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1.
AJNR Am J Neuroradiol ; 43(2): 238-244, 2022 02.
Article in English | MEDLINE | ID: mdl-35121585

ABSTRACT

BACKGROUND AND PURPOSE: Perivascular spaces surround the blood vessels of the brain and are involved in neuroimmune functions and clearance of metabolites via the glymphatic system of the brain. Enlarged perivascular spaces could be a marker of dysfunction in these processes and, therefore, are highly relevant to monitoring disease activity in MS. This study aimed to compare the number of enlarged perivascular spaces in people with relapsing MS with MR imaging markers of inflammation and brain atrophy. MATERIALS AND METHODS: Fifty-nine patients (18 with clinically isolated syndrome, 22 with early and 19 with late relapsing-remitting MS) were scanned longitudinally (mean follow-up duration = 19.6 [SD, 0.5] months) using T2-weighted, T1-weighted, and FLAIR MR imaging. Two expert raters identified and counted enlarged perivascular spaces on T2-weighted MR images from 3 ROIs (the centrum semiovale, basal ganglia, and midbrain). Baseline and change with time in the number of enlarged perivascular spaces were correlated with demographics and lesion and brain volumes. RESULTS: Late relapsing-remitting MS had a greater average number of enlarged perivascular spaces at baseline at the level of the basal ganglia (72.3) compared with early relapsing-remitting MS (60.5) and clinically isolated syndrome (54.7) (F = 3.4, P = .042), and this finding correlated with lesion volume (R = 0.44, P = .0004) but not brain atrophy (R = -0.16). Enlarged perivascular spaces increased in number with time in all regions, and the rate of increase did not differ among clinical groups. CONCLUSIONS: Enlarged perivascular spaces at the level of the basal ganglia are associated with greater neuroinflammatory burden, and the rate of enlargement appears constant in patients with relapsing-remitting disease phenotypes.


Subject(s)
Glymphatic System , Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Basal Ganglia/diagnostic imaging , Basal Ganglia/pathology , Brain/diagnostic imaging , Brain/pathology , Glymphatic System/diagnostic imaging , Glymphatic System/pathology , Humans , Magnetic Resonance Imaging/methods , Multiple Sclerosis/pathology , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/pathology
2.
Vaccine ; 39(5): 797-804, 2021 01 29.
Article in English | MEDLINE | ID: mdl-33408013

ABSTRACT

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.


Subject(s)
Pandemics , Vaccines , Australia/epidemiology , Pandemics/prevention & control , Resource Allocation , Trust
3.
Sci Total Environ ; 722: 137745, 2020 Jun 20.
Article in English | MEDLINE | ID: mdl-32199357

ABSTRACT

Many lakes undergo anthropogenically driven eutrophication and pollution leading to decreased water and sediment quality. These effects can enhance seasonally changing lake redox conditions that may concentrate potentially toxic elements. Here we report the results of a multi-method geochemical and sediment microfabric analysis applied to reconstruct the history of cultural eutrophication and pollution of the North and South Basins of Windermere, UK. Eutrophication developed from the mid-19th to the earliest 20th centuries. Enhanced lake productivity is indicated by increased sedimentary δ13C, and increased pollution by a higher concentration of metals (Pb, Hg, and As) in the sediment, likely enhanced by incorporation and adsorption to settling diatom aggregates, preserved as sedimentary laminae. In the South Basin, increasing sediment δ15N values occur in step with Zn, Hg, and Cu, linking metal enrichment to isotopically heavy nitrate (N) from anthropogenic sources. From around 1930, decreases in Mn and Fe-rich laminae indicate reduced deep-water ventilation, whereas periods of sediment anoxia increased, being most severe in the deeper North Basin. Strongly reducing sediment conditions promoted Fe and Mn reduction and Pb-bearing barite formation, hitherto only described from toxic mine wastes and contaminated soils. From 1980 there was an increase in indicators of bottom water oxygenation, although not to before 1930. But in the South Basin, the continued impacts of sewage are indicated by elevated sediment δ15N. Imaging and X-ray microanalysis using scanning electron microscopy has shown seasonal-scale redox mineralisation of Mn, Fe, and Ba related to intermittent sediment anoxia. Elevated concentrations of these metals and As also occur in the surficial sediment and provide evidence for dynamic redox mobilisation of potentially toxic elements to the lake water. Concentrations of As (up to 80 ppm), exceed international Sediment Quality Standards. This process may become more prevalent in the future with climate change driving lengthened summer stratification.

