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Treatment resistant schizophrenia (TRS) is one of the most disabling of psychiatric disorders, affecting about 1/3 of patients. First-line treatments include both atypical and typical antipsychotics. The original atypical, clozapine, is a final option, and although it has been shown to be the only effective treatment for TRS, many patients do not respond well to clozapine. Clozapine use is related to adverse events, most notably agranulocytosis, a potentially fatal blood disorder which affects about 1% of those prescribed clozapine and requires regular blood monitoring. This as a barrier to prescription and there is a long delay in access for TRS patients, of five or more years, from first antipsychotic prescription. Better tools to predict treatment resistance and to identify risk of adverse events would allow faster and safer access to clozapine for patients who are likely to benefit from it. The CRESTAR project (www.crestar-project.eu) is a European Framework 7 collaborative project that aims to develop tools to predict i) treatment response, particularly patients who are less likely to respond to usual antipsychotics, indicating treatment with clozapine as early as possible, ii) patients who are at high or low risk of adverse events and side effects, iii) extreme TRS patients so that they can be stratified in clinical trials for novel treatments. CRESTAR has addressed these questions by examining genome-wide association data, genome sequence, epigenetic biomarkers and epidemiological data in European patient cohorts characterized for treatment response, and adverse drug reaction using data from clozapine therapeutic drug monitoring and linked National population medical and pharmacy databases, to identify predictive factors. In parallel CRESTAR will perform health economic research on potential benefits, and ethics and patient-centred research with stakeholders.
To date, Ireland has been a leading light in the provision of youth mental health services. However, cognisant of the efforts of governmental and non-governmental agencies working in youth mental health, there is much to be done. Barriers into care as well as discontinuity of care across the spectrum of services remain key challenges. This editorial provides guidance for the next stage of development in youth mental care and support that will require significant national engagement and resource investment.
An unlinked anonymous study was conducted to estimate the prevalence of hepatitis C virus (HCV) infection in emergency department (ED) attendees at a London Hospital. Nine hundred and ninety-seven samples collected over a 12-day period were tested for HCV antibody (Ab) and reactive samples were further tested for HCV RNA. The HCV seroprevalence was 2·6% (26/997) with 1·2% (12/997) HCV RNA positive. A peak HCV RNA-positive prevalence of 4·8% (3/63) was found in males aged 35–44 years, this was compared to 0% (0/136) in males aged <35 years (P = 0·0614) and 1·4% (4/278) in males aged ⩾45 years (P = 0·2415). Assuming the cost for HCV Ab is £6 and HCV RNA is £40 per test, screening ED attendees aged 25–54 years would cost £360 per viraemic infection and identify 82% of those who were HCV RNA positive, yielding the most favourable cost/benefit ratio. HCV screening of ED attendees aged 25–54 years in this population could be an effective way of identifying patients and limit onward transmission.
The ability to design a diagnostics platform that can achieve cellular level as well as molecular level classification of targeted biomarkers may be critical toward understanding the fundamental basis of disease initiation and proliferation in breast cancer. In this context, we have looked at breast cancer diagnostics and present the design of a biomedical microdevice for evaluating and classifying cellular samples based on their risk towards metastasis. Primary breast cancer tumors have been shown to contain heterogeneous populations of neoplastic cells. Recent studies have demonstrated that subpopulations of these cells can cooperate in the initiation of collective invasion and metastasis. The role of the sensor we present is to identify the type of cells as non-invasive/”follower” cells that do not result in metastasis or invasive “leader” cells that are thought to be responsible for metastasis, from breast cancer cell lysate samples, thus enabling more selective classification of samples, with the eventual goal of early diagnosis. The device is an electrical immunoassay that incorporates the PDGF- receptor to screen the cell lysate samples for the PGDF binding protein that is preferentially expressed in the invasive, “leader” cells. The sensor comprises of alumina nanochannel arrays integrated on to a microelectronic platform operating on the principle of electrochemical impedance spectroscopy to quantify the PGDF protein from the cell lysates.
To report a large outbreak of Clostridium difficile infection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak.
Outbreak investigation in 3 acute care hospitals of the Northern Health and Social Care Trust in Northern Ireland.
