Miracle-dz/UniFAR-FTUs huggingface dataset:
Partnering in primary care in New Zealand: clients’ and nurses’ experience of the Flinders Program™ in the management of long-term conditions

roy de, mahony f, horsburgh m & bycroft j (2011) Journal of Nursing and Healthcare of Chronic Illness3, 140–149 Partnering in primary care in New Zealand: clients’ and nurses’ experience of the Flinders Program™ in the management of long-term conditions Aim and Objectives. To explore clients’ and nurses’ experience of the Flinders Program™ of self-management within a study assessing the feasibility for a trial gauging the effectiveness of the Flinders Program™ in New Zealand (NZ). Background. The Flinders Program™ has been adopted in NZ as a useful and appropriate approach for improving long-term condition management; approximately 500 health professionals have been trained in its use. Evidence for the effectiveness of self-management is inconclusive and support for introduction of new and complex interventions in primary care inconsistent. Design. The feasibility study used mixed methods with simultaneous qualitative and quantitative components, including a web-based survey. The qualitative component, reported here, used interpretive description. Method. In 2009, two focus groups were conducted with nurses participating in the intervention group of the feasibility study together with interviews of 11 clients with long-term conditions who had completed Flinders assessments and four nurses who partnered with these clients. Free-text responses from survey participants (n = 355) who had completed ‘Flinders’ training in NZ since 2005 were included in the interpretative analysis. Findings. Three themes describe the experience of clients and nurses: ‘enablers and benefits’ with sub-themes of process, relationships and time; ‘challenges’ with sub-themes of motivation, resistance to change, primary care structure and time. ‘A catalyst for change’ is the third theme. Conclusion. While implementation of the Flinders Program™ in NZ is limited, there are benefits of the approach for clients and nurses in terms of greater understanding of self-management, collaborative care and effective strategies to support client behaviour change. There are, however, challenges in facilitating such programs in primary care. Relevance to clinical practice. Understanding the experience of the Flinders Program™ in primary care illustrates the value of supported self-management for clients with long-term conditions, while highlighting the challenges of implementing new and complex interventions.
Serum protein profiling by solid phase extraction and mass spectrometry: A future diagnostics tool?

Serum protein profiling by MS is a promising method for early detection of disease. Important characteristics for serum protein profiling are preanalytical factors, analytical reproducibility and high throughput. Problems related to preanalytical factors can be overcome by using standardized and rigorous sample collection and sample handling protocols. The sensitivity of the MS analysis relies on the quality of the sample; consequently, the blood sample preparation step is crucial to obtain pure and concentrated samples and enrichment of the proteins and peptides of interest. This review focuses on the serum sample preparation step prior to protein profiling by MALDI MS analysis, with particular focus on various SPE methods. The application of SPE techniques with different chromatographic properties such as RP, ion exchange, or affinity binding to isolate specific subsets of molecules (subproteomes) is advantageous for increasing resolution and sensitivity in the subsequent MS analysis. In addition, several of the SPE sample preparation methods are simple and scalable and have proven easy to automate for higher reproducibility and throughput, which is important in a clinical proteomics setting.
Retinal inner nuclear layer volume reflects response to immunotherapy in multiple sclerosis.

Assessment of inflammatory disease activity during multiple sclerosis is crucial for selecting appropriate disease- modifying therapies. Previous studies suggested that the retinal inner nuclear layer reflects inflammatory disease severity within the central nervous system. In our study, correlations of longitudinal retinal layer changes as measured by retinal optical coherence tomography with ongoing disease activity were evaluated in 108 multiple sclerosis patients without therapy, on first- line therapy, or on second- line therapy. Healthy subjects served as controls. Inner nuclear layer volume at baseline correlated positively with paraclinical disease activity during the subsequent 12 months. Longitudinal thinning of the inner nuclear layer and thickening of total macular volume were associated with reduced inflammatory disease activity. Reduction in inner nuclear layer volume after 1 year indicated efficient control of inflammatory disease activity including ` no evidence of disease activity'. In conclusion, the retinal inner nuclear layer could serve as biomarker to monitor sustained control of autoimmune central nervous system inflammation by therapeutic interventions.
Miscellaneous Disorders of the Equine Nervous System: Horner's Syndrome and Polyneuritis Equi

Horner’s syndrome is the collection of clinical signs caused by sympathetic denervation of structures of the head. Lesions can be in the brainstem, spinal cord, thoracic outflow, sympathetic trunk, cranial cervical ganglion, or postganglionic axons in the head. The most common clinical signs in horses are sweating in the acute disease and prominent ptosis with decreased angle of the eyelashes. Associated clinical signs in associated structures allow the site of the lesion to be determined and a therapeutic and prognostic plan to be made. Polyneuritis equi is an uncommon neurologic disease of mature horses and ponies, principally characterized by clinical signs relating to chronic granulomatous inflammation of the cauda equina. Involvement of other nerves, particularly cranial nerves, is recognized, however, and the term polyneuritis equi is preferable and has superceded the older descriptive name of neuritis of the cauda equina.
Improving sensitivity in proteome studies by analysis of false discovery rates for multiple search engines

