Search

Background: Sequence alignment lies at the heart of genome sequence annotation. While the BLAST suite of alignment tools has long held an important role in alignment-based sequence database search, greater sensitivity is achieved through the use of profile hidden Markov models (pHMMs). Here, we describe an FPGA hardware accelerator, called HAVAC, that targets a key bottleneck step (SSV) in the analysis pipeline of the popular pHMM alignment tool, HMMER. Results: The HAVAC kernel calculates the SSV matrix at 1739 GCUPS on a ∼ $3000 Xilinx Alveo U50 FPGA accelerator card, ∼ 227× faster than the optimized SSV implementation in nhmmer. Accounting for PCI-e data transfer data processing, HAVAC is 65× faster than nhmmer's SSV with one thread and 35× faster than nhmmer with four threads, and uses ∼ 31% the energy of a traditional high end Intel CPU. Conclusions: HAVAC demonstrates the potential offered by FPGA hardware accelerators to produce dramatic speed gains in sequence annotation and related bioinformatics applications. Because these computations are performed on a co-processor, the host CPU remains free to simultaneously compute other aspects of the analysis pipeline. [ABSTRACT FROM AUTHOR]

Therefore, it would seem that the appropriate description of the upper lid movement in the patient reported by Ordás et al[1] is lid myorhythmia rather than lid nystagmus. Interestingly, this can be maximal with the lids lightly or incompletely closed.[6] In each of these three types of lid nystagmus there is a rapid upward movement of the lid followed by a slower downward restoration of the lid position. In this issue, Ordás and colleagues[1] report a case of "eyelid nystagmus" in a 75-year-old woman presenting with 5 years progressive gait disorder on a background of hypertension. [Extracted from the article]

The article discusses that economic liberal theory, created in particular historical circumstances to serve powerful interests, has been used by the nominally liberal Anglo-American hegemonic project. Neoliberal ideology is understood as a synthesis of hegemonic strategy with asymmetric economic liberal practice. It mentions the historical context of economic liberal mythology, the broader history of Anglo-American liberal ideas and institutions, and the de-liberalisation of the project.

Background: Pattern matching is a key step in a variety of biological sequence analysis pipelines. The FM-index is a compressed data structure for pattern matching, with search run time that is independent of the length of the database text. Implementation of the FM-index is reasonably complicated, so that increased adoption will be aided by the availability of a fast and flexible FM-index library. Results: We present AvxWindowedFMindex (AWFM-index), a lightweight, open-source, thread-parallel FM-index library written in C that is optimized for indexing nucleotide and amino acid sequences. AWFM-index introduces a new approach to storing FM-index data in a strided bit-vector format that enables extremely efficient computation of the FM-index occurrence function via AVX2 bitwise instructions, and combines this with optional on-disk storage of the index's suffix array and a cache-efficient lookup table for partial k-mer searches. The AWFM-index performs exact match count and locate queries faster than SeqAn3's FM-index implementation across a range of comparable memory footprints. When optimized for speed, AWFM-index is ∼ 2–4x faster than SeqAn3 for nucleotide search, and ∼ 2–6x faster for amino acid search; it is also ∼ 4x faster with similar memory footprint when storing the suffix array in on-disk SSD storage. Conclusions: AWFM-index is easy to incorporate into bioinformatics software, offers run-time performance parameterization, and provides clients with FM-index functionality at both a high-level (count or locate all instances of a query string) and low-level (step-wise control of the FM-index backward-search process). The open-source library is available for download at https://github.com/TravisWheelerLab/AvxWindowFmIndex. [ABSTRACT FROM AUTHOR]

Background: Pattern matching is a key step in a variety of biological sequence analysis pipelines. The FM-index is a compressed data structure for pattern matching, with search run time that is independent of the length of the database text. Implementation of the FM-index is reasonably complicated, so that increased adoption will be aided by the availability of a fast and flexible FM-index library. Results: We present AvxWindowedFMindex (AWFM-index), a lightweight, open-source, thread-parallel FM-index library written in C that is optimized for indexing nucleotide and amino acid sequences. AWFM-index introduces a new approach to storing FM-index data in a strided bit-vector format that enables extremely efficient computation of the FM-index occurrence function via AVX2 bitwise instructions, and combines this with optional on-disk storage of the index's suffix array and a cache-efficient lookup table for partial k-mer searches. The AWFM-index performs exact match count and locate queries faster than SeqAn3's FM-index implementation across a range of comparable memory footprints. When optimized for speed, AWFM-index is ∼ 2–4x faster than SeqAn3 for nucleotide search, and ∼ 2–6x faster for amino acid search; it is also ∼ 4x faster with similar memory footprint when storing the suffix array in on-disk SSD storage. Conclusions: AWFM-index is easy to incorporate into bioinformatics software, offers run-time performance parameterization, and provides clients with FM-index functionality at both a high-level (count or locate all instances of a query string) and low-level (step-wise control of the FM-index backward-search process). The open-source library is available for download at https://github.com/TravisWheelerLab/AvxWindowFmIndex. [ABSTRACT FROM AUTHOR]