4.
Mult Scler Relat Disord ; 38: 101522, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31785491

ABSTRACT

BACKGROUND: The assessment of cognitive information processing speed (IPS) is complicated in MS, with altered performance on tests such as the Symbol Digit Modalities Test (SDMT) potentially representing changes not only within cognitive networks but in the initial sensorial transmission of information to cognitive networks, and/or efferent transmission of the motor response. OBJECTIVE: We aimed to isolate and characterise cognitive IPS deficits in MS using ocular motor tasks; a prosaccade task (used to assess and control for sensorial and motor IPS) which was then used to adjust performance on the Simon task (cognitive IPS). METHODS: All participants (22 MS patients with early disease, 22 healthy controls) completed the ocular motor tasks and the SDMT. The Simon task assessed cognitive IPS by manipulating the relationship between a stimulus location and its associated response direction. Two trial types were interleaved: (1) congruent, where stimulus location = response direction; or (2) incongruent, where stimulus location ≠ response direction. RESULTS MS patients did not perform differently to controls on the SDMT. For OM tasks, when sensorial and motor IPS was controlled, MS patients had significantly slower cognitive IPS (incongruent trials only) and poorer conflict resolution. SDMT performance did not correlate with slower cognitive IPS in MS patients, highlighting the limitation of using SDMT performance to interpret cognitive IPS changes in patients with MS. CONCLUSION: Cognitive IPS deficits in MS patients are dissociable from changes in other processing stages, manifesting as impaired conflict resolution between automatic and non-automatic processes. Importantly, these results raise concerns about the SDMT as an accurate measure of cognitive IPS in MS.


Subject(s)
Cognitive Dysfunction/physiopathology , Executive Function/physiology , Eye Movements/physiology , Multiple Sclerosis, Relapsing-Remitting/physiopathology , Psychomotor Performance/physiology , Reaction Time/physiology , Space Perception/physiology , Visual Perception/physiology , Adult , Cognitive Dysfunction/etiology , Conflict, Psychological , Eye Movement Measurements , Female , Humans , Male , Middle Aged , Multiple Sclerosis, Relapsing-Remitting/complications , Neuropsychological Tests
5.
BMC Med Res Methodol ; 19(1): 178, 2019 08 20.
Article in English | MEDLINE | ID: mdl-31429718

ABSTRACT

BACKGROUND: Current methods for assessing strength of evidence prioritize the contributions of randomized controlled trials (RCTs). The objective of this study was to characterize strength of evidence (SOE) tools in recent use, identify their application to lifestyle interventions for improved longevity, vitality, or successful aging, and to assess implications of the findings. METHODS: The search strategy was created in PubMed and modified as needed for four additional databases: Embase, AnthropologyPlus, PsycINFO, and Ageline, supplemented by manual searching. Systematic reviews and meta-analyses of intervention trials or observational studies relevant to lifestyle intervention were included if they used a specified SOE tool. Data was collected for each SOE tool. Conditions necessary for assigning the highest SOE grading and treatment of prospective cohort studies within each SOE rating framework were summarized. The expert panel convened to discuss the implications of findings for assessing evidence in the domain of lifestyle medicine. RESULTS AND CONCLUSIONS: A total of 15 unique tools were identified. Ten were tools developed and used by governmental agencies or other equivalent professional bodies and were applicable in a variety of settings. Of these 10, four require consistent results from RCTs of high quality to award the highest rating of evidence. Most SOE tools include prospective cohort studies only to note their secondary contribution to overall SOE as compared to RCTs. We developed a new construct, Hierarchies of Evidence Applied to Lifestyle Medicine (HEALM), to illustrate the feasibility of a tool based on the specific contributions of diverse research methods to understanding lifetime effects of health behaviors. Assessment of evidence relevant to lifestyle medicine requires a potential adaptation of SOE approaches when outcomes and/or exposures obviate exclusive or preferential reliance on RCTs. This systematic review was registered with the International Prospective Register of Systematic Reviews, PROSPERO [CRD42018082148].