LC‐MS experiments can generate large quantities of data, for which a variety of database search engines are available to make peptide and protein identifications. Decoy databases are becoming widely used to place statistical confidence in result sets, allowing the false discovery rate (FDR) to be estimated. Different search engines produce different identification sets so employing more than one search engine could result in an increased number of peptides (and proteins) being identified, if an appropriate mechanism for combining data can be defined. We have developed a search engine independent score, based on FDR, which allows peptide identifications from different search engines to be combined, called the FDR Score. The results demonstrate that the observed FDR is significantly different when analysing the set of identifications made by all three search engines, by each pair of search engines or by a single search engine. Our algorithm assigns identifications to groups according to the set of search engines that have made the identification, and re‐assigns the score (combined FDR Score). The combined FDR Score can differentiate between correct and incorrect peptide identifications with high accuracy, allowing on average 35% more peptide identifications to be made at a fixed FDR than using a single search engine.
MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden

Perivascular spaces that are visible on magnetic resonance imaging (MRI) are a neuroimaging marker of cerebral small vessel disease. Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, while those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis. As cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment. We also hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with brain amyloid burden, as detected by amyloid positron emission tomography using 11C-Pittsburgh B compound (PiB-PET). Two hundred and twenty-six patients (Alzheimer's disease n = 110; subcortical vascular cognitive impairment n = 116) with standardized MRI and PiB-PET imaging were included. MRI-visible perivascular spaces were rated using a validated 4-point visual rating scale, and then categorized by severity ('none/mild', 'moderate' or 'frequent/severe'). Univariable and multivariable regression analyses were performed. Those with Alzheimer's disease-related cognitive impairment were younger, more likely to have a positive PiB-PET scan and carry at least one apolipoprotein E ɛ4 allele; those with subcortical vascular cognitive impairment were more likely to have hypertension, diabetes mellitus, hyperlipidaemia, prior stroke, lacunes, deep microbleeds, and carry the apolipoprotein E ɛ3 allele. In adjusted analyses, the severity of MRI-visible perivascular spaces in the centrum semi-ovale was independently associated with clinically diagnosed Alzheimer's disease (frequent/severe grade odds ratio 6.26, 95% confidence interval 1.66-23.58; P = 0.017, compared with none/mild grade), whereas the severity of MRI-visible perivascular spaces in the basal ganglia was associated with clinically diagnosed subcortical vascular cognitive impairment and negatively predicted Alzheimer's disease (frequent/severe grade odds ratio 0.03, 95% confidence interval 0.00-0.44; P = 0.009, compared with none/mild grade). MRI-visible perivascular space severity in either location did not predict PiB-PET. These findings provide further evidence that the anatomical distribution of MRI-visible perivascular spaces may reflect the underlying cerebral small vessel disease. Using MRI-visible perivascular space location and severity together with other imaging markers may improve the diagnostic value of neuroimaging in memory clinic populations, in particular in differentiating between clinically diagnosed Alzheimer's and subcortical vascular cognitive impairment.
Decreased integration and information capacity in stroke measured by whole brain models of resting state activity

While several studies have shown that focal lesions affect the communication between structurally normal regions of the brain, and that these changes may correlate with behavioural deficits, their impact on brain's information processing capacity is currently unknown. Here we test the hypothesis that focal lesions decrease the brain's information processing capacity, of which changes in functional connectivity may be a measurable correlate. To measure processing capacity, we turned to whole brain computational modelling to estimate the integration and segregation of information in brain networks. First, we measured functional connectivity between different brain areas with resting state functional magnetic resonance imaging in healthy subjects (n = 26), and subjects who had suffered a cortical stroke (n = 36). We then used a whole-brain network model that coupled average excitatory activities of local regions via anatomical connectivity. Model parameters were optimized in each healthy or stroke participant to maximize correlation between model and empirical functional connectivity, so that the model's effective connectivity was a veridical representation of healthy or lesioned brain networks. Subsequently, we calculated two model-based measures: 'integration', a graph theoretical measure obtained from functional connectivity, which measures the connectedness of brain networks, and 'information capacity', an information theoretical measure that cannot be obtained empirically, representative of the segregative ability of brain networks to encode distinct stimuli. We found that both measures were decreased in stroke patients, as compared to healthy controls, particularly at the level of resting-state networks. Furthermore, we found that these measures, especially information capacity, correlate with measures of behavioural impairment and the segregation of resting-state networks empirically measured. This study shows that focal lesions affect the brain's ability to represent stimuli and task states, and that information capacity measured through whole brain models is a theory-driven measure of processing capacity that could be used as a biomarker of injury for outcome prediction or target for rehabilitation intervention.
Balance, Falls Risk, and Related Disability in Untreated Vestibular Schwannoma Patients