This paper builds on our recent work (Anderson et al., 2020; Anderson & Okuda, 2019 ; Anderson et al., 2021) investigating macrostructural variation in doctoral dissertations. Two of the central questions that remained under-addressed in this (and other) prior research were if and how dissertation macrostructures have changed over time, and what this change might indicate in terms of acceptable and preferred dissertation writing practices and the personal choices and institutional forces that shape dissertation genres. To address this, our present study includes a corpus of 1,254 doctoral dissertations from a single Canadian research university spanning a 52-year period from 1966 to 2018. As a related question, we were also curious about the proclivity of co-authorship practices in dissertation texts, since previous research (Anderson et al., 2021) has demonstrated that co-authorship is common with certain dissertation macrostructures but much less so (or even non-existent) in others. As shown below, both macrostructures and co-authorship demonstrated changes over time in the corpus of texts analyzed for this study. Dissertations are now increasingly manuscript-based and/or contain published sections, many of these co-authored. The authors conclude with implications of this change and calls for further inquiry in this area. • We analyzed 1254 doctoral dissertations for macrostructure and authorship practices. • 52 years of education dissertations were analyzed from one research university. • Both macrostructure and (co)authorship practices have changed over time. • "Alternative" dissertation macrostructures are now as popular as traditional ones. • Co-authorship is common in some macrostructures and non-existent in others. [ABSTRACT FROM AUTHOR]

Postsecondary institutions in the global north have rapidly internationalized, driven mainly by the proliferation of international students and responses to these changing demographics. This internationalization has captured attention across various platforms, including increased media focus directed toward these students and the primary and ancillary influences of their participation in PSIs and surrounding communities. The project explored in this paper examines this phenomenon by connecting internationalization of higher education research with insights from critical media studies and framing theory to investigate news media representations of international and refugee students' participation in Canadian universities and colleges. A critical thematic analysis was performed on 391 news media texts published between 2000 and 2017. Findings reveal the Canadian news media's tendency to construct issues related to international students and internationalization into one or a combination of four broad macrothemes: (1) Canada as benevolent and ideal; (2) international students and internationalization as commodified assets; (3) international students and internationalization as threats; and (4) the strategic neutrality of data. [ABSTRACT FROM AUTHOR]

Intersections between transnationalism, the internationalization of higher education, and applied linguistics continue to draw attention, as the proliferation of academic mobility is increasingly influencing students, instructors, and universities globally. As one of the world's major receiving countries of international postsecondary students, Canada, and its universities, has been similarly impacted. This article presents two informative and contrastive perspectives based on the experiences of two Chinese doctoral students at a large Canadian university. I focus particularly on the students' national and transnational ideologies, identities, and future outlooks, and how these formative experiences and positionalities shaped their perspectives, goals, and motivations during their study abroad. This research demonstrates how the (transnational) identities of these two students were discursively and iteratively formed based on complex intersections of national and transnational discourses regarding the representations of overseas returnees and the students' conceptions and co-constructions of the legitimate academic transnational and home. These discursive constructions and enactments in turn had an influential effect on their challenges, desires, and abilities to integrate into local academic discourses and communities. [ABSTRACT FROM AUTHOR]

Abstract: We compared biochemical, functional, and behavioral responses to the organophosphorus anticholinesterase chlorpyrifos oxon (CPO) in mice (Mus musculus, CD‐1) and toads (Anaxyrus cognatus, Great Plains toad). Toads were substantially less sensitive to acute lethality of CPO based on the maximum tolerated (nonlethal) dose (toads, 77 mg/kg; mice, 5.9 mg/kg). Sublethal exposures led to classical signs of toxicity (increased involuntary movements, autonomic secretions) in mice but hypoactivity in toads. Motor performance in an inclined plane test was not affected by CPO in mice but was altered at the highest dosage in toads. Acetylcholinesterase (AChE), butyrylcholinesterase, monoacylglycerol lipase, and fatty acid amide hydrolase activities in brain were inhibited in mice but not in toads, and fatty acid amide hydrolase activity in the liver was inhibited in both species. Toad brain AChE was less sensitive to in vitro inhibition by CPO (50% inhibitory concentration [IC50; 20 min, 37 °C], 101 vs 7.8 nM; IC50 [20 min, 26 °C], 149 vs 6.2 nM), and studies of inhibitor kinetics indicated substantially lower anticholinesterase potency of CPO against the toad brain enzyme. Using an in vitro indirect inhibition assay, preincubation of CPO with toad brain homogenate was more effective than an equivalent mouse brain homogenate at reducing CPO potency. These data suggest that the relatively low sensitivity of toads to cholinergic toxicity is based on the low sensitivity of brain AChE, which in turn may be attributable to more effective target‐site detoxification. Environ Toxicol Chem 2018;37:1898–1906. © 2018 SETAC [ABSTRACT FROM AUTHOR]