Subject(s)
Biomedical Research/methods , Evidence-Based Medicine/methods , Health Behavior , Life Style , Randomized Controlled Trials as Topic/methods , Research Design , Aged , Aging , Biomedical Research/classification , Evidence-Based Medicine/classification , Humans , Randomized Controlled Trials as Topic/classification
6.
Ann Plast Surg ; 83(3): 258-263, 2019 09.
Article in English | MEDLINE | ID: mdl-31021838

ABSTRACT

BACKGROUND: Anabolic-androgenic steroids (AAS) are widely implicated in gynecomastia development. Surgery is the definitive treatment for cases persisting after cessation of AAS use. Currently, the relevance of AAS use to the surgical approach of gynecomastia has not been well explored. This study aims to compare patient characteristics, surgical outcomes, and surgical management of gynecomastia correction in AAS users versus nonusers. METHODS: A retrospective cohort study was performed with patients who underwent bilateral gynecomastia reduction surgery between January 2005 and August 2015 by a single surgeon at an academic hospital. Demographic data, AAS usage details, operative documentation, and follow-up outcomes were reviewed. RESULTS: A total of 964 cases were reviewed. Eleven percent (n = 105) of the patients had a history of AAS use. Compared with non-AAS users, AAS users were older at time of gynecomastia onset (15 years vs 13 years, P < 0.001) and surgery (28 years vs 25 years, P < 0.001). The AAS users had higher body mass index (27.3 kg/m vs 25.7 kg/m, P < 0.001) and a greater proportion of patients self-identified as bodybuilders (40.0% vs 22.4%, P = 0.002). Although no difference was found in the excised bilateral mastectomy volume (92.1 cm vs 76.4 cm, P = 0.20), The AAS users had significantly less lipoaspirate fat volume (250 mL vs 300 mL, P = 0.005). No difference was found in total complication rates. However, AAS users had significantly more revision mastectomy surgeries (3.8% vs 1.1%; P = 0.02). CONCLUSIONS: The unique breast composition of AAS users necessitates a surgical approach with meticulous intraoperative hemostasis and careful glandular excision to minimize recurrence and achieve comparable low complication rates.


Subject(s)
Gynecomastia/chemically induced , Gynecomastia/surgery , Mastectomy , Testosterone Congeners/adverse effects , Adult , Cohort Studies , Gynecomastia/epidemiology , Humans , Male , Prevalence , Retrospective Studies , Treatment Outcome , Young Adult
7.
Mult Scler J Exp Transl Clin ; 4(2): 2055217318771781, 2018.
Article in English | MEDLINE | ID: mdl-29707228

ABSTRACT

BACKGROUND: It has been suggested that switching ability might not be affected in multiple sclerosis (MS) as previously thought; however, whether this is true under more 'real-world' conditions when asymmetry in task difficulty is present has not been ascertained. OBJECTIVE: The objective of this paper is to examine the impact of task difficulty asymmetry on task switching ability in MS. METHOD: An ocular motor (OM) paradigm that interleaves the simple task of looking towards a target (prosaccade, PS) with the cognitively more difficult task of looking away from a target (antisaccade, PS) was used. Two switching conditions: (1) PS switch cost, switching to a simple task from a difficult task (PS switch), relative to performing two simple tasks concurrently (PS repeat); (2) AS switch cost, switching to a difficult task from a simple task (AS switch) relative to performing two difficult tasks concurrently (AS repeat). Forty-five relapsing-remitting MS patients and 30 control individuals were compared. RESULTS: Controls and patients produced a similar magnitude PS switch cost, suggesting that task difficulty asymmetry does not detrimentally impact MS patients when transitioning from a more difficult task to a simpler task. However, MS patients alone found switching from the simpler PS trial to the more difficult AS trial easier (shorter latency and reduced error) than performing two AS trials consecutively (AS switch benefit). Further, MS patients performed significantly more errors than controls when required to repeat the same trial consecutively. CONCLUSION: MS patients appear to find the maintenance of task-relevant processes difficult not switching per se, with deficits exacerbated under increased attentional demands.