Abstract Background Many vestibular schwannoma (VS) patients complain of balance dysfunction; however, validated standardized assessments are lacking. The relative contribution of imbalance and factors like anxiety to disability is unknown. Because imbalance significantly affects quality of life in this group and vestibular rehabilitation may improve outcomes, determining the severity of balance dysfunction is important to understand long-term rehabilitation needs. Aim To assess functional balance (Vertigo Symptom Scale-Vertigo [VSS-VER] and Functional Gait Assessment [FGA]) and the relative contribution of symptom severity (VSS-VER), ambulant posture (FGA), and anxiety symptoms (Vertigo Symptom Scale-Anxiety [VSS-SA]) to disability in untreated patients. Methods Patients not exposed to surgery completed the VSS, Vertigo Handicap Questionnaire (VHQ), and FGA. VSS scores were compared with migrainous vertigo (MV) patients, a mixed neuro-otological group, and healthy controls. Results A correlation was found between decreased FGA and increasing age (r = − 0.35; p < 0.01), female sex (r = 0.42; p = 0.001), increasing handicap (r = − 0.55; p < 0.001), and symptom severity (r = − 0.52; p < 0.001). In 12 of 21 patients (57%) > 60 years of age the FGA score was ≤ 22 suggesting increased falls risk. VSS-VER scores were higher than in healthy controls (p < 0.001) but lower than MV (p < 0.001) and mixed neuro-otology controls (p < 0.001). VSS-SA scores in VS patients with balance symptoms were higher than normal controls (p < 0.05) and correlated with handicap (r = 0.59; p < 0.001) and symptom severity (r = 0.74; p < 0.001). After controlling for age and sex, the VSS-VER, VSS-SA, and FGA explained 47% of the variation in VHQ scores. Conclusion Older VS patients are at significant risk of falls. Balance symptoms are more severe than in healthy controls but less than other neuro-otological patients. Balance symptom severity, anxiety symptoms, and ambulant posture were significant contributors to disability and should be the focus of vestibular rehabilitation strategies.
Proteomics of mouse liver microsomes: Performance of different protein separation workflows for LC‐MS/MS

The mouse liver microsome proteome was investigated using ion trap MS combined with three separation workflows including SDS‐PAGE followed by reverse‐phase LC of in‐gel protein digestions (519 proteins identified); 2‐D LC of protein digestion (1410 proteins); whole protein separation on mRP heat‐stable column followed by 2‐D LC of protein digestions from each fraction (3‐D LC; 3703 proteins). The higher number of proteins identified in the workflow corresponded to the lesser percentage of run‐to‐run reproducibility. Gel‐based method yielded a number of predicted membrane proteins similar to LC‐based workflows.
What is Important to Young Children Who Have Cancer While in Hospital

This paper reports on a participatory research project exploring children's experiences and views of cancer care services. It focusses on findings from interviews conducted with 10 children aged four and five years old. Play and puppets were used to help children express their views. The themes elicited reveal important aspects of hospital care for young children, such as having 'lots of toys' available and that 'mummy and daddy are near'. The use of play and puppets as a data-collection method is discussed, along with the implications of findings for the care and support of young children who have cancer.
The effects of nocturnal dipping on cardiovascular outcomes and proteinuria in essential hypertensive patients

Individuals who do not have a 10% to 20% reduction in blood pressure (BP) during the night are known as ‘nondippers’. Non-dipping patterns in hypertensive patients have been shown to be associated with an excess of target organ damage and other adverse outcomes. The present study was designed to investigate the relationship between nocturnal BP pattern, defined on the basis of the ambulatory blood pressure monitoring (ABPM) recording, and cardiac and renal target organ damage in a population of at least one year treated essential hypertensive subjects. The present analysis involved 123 patients with treated essential hypertension attending the outpatient clinic of our centre. Each patient was subjected to the following procedures: blood sampling for routine blood chemistry, spot urine for proteinuria, 24-hour periods of ABPM, and echocardiography. In the ABPM period, a dipping pattern was observed in 65 of the 123 patients, and a non-dipping pattern in 58 patients. Body mass index was higher in the non-dippers (26 ± 4 versus 28 ± 4, p<0.05). The proteinuria in spot urine was significantly higher in the non-dippers (10 ± 6 versus 24 ± 48, p<0.03). Left ventricular mass, interventricular septum thickness, posterior wall thickness and left ventricular systolic diameter were significantly higher in the non-dippers compared to the dippers. Left ventricular diastolic function was similar in non-dipper cases, except E-wave deceleration time. In treated essential hypertensives the blunted or absent nocturnal fall in blood pressure can be a strong predictor of cardiac and renal events. Hypertensive patients should be evaluated by ambulatory blood pressure monitoring. To prevent patients at risk for morbidity and mortality casualities as a result of hypertension, patients should be evaluated by ambulatory blood pressure monitoring. This method can be utilized for exacting future follow-ups with the patient.
MALDI‐TOF MS‐based drug susceptibility testing of pathogens: The example of Candida albicans and fluconazole