The Ag-Cu-In thermodynamic material system is of interest for brazing alloys and chalcopyrite thin-film photovoltaics. To advance these applications, Ag-Cu-In was assessed and a Calphad model was developed. Binary Ag-Cu and Cu-In parameters were taken from previous assessments, while Ag-In was re-assessed. Structure-based models were employed for β-bcc(A2)-Ag3In, γ-Ag9In4, and AgIn2 to obtain good fit to enthalpy, phase boundary, and invariant reaction data for Ag-In. Ternary Ag-Cu-In parameters were optimized to achieve excellent fit to activity, enthalpy, and extensive phase equilibrium data. Relative to the previous Ag-Cu-In assessment, fit was improved while fewer parameters were used. [ABSTRACT FROM AUTHOR]

Incorporation of K has led to world record Cu(In,Ga)Se 2 photovoltaic power conversion efficiencies, but there is poor consensus about the role of phase impurities in these advances. This work lays a foundation for identifying and controlling these phase impurities. Films of Cu-K-In-Se were co-evaporated at varied K/(K + Cu) compositions and substrate temperatures (with constant (K + Cu)/In ∼ 0.85). Increased Na composition on the substrate's surface and decreased growth temperature were both found to favor Cu 1-x K x InSe 2 alloy formation, relative to two-phase CuInSe 2 +KInSe 2 formation. Structures from X-ray diffraction (XRD), band gaps, resistivities, minority carrier lifetimes and carrier concentrations from time-resolved photoluminescence were in agreement with previous reports, where low K/(K + Cu) composition films exhibited properties promising for photovoltaic absorbers. Films grown at 400–500 °C were then annealed to 600 °C in a controlled Se ambient, which caused K loss by evaporation in proportion to the initial K/(K + Cu) composition. Similar to growth temperature, annealing drove Cu 1-x K x InSe 2 alloy consumption and CuInSe 2 +KInSe 2 production, as evidenced by high temperature XRD. Annealing also decomposed KInSe 2 and formed K 2 In 12 Se 19 . At high temperature, the KInSe 2 crystal lattice gradually contracted as temperature and time increased, as well as just time. Evaporative loss of K during annealing could accompany the generation of vacancies on K lattice sites, and may explain the KInSe 2 lattice contraction. This knowledge of Cu-K-In-Se material chemistry may be used to predict and control minor phase impurities in Cu(In,Ga)(Se,S) 2 photovoltaic absorbers—where impurities below typical detection limits may have played a role in recent world record photovoltaic efficiencies that utilized KF post-deposition treatments. [ABSTRACT FROM AUTHOR]

This article examines the internal and external academic discourse socialization of seven Chinese PhD students at a large Canadian university. Through the use of interviews, participant-generated written narratives, and discussion of written feedback, this longitudinal multiple case study uncovered multiple and complex factors facilitating students’ socialization into local practices, discourses, and communities during their doctoral study. This article highlights the disciplinary role of internal and external socialization in mediating behaviours, affective stances, and (in)action, a process referred to as the doctoral gaze, conceptually drawn from Foucault's (1995) notion of panopticism. Students’ self- and other-mediated and directed forms of socialization comprised a recursive process where they learned to do being PhD students through the use of internal and external sources and resources. Their relative abilities to become active agents in the process, and effectively self- and other-socialize into practices, behaviours, and positionalities conducive to success, were key aspects in the broader socialization process. [ABSTRACT FROM AUTHOR]

While this article makes explicit connections with forms such as karaoke, it also offers insight into other areas of sonic instruction such as dance, exercise and gaming. More important, it begins to develop an explicit theoretical foothold on questions of record production and reception where the listener is conceived in both the form of the recording and its accompanying narratives by focusing on how many of these instructional objects are designed around specific questions of record production and their accompanying paratextual elements. [ABSTRACT FROM AUTHOR]

Feelings of shame are normal when suffering guilt from sin, but the church too often gives congregants a simplistic "shame script," which paints God only as an angry or disappointed judge and so circumvents a lasting relational intimacy with him. For those who struggle to approach God because of the shame they suffer from past sins and current temptations, recent psychological research provides some insight. I demonstrate: those who agonize over feelings of shame need new "cultural scripts" and "life scripts" by which to flourish, new narratives wherein a healthier view of God, self and community might emerge. The starting point is a proper biblical script of God as our Father, a vision of God the Father that resists one-dimensional notions of divine anger and disappointment. A more robust, intimate and grace-filled concept of God the Father, in other words, provides relief to the sufferers of unhealthy shame. [ABSTRACT FROM AUTHOR]

The article compares economic reform in Cuba and Ecuador. Topics covered include the misconceptions about the reform processes, the historical legacies that Cuba and Ecuador share, and the contribution of Fidel Castro, the chief architect of the Cuban Revolution, to reforms in Cuba. Also discussed are the role of Movimiento Patria Altiva y Soberana (PAIS) group led by Rafael Correa in Ecuador's reform, and how economic reform is understood across cultures.

