei confirmed CBP loss-of-function as the primary mechanism of resistance and CRISPR-Cas9 editing proved that partial deletion within the locus was sufficient to confer resistance. CBP re-expression in either T. brucei or T. congolense AN11736-resistant lines restored drug-susceptibility. CBPs act by cleaving the benzoxaborole AN11736 to a carboxylic acid derivative, revealing a prodrug activation mechanism. Loss of CBP activity results in massive reduction in net uptake of AN11736, indicating that entry is facilitated by the concentration gradient created by prodrug metabolism.</p

Smoke gets in your eyes: re-reading gender in the "nostalgia film"

Upon its release, American Graffiti (George Lucas, 1973) was much admired by critics and audiences alike. Yet, in subsequent years, the film became known for its supposed “flattening of history,” and celebration of patriarchal values. This article demonstrates that such a judgement owes much to Fredric Jameson’s historically contingent work on postmodernism, which argues that American Graffiti constitutes the paradigmatic nostalgia film. In contrast, using close textual analysis, I demonstrate that American Graffiti provides a more complex construction of the past, and of gender, than has hitherto been acknowledged. Far from blindly idealising the early 1960s, the film interrogates the processes through which the period and its gender relations come to be idealised. This article has consequences not only for our understanding of Lucas’ seminal film, but also for the American New Wave, and the “nostalgia” text

Deletion of transketolase triggers a stringent metabolic response in promastigotes and loss of virulence in amastigotes of Leishmania mexicana

Transketolase (TKT) is part of the non-oxidative branch of the pentose phosphate pathway (PPP). Here we describe the impact of removing this enzyme from the pathogenic protozoan Leishmania mexicana. Whereas the deletion had no obvious effect on cultured promastigote forms of the parasite, the Δtkt cells were not infective to mice. Δtkt promastigotes were more susceptible to oxidative stress and various leishmanicidal drugs than wild-type, and metabolomics analysis revealed profound changes to metabolism in these cells. In addition to changes consistent with those directly related to the role of TKT in the PPP, central carbon metabolism was substantially decreased, the cells consumed significantly less glucose, flux through glycolysis diminished, and production of the main end products of metabolism was decreased. Only minor changes in RNA abundance from genes encoding enzymes in central carbon metabolism, however, were detected although fructose-1,6-bisphosphate aldolase activity was decreased two-fold in the knock-out cell line. We also showed that the dual localisation of TKT between cytosol and glycosomes is determined by the C-terminus of the enzyme and by engineering different variants of the enzyme we could alter its sub-cellular localisation. However, no effect on the overall flux of glucose was noted irrespective of whether the enzyme was found uniquely in either compartment, or in both

Investigation of rheumatoid arthritis susceptibility loci in juvenile idiopathic arthritis confirms high degree of overlap

&lt;p&gt;Objectives: Rheumatoid arthritis (RA) shares some similar clinical and pathological features with juvenile idiopathic arthritis (JIA); indeed, the strategy of investigating whether RA susceptibility loci also confer susceptibility to JIA has already proved highly successful in identifying novel JIA loci. A plethora of newly validated RA loci has been reported in the past year. Therefore, the aim of this study was to investigate these single nucleotide polymorphisms (SNP) to determine if they were also associated with JIA.&lt;/p&gt; &lt;p&gt;Methods: Thirty-four SNP that showed validated association with RA and had not been investigated previously in the UK JIA cohort were genotyped in JIA cases (n=1242), healthy controls (n=4281), and data were extracted for approximately 5380 UK Caucasian controls from the Wellcome Trust Case–Control Consortium 2. Genotype and allele frequencies were compared between cases with JIA and controls using PLINK. A replication cohort of 813 JIA cases and 3058 controls from the USA was available for validation of any significant findings.&lt;/p&gt; &lt;p&gt;Results: Thirteen SNP showed significant association (p&#60;0.05) with JIA and for all but one the direction of association was the same as in RA. Of the eight loci that were tested, three showed significant association in the US cohort.&lt;/p&gt; &lt;p&gt;Conclusions: A novel JIA susceptibility locus was identified, CD247, which represents another JIA susceptibility gene whose protein product is important in T-cell activation and signalling. The authors have also confirmed association of the PTPN2 and IL2RA genes with JIA, both reaching genome-wide significance in the combined analysis.&lt;/p&gt

Speaking in a second language but thinking in the first language: Language-specific effects on memory for causation events in English and Spanish