8.
Clin Radiol ; 73(9): 782-791, 2018 09.
Article in English | MEDLINE | ID: mdl-29801658

ABSTRACT

AIM: To identify combined positron-emission tomography (PET)/magnetic resonance imaging (MRI)-based radiomics as a surrogate biomarker of intratumour disease risk for molecular subtype ccA and ccB in patients with primary clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: PET/MRI data were analysed retrospectively from eight patients. One hundred and sixty-eight radiomics features for each tumour sampling based on the regionally sampled tumours with 23 specimens were extracted. Sparse partial least squares discriminant analysis (SPLS-DA) was applied to feature screening on high-throughput radiomics features and project the selected features to low-dimensional intrinsic latent components as radiomics signatures. In addition, multilevel omics datasets were leveraged to explore the complementing information and elevate the discriminative ability. RESULTS: The correct classification rate (CCR) for molecular subtype classification by SPLS-DA using only radiomics features was 86.96% with permutation test p=7×10-4. When multi-omics datasets including mRNA, microvascular density, and clinical parameters from each specimen were combined with radiomics features to refine the model of SPLS-DA, the best CCR was 95.65% with permutation test, p<10-4; however, even in the case of generating the classification based on transcription features, which is the reference standard, there is roughly 10% classification ambiguity. Thus, this classification level (86.96-95.65%) of the proposed method represents the discriminating level that is consistent with reality. CONCLUSION: Featured with high accuracy, an integrated multi-omics model of PET/MRI-based radiomics could be the first non-invasive investigation for disease risk stratification and guidance of treatment in patients with primary ccRCC.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Multimodal Imaging , Biomarkers, Tumor , Contrast Media , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Neoplasm Grading , Neoplasm Staging , Positron-Emission Tomography , Retrospective Studies
9.
Western Pac Surveill Response J ; 9(5 Suppl 1): 18-26, 2018.
Article in English | MEDLINE | ID: mdl-31832250

ABSTRACT

Surveillance for influenza-like illness (ILI) and laboratory-confirmed influenza in Victoria, Australia is undertaken jointly by the Victorian Infectious Diseases Reference Laboratory and the Victorian Government Department of Health and Human Services from May to October each year. Surveillance data comprise notifiable laboratory-confirmed influenza and ILI reporting from from two sources - a general practice sentinel surveillance programme and a locum service. The magnitude of the 2017 influenza season was high in Victoria with widespread circulation of influenza type A(H3N2), which peaked in September. A record number of laboratory-confirmed influenza cases were notified, and the proportion of ILI cases to total consultations from both the general practice and locum service were higher than previous years. Notified cases of influenza A were older than influenza B cases with 25% compared to 17% aged more than 65 years, respectively. The proportion of swabs that were positive for influenza peaked at 58%. Antigenic characterization suggested a good match between the circulating and vaccine strains of influenza A(H3N2). Most of the increases observed in notified cases of laboratory-confirmed influenza in recent years in Victoria have been attributed to increases in testing. However, that cases of ILI also increased in Victoria in 2017 is suggestive that 2017 was a relatively severe season. The dominance of influenza type A(H3N2), the extended duration of elevated activity, and a potential phylogenetic mismatch of vaccine to circulating strains are likely to have contributed to the relative severity of the 2017 season. Victoria is Australia's second most populous state and is the mainland's southernmost state. It has a temperate climate with an influenza season usually occurring in the cooler months between May and October. The Victorian Infectious Diseases Reference Laboratory (VIDRL), in partnership with the Victorian Government Department of Health and Human Services (DHHS), coordinates influenza-like illness (ILI) and laboratory-confirmed influenza surveillance in Victoria. There are three data sources included in the influenza surveillance system.


Subject(s)
Influenza A Virus, H3N2 Subtype/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Clinical Laboratory Techniques/statistics & numerical data , Disease Outbreaks/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Influenza, Human/diagnosis , Male , Middle Aged , Population Surveillance/methods , Vaccination Coverage/statistics & numerical data , Victoria/epidemiology , Young Adult
10.
Transl Psychiatry ; 6(12): e984, 2016 12 13.
Article in English | MEDLINE | ID: mdl-27959330

ABSTRACT

DNA methylation of the Fragile X mental retardation 1 (FMR1) exon 1/intron 1 boundary has been associated with executive dysfunction in female carriers of a FMR1 premutation (PM: 55-199 CGG repeats), whereas neuroanatomical changes have been associated with executive dysfunction in PM males. To our knowledge, this study for the first time examined the inter-relationships between executive function, neuroanatomical structure and molecular measures (DNA methylation and FMR1 mRNA levels in blood) in PM and control (<44 CGG repeats) females. In the PM group, FMR1 intron 1 methylation was positively associated with executive function and cortical thickness in middle and superior frontal gyri, and left inferior parietal gyrus. By contrast, in the control group, FMR1 intron 1 methylation was negatively associated with cortical thickness of the left middle frontal gyrus and superior frontal gyri. No significant associations were revealed for either group between FMR1 mRNA and neuroanatomical structure or executive function. In the PM group, the lack of any significant association between FMR1 mRNA levels and phenotypic measures found in this study suggests that either FMR1 expression is not well conserved between tissues, or that FMR1 intron 1 methylation is linked to neuroanatomical and cognitive phenotype in PM females via a different mechanism.