The article discusses issues concerning the plan of Australia and Cuba to collaborate in health aid programs in the Pacific, Timor Leste and Caribbean regions as of July 2014. Topics covered include the encounter of former Australian Foreign Minister Stephen Smith with Bruno Rodriguez, foreign minister of Cuba, in 2010 to discuss the plan to cooperate in health assistance, the concept of modified neoliberal system, and the doctor-centred public system of Cuba.

The article discusses the challenges in the proposed partnership between Australia and Cuba in such fields as health aid programs in the Pacific and Caribbean regions as of January 2014. It claims that such collaboration was first advanced by the Labor government and is expected to be continued by the conservative government. Other issues discussed include how to deal with language and syllabus differences in the training of health workers and the state of health care in both countries.

The author discusses the effect of changes to music distribution in the 21st century on the job description and prestige of television music supervisors such as Alexandra Patsavas, who started the music label Chop Shop after her success working on the show "The O.C." Revenue for bands from film and television licensing, U.S. music publishing, and branding are discussed, as well as music industry workers such as supervisor Maureen Crowe, label executive Gil Goldberg, and rock band Bon Jovi.

The neural pathways and brain regions involved in eye movements during ocular fixation and gaze control include the cerebrum, brainstem and cerebellum, and abnormal eye movements can indicate the presence of neurodegeneration. In some patients, oculomotor signs are key to making a diagnosis. Careful clinical examination of eye movements in patients with neurodegenerative disorders is, therefore, an invaluable adjunct to neurological and cognitive assessments. Eye movement recordings in the laboratory are generally not necessary for diagnostic purposes, but can be a useful addition to the clinical examination. Laboratory recordings of eye movements can provide valuable information about disease severity, progression or regression in neurodegenerative disease, and hold particular promise for objective evaluation of the efficacy of putative neuroprotective and neurorestorative therapies. For example, aspects of saccade performance can be tested to probe both motor and cognitive aspects of oculomotor behaviour. This Review describes the oculomotor features of the major age-related movement disorders, including Parkinson disease, Huntington disease, dementia and other neurodegenerative disorders. Findings in presymptomatic individuals and changes associated with disease progression are discussed. [ABSTRACT FROM AUTHOR]

The article explains the impact of formal markets and modernization in Melanesia, particularly on Papua New Guinea. The historical development of land modernization in the region is presented including the livelihood opportunities for Melanesian families. The benefits of modernization of natives' lands include an increase in formal economies and access to rural credit. Sources of arguments for formal land markets consists of international aid agencies and some government officials.

Purpose: Up to 90% of people with Parkinson's disease (PD) develop communication difficulties over the course of the disease. While the negative effect of dysarthria on communicative participation has been well-documented, the impact of the occurrence of acquired stuttered disfluencies on communication in different speech situations is unknown. This study aimed to determine if the frequency of occurrence of stuttered disfluencies affects communicative participation in individuals with PD, and whether such a relationship is mediated by examiner- and self-rated measures of disease severity. Method: Conversational speech samples were collected from 100 people with PD aged 53-91 years to calculate the frequency of occurrence of stuttered disfluencies. Participants completed the Communicative Participation Item Bank to assess participation in communicative situations. Information on overall speech, cognitive, and motor performance was collected using both self-rated and examiner-rated methods. Results: Participants with PD presented with 0.2%-9.9% stuttered disfluencies during conversation. Overall, participants with PD reported their communicative participation to be impacted "a little" (19.5 ± 7.0), but there was considerable interindividual variation. A higher frequency of stuttered disfluencies was associated with significantly lower communicative participation (1 = -0.32, p < .01). In addition, examiner-rated frequency of stuttered disfluencies (p < .01), speech (p < .01), and motor severity (p = .04) were all significant predictors of communicative participation. Using self-ratings, speech (p < .01) and cognitive (p < .01) measures significantly predicted communicative participation. Conclusions: In people with PD, communicative participation was significantly worse for those with a higher frequency of stuttered disfluencies. Examiner- and self-rated measures of disease severity contributed different information related to communicative constraints. Together, these results highlight the importance of individualized and holistic speech therapy that considers a wide variety of symptoms, including stuttered disfluencies, to ensure positive functional outcomes. [ABSTRACT FROM AUTHOR]