MALDI‐TOF MS can be used for the identification of microorganism species. We have extended its application to a novel assay of Candida albicans susceptibility to fluconazole, based on monitoring modifications of the proteome of yeast cells grown in the presence of varying drug concentrations. The method was accurate, and reliable, and showed full agreement with the Clinical Laboratory Standards Institute's reference method. This proof‐of‐concept demonstration highlights the potential for this approach to test other pathogens.
Using an engineered glutamate-gated chloride channel to silence sensory neurons and treat neuropathic pain at the source

See Basbaum (doi:10.1093/brain/awx227) for a scientific commentary on this article. Following nerve injury, sensory neurons become hyperexcitable and this is a key driver of neuropathic pain. Weir et al. develop a gene therapy approach that silences sensory neurons and reversibly normalizes pain thresholds in animal models of neuropathic pain. This new approach has significant translational potential.
Dementia in United States nursing homes: Descriptive epidemiology and implications for long-term residential care

Using data from the 1985 National Nursing Home Survey, the health and functioning of demented and non-demented nursing home residents are compared, and alternate forms of long-term residential care are identified. The 1985 National Nursing Home Survey is a cross-sectional investigation of residents in 1079 nursing and related care homes in the United States. Subjects for comparative analyses include 4622 residents age 65 and older from these facilities. Fifty-one percent had a diagnosis of dementia. Compared with non-demented residents, those with dementia had more impairments in physical and instrumental tasks of daily living, behavioral problems, and psychiatric symptoms, and fewer physical health comorbidities. Although statistically significant, many of the differences were small. Analyses indicate that there is considerable overlap in the health and functional status of nursing home residents with and without dementia. Both groups are heterogeneous in health and functioning and both have members with.
Mutations of AKT3 are associated with a wide spectrum of developmental disorders including extreme megalencephaly

Mutations of genes within the phosphatidylinositol-3-kinase (PI3K)-AKT-MTOR pathway are well known causes of brain overgrowth (megalencephaly) as well as segmental cortical dysplasia (such as hemimegalencephaly, focal cortical dysplasia and polymicrogyria). Mutations of the AKT3 gene have been reported in a few individuals with brain malformations, to date. Therefore, our understanding regarding the clinical and molecular spectrum associated with mutations of this critical gene is limited, with no clear genotype-phenotype correlations. We sought to further delineate this spectrum, study levels of mosaicism and identify genotype-phenotype correlations of AKT3-related disorders. We performed targeted sequencing of AKT3 on individuals with these phenotypes by molecular inversion probes and/or Sanger sequencing to determine the type and level of mosaicism of mutations. We analysed all clinical and brain imaging data of mutation-positive individuals including neuropathological analysis in one instance. We performed ex vivo kinase assays on AKT3 engineered with the patient mutations and examined the phospholipid binding profile of pleckstrin homology domain localizing mutations. We identified 14 new individuals with AKT3 mutations with several phenotypes dependent on the type of mutation and level of mosaicism. Our comprehensive clinical characterization, and review of all previously published patients, broadly segregates individuals with AKT3 mutations into two groups: patients with highly asymmetric cortical dysplasia caused by the common p.E17K mutation, and patients with constitutional AKT3 mutations exhibiting more variable phenotypes including bilateral cortical malformations, polymicrogyria, periventricular nodular heterotopia and diffuse megalencephaly without cortical dysplasia. All mutations increased kinase activity, and pleckstrin homology domain mutants exhibited enhanced phospholipid binding. Overall, our study shows that activating mutations of the critical AKT3 gene are associated with a wide spectrum of brain involvement ranging from focal or segmental brain malformations (such as hemimegalencephaly and polymicrogyria) predominantly due to mosaic AKT3 mutations, to diffuse bilateral cortical malformations, megalencephaly and heterotopia due to constitutional AKT3 mutations. We also provide the first detailed neuropathological examination of a child with extreme megalencephaly due to a constitutional AKT3 mutation. This child has one of the largest documented paediatric brain sizes, to our knowledge. Finally, our data show that constitutional AKT3 mutations are associated with megalencephaly, with or without autism, similar to PTEN-related disorders. Recognition of this broad clinical and molecular spectrum of AKT3 mutations is important for providing early diagnosis and appropriate management of affected individuals, and will facilitate targeted design of future human clinical trials using PI3K-AKT pathway inhibitors.