Subject(s)
Brain/pathology , DNA Methylation/genetics , Executive Function/physiology , Fragile X Syndrome/genetics , Fragile X Syndrome/pathology , Adult , DNA Mutational Analysis , Exons/genetics , Female , Fragile X Syndrome/complications , Fragile X Syndrome/diagnosis , Humans , Introns/genetics , Magnetic Resonance Imaging , Middle Aged , Neuropsychological Tests , Phenotype , Statistics as Topic , Trinucleotide Repeats/genetics , Young Adult
11.
PLoS One ; 11(6): e0157418, 2016.
Article in English | MEDLINE | ID: mdl-27309958

ABSTRACT

PURPOSE: To report identification of a COL17A1 mutation in a family with a corneal dystrophy previously mapped to chromosome 10q23-q24. METHODS: Whole-exome sequencing was performed on DNA samples from five affected family members and two unrelated, unaffected individuals. Identified variants were filtered for those that were: located in the linked interval on chromosome 10q23-q24; novel or rare (minor allele frequency ≤0.01); heterozygous; present in all affected individuals and not in controls; and present in genes that encode proteins expressed in human corneal epithelial cells (reads per kilobase per million ≥1). Sanger sequencing of identified variants (SNVs) was performed in additional family members. In silico analysis was used to predict the functional impact of non-synonymous variants. RESULTS: Three SNVs located in two genes were identified that met the filtering criteria: one rare synonymous c.3156C>T variant in the collagen, type XVII, alpha I (COL17A1) gene; and two rare variants, one synonymous and one missense, in the dynamin binding protein (DNMBP) gene. Sanger sequencing of additional family members determined that only the COL17A1 variant segregates with the affected phenotype. In silico analysis predicts that the missense variant in DNMBP would be tolerated. CONCLUSIONS: The corneal dystrophy mapped to chromosome 10q23-q24 is associated with the c.3156C>T variant in COL17A1. As this variant has recently been identified in five other families with early onset recurrent corneal erosions, and has been shown in vitro to introduce a cryptic splice donor site, this dystrophy is likely caused by aberrant splicing of COL17A1 and should be classified as epithelial recurrent erosion dystrophy.


Subject(s)
Alternative Splicing , Autoantigens/genetics , Chromosomes, Human, Pair 10/chemistry , Corneal Dystrophies, Hereditary/genetics , Epithelium, Corneal/metabolism , Epithelium, Corneal/pathology , Mutation , Non-Fibrillar Collagens/genetics , Aged , Alleles , Autoantigens/metabolism , Case-Control Studies , Chromosome Mapping , Corneal Dystrophies, Hereditary/diagnosis , Corneal Dystrophies, Hereditary/metabolism , Corneal Dystrophies, Hereditary/pathology , Cytoskeletal Proteins/genetics , Epithelial Cells/metabolism , Epithelial Cells/pathology , Exome , Female , Gene Expression , Gene Frequency , Genes, Dominant , Genome-Wide Association Study , Heterozygote , Humans , Male , Non-Fibrillar Collagens/metabolism , Pedigree , Phenotype , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Collagen Type XVII
13.
Epidemiol Infect ; 144(11): 2317-28, 2016 08.
Article in English | MEDLINE | ID: mdl-27125368