Cognitive impairment is a well‐recognized and debilitating symptom of Parkinson's disease (PD). Degradation in the cortical cholinergic system is thought to be a key contributor. Both postmortem and in vivo cholinergic positron emission tomography (PET) studies have provided valuable evidence of cholinergic system changes in PD, which are pronounced in PD dementia (PDD). A growing body of literature has employed magnetic resonance imaging (MRI), a noninvasive, more cost‐effective alternative to PET, to examine cholinergic system structural changes in PD. This review provides a comprehensive discussion of the methodologies and findings of studies that have focused on the relationship between cholinergic basal forebrain (cBF) integrity, based on T1‐ and diffusion‐weighted MRI, and cognitive function in PD. Nucleus basalis of Meynert (Ch4) volume has been consistently reduced in cognitively impaired PD samples and has shown potential utility as a prognostic indicator for future cognitive decline. However, the extent of structural changes in Ch4, especially in early stages of cognitive decline in PD, remains unclear. In addition, evidence for structural change in anterior cBF regions in PD has not been well established. This review underscores the importance of continued cross‐sectional and longitudinal research to elucidate the role of cholinergic dysfunction in the cognitive manifestations of PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Select cultivated meat (CM) products have been approved for sale and consumption in Singapore, the USA, and Israel. Palatability, a term encompassing the taste, texture, and aroma of foods, plays a central role in the appeal of foods. Currently, the consumer appeal of CM is relatively low, including low perceptions of palatability and a variable willingness to try. The palatability of meat arises from the unique chemistry and structure of its cellular constituents: muscle, fat, and stroma. Natural post-mortem processes, deliberate post-processing modifications, and various cooking methods are crucial in determining the palatability of agricultural meat (AM); replicating these processes could improve the palatability of CM. Cultivated meat (CM) has transitioned from a futuristic concept to a present reality, with select products approved for consumption and sale in Singapore, Israel, and the USA. This evolution has emphasized scalable, cost-effective, and sustainable production, as well as navigation of regulatory pathways. As CM develops, a crucial challenge lies in delivering products that are highly appealing to consumers. Central to this will be refining CM palatability, a term encompassing food's taste, aroma, texture, tenderness, juiciness, and color. We explore the scientific and engineering approaches to producing palatable CM, including cell-line selection, cell differentiation, and post-processing techniques. This includes a discussion of the structural and compositional properties of meat that are intrinsically coupled to palatability. [ABSTRACT FROM AUTHOR]

Malaria parasites vary in phenotypic traits of biomedical or biological interest such as growth rate, virulence, sex ratio and drug resistance, and there is considerable interest in identifying the genes that underlie this variation. An important first step is to determine trait heritability (H²). We evaluate two approaches to measuring H² in natural parasite populations using relatedness inferred from genetic marker data. We collected single-clone Plasmodium falciparum infections from 185 patients from the Thailand-Burma border, monitored parasite clearance following treatment with artemisinin combination therapy (ACT), measured resistance to six antimalarial drugs and genotyped parasites using 335 microsatellites. We found strong relatedness structure. There were 27 groups of two to eight clonally identical (CI) parasites, and 74 per cent of parasites showed significant relatedness to one or more other parasites. Initially, we used matrices of allele sharing and variance components (VC) methods to estimate H². Inhibitory concentrations (IC50) for six drugs showed significant H² (0.24 to 0.79, p = 0.06 to 2.85 × 10-9), demonstrating that this study design has adequate power. However, a phenotype of current interest--parasite clearance following ACT--showed no detectable heritability (H² =0-0.09, ns) in this population. The existence of CI parasites allows the use of a simple ANOVA approach for quantifying H², analogous to that used in human twin studies. This gave similar results to the VC method and requires considerably less genotyping information. We conclude (i) that H² can be effectively measured in malaria parasite populations using minimal genotype data, allowing rational design of genome-wide association studies; and (ii) while drug response (IC50) shows significant H², parasite clearance following ACT was not heritable in the population studied. [ABSTRACT FROM AUTHOR]

This article focuses on the specific aesthetic formation resulting after the reorganization of the FM segment of the electromagnetic spectrum in the American post-WWII period of the late 1940s and 1950s. FM's distinction in this period was as an emergent alternative space that promoted itself with a rhetoric that emphasized the medium as a more democratic, less commercial mode of communication and musical exhibition. This article looks at a combination of programming guides, trade press and general press sources to understand how this rhetoric manifested itself through programming, ownership, FM audiences and their aesthetic expectations that influenced the development of the much heralded American FM freeform radio formats throughout the 1960s and 1970s. [ABSTRACT FROM AUTHOR]

Alteration in gene copy number provides a simple way to change expression levels and alter phenotype. This was fully appreciated by bacteriologists more than 25 years ago, but the extent and implications of copy number polymorphism (CNP) have only recently become apparent in other organisms. New methods demonstrate the ubiquity of CNPs in eukaryotes and their medical importance in humans. CNP is also widespread in the Plasmodium falciparum genome and has an important and underappreciated role in determining phenotype. In this review, we summarize the distribution of CNP, its evolutionary dynamics within populations, its functional importance and its mode of evolution. [Copyright &y& Elsevier]

Cuba presenta la tasa más baja de infección por el VIH en el Caribe. Este análisis toma en cuenta diferentes puntos de vista acerca de cómo Cuba alcanzó ese estatus y busca identificar los elementos clave de su éxito relativo. Contrario a lo expresado por una buena parte de la literatura extranjera, el aislamiento de los pacientes desempeñó un papel menor. Desde la perspectiva de los cubanos, los elementos de mayor peso fueron: la cooperación intersectorial, la vigilancia epidemiológica, la educación, la búsqueda dirigida y el tamizaje de los contactos, la cobertura gratuita de la salud pública y la solidaridad social. Los enfoques desarrollados más recientemente han sido la promoción de salud, la inclusión sexual, el programa llamado "hospital de día", la educación continua de los pacientes, un mayor papel de los pares educadores y la cobertura de 100% de los seropositivos con el tratamiento antirretroviral. [ABSTRACT FROM AUTHOR]