Implementation of a series of CDI control measures that targeted high-risk antibiotic agents (ie, restriction of fluoroquinolones), infection control practices, and environmental hygiene.
A total of 318 cases of CDI were identified during the outbreak, which was the result of the interaction between C. difficile ribotype 027 being introduced into the affected hospitals for the first time and other predisposing risk factors (ranging from host factors to suboptimal compliance with antibiotic guidelines and infection control policies). The 30-day all-cause mortality rate was 24.5%; however, CDI was the attributable cause of death for only 2.5% of the infected patients. Time series analysis showed that restricting the use of fluoroquinolones was associated with a significant reduction in the incidence of CDI (coefficient, —0.054; lag time, 4 months; P = .003).
These findings provide additional evidence to support the value of antimicrobial stewardship as an essential element of multifaceted interventions to control CDI outbreaks. The present CDI outbreak was ended following the implementation of an action plan improving communication, antibiotic stewardship, infection control practices, environmental hygiene, and surveillance.
Differences in reported hand hygiene compliance rates were assessed on the basis of the unit affiliation of observers. In 2 hospitals, unit-based observers more often reported higher compliance rates than did non-unit-based observers (79% vs 58.6%; difference, 20.4%; P<.001). Nonstandardized data collection methods contribute to the variability in hand hygiene compliance rates.
Series of action phases characterize natural object manipulation tasks where each phase is responsible for satisfying a task subgoal. Subgoal attainment typically corresponds to distinct mechanical contact events, either involving the making or breaking of contact between the digits and an object or between a held object and another object. Subgoals are realized by the brain selecting and sequentially implementing suitable action-phase controllers that use sensory predictions and afferents signals in specific ways to tailor the motor output in anticipation of requirements imposed by objects' physical properties. This chapter discusses the use of tactile and visual sensory information in this context. It highlights the importance of sensory predictions, especially related to the discrete and distinct sensory events associated with contact events linked to subgoal completion, and considers how sensory signals influence and interact with such predictions in the control of manipulation tasks.
Sensory systems supporting object manipulation
In addition to multiple motor systems (arm, hand, posture), most natural object manipulation tasks engage multiple sensory systems. Vision provides critical information for control of task kinematics. In reaching, we use vision to locate objects in the environment and to identify contact sites for the digits that will be stable and advantageous for various actions we want to perform with the grasped object (Goodale et al., 1994; Santello & Soechting, 1998; Cohen & Rosenbaum, 2004; Cuijpers et al., 2004; Lukos et al., 2007).
Skilled object manipulation requires the ability to estimate, in advance, the motor commands needed to achieve desired sensory outcomes and the ability to predict the sensory consequences of the motor commands. Because the mapping between motor commands and sensory outcomes depends on the physical properties of grasped objects, the motor system may store and access internal models of objects in order to estimate motor commands and predict sensory consequences. In this chapter, we outline evidence for internal models and discuss their role in object manipulation tasks. We also consider the relationship between internal models of objects employed by the sensorimotor system and representations of the same objects used by the perceptual system to make judgements about objects.
Although we have designed computers that can beat grand masters at chess, we have yet to design robots that can manipulate chess pieces with anything like the dexterity of a 5-year-old child. What makes humans so good at object manipulation in comparison to robots? There is no question that the anatomy of the human hand is well adapted for manipulation. On the sensory side, the hand is richly endowed with tactile sensors that provide exquisitely precise information about mechanical interactions between the skin and objects. On the motor side, the numerous kinematic degrees of freedom of the hand enable it to grasp objects of all shapes and sizes.
1. A new semi-dominant gene called shaven (Sha) causes hairlessness in the mouse and it is closely linked to naked. Homozygous shaven mice never grow a first coat and adults grow a few short hairs only. Shaven heterozygotes grow a full coat which is greasy.
2. The percentage recombination between shaven and naked was found to be 0·8%. Three-point tests with naked and caracul showed that the order of the three loci is either N–Sha–Ca or N–Ca–Sha.
3. The failure of homozygous shaven mice to grow a coat is due to abnormal keratinization of the hairs in the follicles. The follicles were found to be deficient in sulphydryl groups.
4. The greasiness of the Sha+ coat is due to the presence of a sudanophilic fluid in the hair medullae.
5. The close linkage between the two genes with similar phenotypic effects is discussed.