Aims and objectives/purpose/research question: This paper’s objective is to offer new insights into the effects of language on memory for causation events in a second language (L2) context. The research was driven by the question of whether proficient L2 users acquired L2 thinking-for-speaking-and-remembering strategies along with the relevant expressions for different types of causation (intentional versus non-intentional). Design/methodology/approach: The cognitive domain of causation is an ideal platform for this investigation, since the lexicalisation of causation differs clearly in the two languages under consideration, English and Spanish. Spanish speakers always distinguish between intentional and non-intentional events through the use of different constructions. The English pattern of lexicalisation in this domain often leaves intentionality unspecified. Our methodology involves an experimental elicitation of event verbalisations and recall memory responses to video stimuli by English and Spanish monolinguals and bilinguals. Data and analysis: The analysis has shown that the Spanish monolinguals and first language (L1) Spanish/L2 English speakers always distinguished between intentional and non-intentional events, while the English monolinguals and L1 English/L2 Spanish speakers generally used expressions that were underspecified with regard to intentionality. Findings/conclusions: All populations used their habitual language patterns as an aid to memory. Spanish monolingual had better recall than their English peers. L2 speakers were mainly relying on the L1 in spite of speaking only the L2 during the experiment. Originality: Possible effects of these typological differences between an L1 and an L2 on speaker recall memory have not been investigated before. Significance/implications: The research presented in this paper informs the theoretical assumptions related to the thinking-for-speaking hypothesis by showing empirically that late bilinguals adhere to their L1 patterns as an aid to memory while speaking in their L2. This novel finding contributes to an improved understanding of language processing and language use among late bilinguals

Sterol 14α-demethylase mutation leads to amphotericin B resistance in Leishmania mexicana

Amphotericin B has emerged as the therapy of choice for use against the leishmaniases. Administration of the drug in its liposomal formulation as a single injection is being promoted in a campaign to bring the leishmaniases under control. Understanding the risks and mechanisms of resistance is therefore of great importance. Here we select amphotericin B-resistant Leishmania mexicana parasites with relative ease. Metabolomic analysis demonstrated that ergosterol, the sterol known to bind the drug, is prevalent in wild-type cells, but diminished in the resistant line, where alternative sterols become prevalent. This indicates that the resistance phenotype is related to loss of drug binding. Comparing sequences of the parasites’ genomes revealed a plethora of single nucleotide polymorphisms that distinguish wild-type and resistant cells, but only one of these was found to be homozygous and associated with a gene encoding an enzyme in the sterol biosynthetic pathway, sterol 14α-demethylase (CYP51). The mutation, N176I, is found outside of the enzyme’s active site, consistent with the fact that the resistant line continues to produce the enzyme’s product. Expression of wild-type sterol 14α-demethylase in the resistant cells caused reversion to drug sensitivity and a restoration of ergosterol synthesis, showing that the mutation is indeed responsible for resistance. The amphotericin B resistant parasites become hypersensitive to pentamidine and also agents that induce oxidative stress. This work reveals the power of combining polyomics approaches, to discover the mechanism underlying drug resistance as well as offering novel insights into the selection of resistance to amphotericin B itself

European Academy of Neurology and European Stroke Organization consensus statement and practical guidance for pre-hospital management of stroke

Background and purposeThe reduction of delay between onset and hospital arrival and adequate pre-hospital care of persons with acute stroke are important for improving the chances of a favourable outcome. The objective is to recommend evidence-based practices for the management of patients with suspected stroke in the pre-hospital setting. MethodsThe GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to define the key clinical questions. An expert panel then reviewed the literature, established the quality of the evidence, and made recommendations. ResultsDespite very low quality of evidence educational campaigns to increase the awareness of immediately calling emergency medical services are strongly recommended. Moderate quality evidence was found to support strong recommendations for the training of emergency medical personnel in recognizing the symptoms of a stroke and in implementation of a pre-hospital code stroke' including highest priority dispatch, pre-hospital notification and rapid transfer to the closest stroke-ready' centre. Insufficient evidence was found to recommend a pre-hospital stroke scale to predict large vessel occlusion. Despite the very low quality of evidence, restoring normoxia in patients with hypoxia is recommended, and blood pressure lowering drugs and treating hyperglycaemia with insulin should be avoided. There is insufficient evidence to recommend the routine use of mobile stroke units delivering intravenous thrombolysis at the scene. Because only feasibility studies have been reported, no recommendations can be provided for pre-hospital telemedicine during ambulance transport. ConclusionsThese guidelines inform on the contemporary approach to patients with suspected stroke in the pre-hospital setting. Further studies, preferably randomized controlled trials, are required to examine the impact of particular interventions on quality parameters and outcome. Click for the corresponding questions to this CME article