Differences in drug response in patients of various ages including children and the elderly are common, often leading to challenges in optimizing dosages and duration of use. For example, developmental changes in renal function can dramatically alter the plasma clearance of compounds with extensive renal elimination and thus can enhance renal and systemic toxicity of these drugs. Preclinical and clinical research of new therapeutics is initially focused on adults, and provides little relevant information for children especially those who are still going through skeletal and organ development. The organ systems in the pediatric population that can be most susceptible are lungs, brain, kidneys, immune, skeletal, and reproductive systems. Considering that significant differences can exist between adult and juvenile populations that may affect drug safety, major regulatory agencies around the world are encouraging and sometimes requiring companies to generate preclinical juvenile animal data to predict for potential drug toxicity in children. However, data generated from such studies are useful only if obtained using the most appropriate species at the most relevant age considering comparability of specific organ system development in question. Other factors in the design of juvenile safety studies should include the indication, existing toxicological data and likely route of human exposure. This report will discuss these factors with a focus on reviewing species-specific developmental schedules for specific target organs and relevance of preclinical data in the design and conduct of clinical pediatric studies. Specific examples will be used to discuss the relationship of preclinical juvenile toxicity observations to risk assessment in humans. [ABSTRACT FROM AUTHOR]

The Regional Assistance Mission Solomon Islands (RAMSI) was an intervention force requested by the Solomon Islands Government to help stabilise the country after a period of civil strife. It became an experiment in cooperative intervention at a time of uninvited intervention, elsewhere and exercised the imagination of a number of failed state theorists. After more than five years, and with the evaporation of initial rationales that instability in the Solomon Islands might pose a terrorist threat, much uncertainty remains over its future. On the one hand, RAMSI as a security force still enjoys broad support. On the other hand, it has brought a number of new problems. This article explains the origins of RAMSI, including the tensions of 2006-2007 and surveys of Solomon Islander responses to the mission. Using the evidence of informed local voices, it discusses aid trauma , the harmful side-effects of a long term, conspicuously wealthy foreign occupation. The elements of aid trauma are: an inflationary bubble economy, failures in domestic institution building and training, and relative deprivation. The article addresses the question, raised by deep interventionists , as to whether the Solomon Islands has progressed in living standards since independence. As a means of reflecting on the future of RAMSI, I juxtapose Australian state building notions with Solomon Islander views on the role of RAMSI in their relatively new self-governing society. This leads to concluding reflections on the future of RAMSI. [ABSTRACT FROM AUTHOR]

We reviewed the clinical and laboratory oculomotor features in 30 patients with probable multiple system atrophy (MSA), 22 with MSA-P and 8 with MSA-C. Six patients were also examined post mortem, MSA being confirmed in four and excluded in two (Parkinson's disease and progressive supranuclear palsy). Clinical examination showed the following abnormalities; excessive square wave jerks-21 of 30 patients; mild vertical supranuclear gaze palsy-8 of 30; gaze-evoked nystagmus-12 of 30 patients, three of whom had no extraocular evidence of cerebellar dysfunction; positioning downbeat nystagmus-10 of 25; mild or moderate saccadic hypometria-22 of 30; impaired ('broken up') smooth pursuit-28 of 30; reduced VOR suppression-16 of 24. Electro-oculography and caloric testing did not add significant extra information. In patients presenting with an akinetic-rigid syndrome it can be difficult to differentiate idiopathic Parkinson's disease from MSA-P and other causes of atypical parkinsonism. Our findings suggest that the presence of excessive square wave jerks, mild - moderate hypometria of saccades, impaired VOR suppression, spontaneous nystagmus or positioning downbeat nystagmus may be oculomotor 'red flags' or clues to the presence of MSA. Further, the presence of clinically slow saccades, or moderate-to-severe gaze restriction, suggests a diagnosis other than MSA. © 2008 Movement Disorder Society [ABSTRACT FROM AUTHOR]

The article presents a summary of current knowledge on concussion and mild head injury and the treatments to be used. The definition, grading, epidemiology and pathogenesis of mild head injury are discussed. Early post-concussive symptoms and early intervention effectiveness from randomized controlled trials are also described.

The OECD's Guidelines on Poverty and Health are compromised by neoliberal assumptions and corrupted by several major conflicts of interest. These conflicts of interest are embodied in the DAC guidelines, whereby specific OECD commercial interests influence the public policies of developing countries. Commercial agendas are being incorporated into developing country health policy through development assistance doctrine. Yet better critical health outcomes generally occur in the well-coordinated, public health systems, rather than those with high levels of private supplementation. This paper examines the OECD Guidelines' construction of public health policy in poor countries, drawing attention to the ideological agenda and linked conflicts of interest. [ABSTRACT FROM AUTHOR]

Abstract: Understanding the frequency with which new resistance alleles arise and their subsequent patterns of spread is critical to our attempts to manage drug resistance in parasite populations. We review recent molecular evolutionary studies utilizing marker loci situated close to resistance loci on the Plasmodium falciparum genome that have given surprising insights into the origins and spread of drug resistance loci. We discuss possible reasons for the patterns observed, and highlight the implications of these results for resistance management. In particular, we show that many resistance mutations have rather few independent origins. De novo mutation appears to be less important than migration for introducing resistance alleles into parasite populations. Attempts to manage drug resistance will be of limited effectiveness unless this is taken into account. [Copyright &y& Elsevier]

Focuses on the national recording bans of the American Federation of Musicians (AMF) in the U.S. Argument of musicians on the inability of the government to control recording technologies; Concerns of the AMF or union; Resistance to new technologies through recording strikes.

Aims: To assess resistance to chloroquine (CQ) and sulphadoxine/pyrimethamine (SP) in a Sudanese parasite population.Methods: Recurrent security problems in Akuem, Sudan, prevented us from conducting a classical in vivo treatment efficacy study. Instead we genotyped key mutations in the chloroquine resistance transporter (pfcrt), the multidrug resistance gene (pfmdr1), dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps). We genotyped the K76T mutation in pfcrt and the N86Y mutation in (pfmdr) by restriction digestion of fluorescent end-labelled polymerase chain reaction (PCR) products, while we genotyped codons 16, 51, 59, 108 and 164 in dhfr and codons 436, 437, 540, 581 and 613 in dhps by primer extension in 100 blood samples.Results: Sixty-three percent of parasites carried the 76T mutation at pfcrt critical for CQ resistance, while 31% carried the 86Y mutation at pfmdr that is associated with, although not essential, for CQ resistance. We found five dhfr alleles: 60% of infections contained wild-type dhfr alleles, 3% had one mutation, 34% had two mutations, while 3% had three mutations. We found three dhps alleles: 47% were wild type, 44% had one mutation, while 9% had two mutations.Conclusions: We expect high levels of treatment failure (RI-RIII) with CQ (20-40%) and predict efficient treatment with SP. However, dhfr alleles with three mutations (51I, 59R, 108N) are present as are dhps alleles with two mutations (437G, 540E). Successful treatment with SP is therefore likely to be short-lived. [ABSTRACT FROM AUTHOR]

Background. Developmental stuttering affects 1% of the population but its cause remains unclear. Recent PET studies of metabolism in the central nervous system suggest that it may be related to dysfunction in the basal ganglia or its connections with regions of the cortex associated with speech and motor control.Objective. To determine the presence and characteristics of involuntary movements (IMs) in people who stutter and to investigate the hypothesis that these movements may be of a very similar nature to the IMs seen in patients with movement disorders due to basal ganglia dysfunction.Methods. Sixteen adults with developmental stuttering and 16 controls matched for sex and age were audio–videotaped while freely speaking 300 words in conversation and reading aloud 300 words. The audio data was inspected for dysfluencies and the video data was scrutinised for the presence and characteristics of IMs.Results. Subjects who stuttered produced more IMs than controls during free speech (354 vs 187, p<0.05) and reading (297 vs 47, p<0.001). Most of the IMs in both groups were tics, with a greater number of both simple and complex motor tics (CMTs) in subjects who stuttered. CMTs were more frequent than simple motor tics in those who stuttered, but not in controls. The combination of repetitive eye blink followed by prolonged eye closure was found exclusively in the stuttering group, as were simple tics consisting of eyebrow raise or jaw movement. Dystonia in the form of blepharospasm was identified in a small number of subjects who stuttered. Choreic movements were not associated with stuttering.Conclusions. Developmental stuttering is associated with the presence of IMs that are predominantly simple and CMTs. This association suggests that tics and stuttering may share a common pathophysiology and supports the view that, in common with tics, stuttering may reflect dysfunction in the basal ganglia or its immediate connections. [Copyright &y& Elsevier]

Investigates the presence and characteristics of involuntary movements (IM) accompanying stuttering. Level on the proportion of classic dysfluencies in stuttering subjects; Observation of IM on subjects during fluent speech; Indication for the variation of etiologies in classic and normal dysfluency.

The article discusses relationship between the performance of live music and film. It says that although recent scholarship has utilized numerous approaches and disciplines to understand various issues involved in film exhibition, the need to understand the performative aspects of exhibition has been sorely underestimated. Investigation into issues of film sound and music have resulted in a fine and elaborate understanding of the nature of narrative film music scoring and arranging, with specific attention placed on the use of soundtrack recordings in classical Hollywood cinema. Music in silent cinema had accompanied other forms of spectacle before and was a convention that successfully persisted, it covered the distracting noise of the movie projector, it had semiotic functions in the narrative and it provide a rhythmic beat to complement or impel the rhythms of editing and movement on the screen.

Deficits in memory performance have been linked to a wide range of neurological and neuropsychiatric conditions. While many studies have assessed the memory impacts of individual conditions, this study considers a broader perspective by evaluating how memory recall is differentially associated with nine common neuropsychiatric conditions using data drawn from 55 international studies, aggregating 15,883 unique participants aged 15–90. The effects of dementia, mild cognitive impairment, Parkinson's disease, traumatic brain injury, stroke, depression, attention-deficit/hyperactivity disorder (ADHD), schizophrenia, and bipolar disorder on immediate, short-, and long-delay verbal learning and memory (VLM) scores were estimated relative to matched healthy individuals. Random forest models identified age, years of education, and site as important VLM covariates. A Bayesian harmonization approach was used to isolate and remove site effects. Regression estimated the adjusted association of each clinical group with VLM scores. Memory deficits were strongly associated with dementia and schizophrenia (p < 0.001), while neither depression nor ADHD showed consistent associations with VLM scores (p > 0.05). Differences associated with clinical conditions were larger for longer delayed recall duration items. By comparing VLM across clinical conditions, this study provides a foundation for enhanced diagnostic precision and offers new insights into disease management of comorbid disorders. [ABSTRACT FROM AUTHOR]

Background: Artemisinin resistance in Plasmodium falciparum threatens global malaria elimination efforts. To contain and then eliminate artemisinin resistance in Eastern Myanmar a network of community-based malaria posts was instituted and targeted mass drug administration (MDA) with dihydroartemisinin-piperaquine (three rounds at monthly intervals) was conducted. The prevalence of artemisinin resistance during the elimination campaign (2013–2019) was characterized. Methods: Throughout the six-year campaign Plasmodium falciparum positive blood samples from symptomatic patients and from cross-sectional surveys were genotyped for mutations in kelch-13—a molecular marker of artemisinin resistance. Result: The program resulted in near elimination of falciparum malaria. Of 5162 P. falciparum positive blood samples genotyped, 3281 (63.6%) had K13 mutations. The prevalence of K13 mutations was 73.9% in 2013 and 64.4% in 2019. Overall, there was a small but significant decline in the proportion of K13 mutants (p < 0.001). In the MDA villages there was no significant change in the K13 proportions before and after MDA. The distribution of different K13 mutations changed substantially; F446I and P441L mutations increased in both MDA and non-MDA villages, while most other K13 mutations decreased. The proportion of C580Y mutations fell from 9.2% (43/467) before MDA to 2.3% (19/813) after MDA (p < 0.001). Similar changes occurred in the 487 villages where MDA was not conducted. Conclusion: The malaria elimination program in Kayin state, eastern Myanmar, led to a substantial reduction in falciparum malaria. Despite the intense use of artemisinin-based combination therapies, both in treatment and MDA, this did not select for artemisinin resistance. [ABSTRACT FROM AUTHOR]

Oculomotor assessment is an essential element of the neurological clinical examination and is particularly important when evaluating patients with movements disorders. Most of the brain is involved in oculomotor control, and thus many neurological conditions present with oculomotor abnormalities. Each of the different classes of eye movements and their features can provide important information that can facilitate differential diagnosis. This educational review presents a clinical approach to eye movement abnormalities that are commonly seen in parkinsonism, ataxia, dystonia, myoclonus, tremor, and chorea. In parkinsonism, subtle signs such as prominent square wave jerks, impaired vertical optokinetic nystagmus, and/or the "round the houses" sign suggest early progressive supranuclear gaze palsy before vertical gaze is restricted. In ataxia, nystagmus is common, but other findings such as oculomotor apraxia, supranuclear gaze palsy, impaired fixation, or saccadic pursuit can contribute to diagnoses such as ataxia with oculomotor apraxia, Niemann‐Pick type C, or ataxia telangiectasia. Opsoclonus myoclonus and oculopalatal myoclonus present with characteristic phenomenology and are usually easy to identify. The oculomotor exam is usually unremarkable in isolated dystonia, but oculogyric crisis is a medical emergency and should be recognized and treated in a timely manner. Gaze impersistence in a patient with chorea suggests Huntington's disease, but in a patient with dystonia or tremor, Wilson's disease is more likely. Finally, functional eye movements can reinforce the clinical impression of a functional movement disorder. [ABSTRACT FROM AUTHOR]

In western Cambodia, malaria parasites clear slowly from the blood after treatment with artemisinin derivatives, but it is unclear whether this results from parasite, host, or other factors specific to this population. We measured heritability of clearance rate by evaluating patients infected with identical or nonidentical parasite genotypes, using methods analogous to human twin studies. A substantial proportion (56%-58%) of the variation in clearance rate is explained by parasite genetics. This has 2 important implications: (1) selection with artemisinin derivatives will tend to drive resistance spread and (2) because heritability is high, the genes underlying parasite clearance rate may be identified by genome-wide association. [ABSTRACT FROM AUTHOR]