ABSTRACT

Data were pooled from three Australian sentinel general practice influenza surveillance networks to estimate Australia-wide influenza vaccine coverage and effectiveness against community presentations for laboratory-confirmed influenza for the 2012, 2013 and 2014 seasons. Patients presenting with influenza-like illness at participating GP practices were swabbed and tested for influenza. The vaccination odds of patients testing positive were compared with patients testing negative to estimate influenza vaccine effectiveness (VE) by logistic regression, adjusting for age group, week of presentation and network. Pooling of data across Australia increased the sample size for estimation from a minimum of 684 to 3,683 in 2012, from 314 to 2,042 in 2013 and from 497 to 3,074 in 2014. Overall VE was 38% [95% confidence interval (CI) 24-49] in 2012, 60% (95% CI 45-70) in 2013 and 44% (95% CI 31-55) in 2014. For A(H1N1)pdm09 VE was 54% (95% CI-28 to 83) in 2012, 59% (95% CI 33-74) in 2013 and 55% (95% CI 39-67) in 2014. For A(H3N2), VE was 30% (95% CI 14-44) in 2012, 67% (95% CI 39-82) in 2013 and 26% (95% CI 1-45) in 2014. For influenza B, VE was stable across years at 56% (95% CI 37-70) in 2012, 57% (95% CI 30-73) in 2013 and 54% (95% CI 21-73) in 2014. Overall VE against influenza was low in 2012 and 2014 when A(H3N2) was the dominant strain and the vaccine was poorly matched. In contrast, overall VE was higher in 2013 when A(H1N1)pdm09 dominated and the vaccine was a better match. Pooling data can increase the sample available and enable more precise subtype- and age group-specific estimates, but limitations remain.


Subject(s)
Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Influenza B virus/immunology , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adolescent , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Influenza Vaccines/administration & dosage , Influenza, Human/epidemiology , Logistic Models , Male , Middle Aged , Retrospective Studies , Seasons , Sentinel Surveillance , Vaccination , Young Adult
14.
Genes Brain Behav ; 13(4): 385-93, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24521091

ABSTRACT

This study examines implicit sequence learning impairments that may indicate at-risk cerebellar profiles proposed to underlie some aspects of subtle cognitive and affective dysfunctions found among female fragile X mental retardation 1 (FMR1) premutation (PM)-carriers. A total of 34 female PM-carriers and 33 age- and intelligence-matched controls completed an implicit symbolically primed serial reaction time task (SRTT) previously shown to be sensitive to cerebellar involvement. Implicit learning scores indicated a preservation of learning in both groups; however, PM-carriers demonstrated poorer learning through significantly elevated response latencies overall and at each specific block within the symbolic SRTT. Group comparisons also revealed a core deficit in response inhibition, alongside elevated inattentive symptoms in female PM-carriers. Finally, strong and significant associations were observed between poor symbolic SRTT performance and executive, visuospatial and affective deficits in the PM-carrier group. These associations remained strong even after controlling motor speed, and were not observed in age- and intelligence quotient-matched participants. The findings implicate cerebellar non-motor networks subserving the implicit sequencing of responses in cognitive-affective phenotypes previously observed in female PM-carriers. We contend that symbolic SRTT performance may offer clinical utility in future pharmaceutical interventions in female PM-carriers.


Subject(s)
Alleles , Cerebellar Diseases/genetics , Cognition , Fragile X Mental Retardation Protein/genetics , Heterozygote , Learning , Adult , Attention , Case-Control Studies , Cerebellar Diseases/physiopathology , Executive Function , Female , Fragile X Syndrome/genetics , Fragile X Syndrome/physiopathology , Humans , Middle Aged , Reaction Time
15.
Int Urogynecol J ; 25(5): 631-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24337585

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Shortened perineal body (PB) is associated with an increased risk of ultrasound-detected obstetric anal sphincter tear. The objective was to determine if shortened perineal body length (<3 cm) is a risk factor for ultrasound-detected anal sphincter tear at first delivery. METHODS: Pregnant nulliparous women were recruited over 18 months. At 35-37 weeks' gestation and 6 weeks' postpartum perineal body length (PB) was measured and subjects completed quality of life questionnaires. Primary outcome was ultrasound-diagnosed anal sphincter tear at 6 weeks postpartum. Secondary outcomes were also assessed. A priori power analysis determined that 70 subjects were needed to detect a difference in anal sphincter tear based on a PB cut-off of 3 cm. RESULTS: Seventy-three subjects completed the study. Mode of delivery was 69.9% spontaneous vaginal, 15.1% operative vaginal, and 15.1% labored cesarean. There were 25 anal sphincter abnormalities (34.2%) seen on ultrasound: 11 (15.1%) internal or external sphincter tears, 3 (4.1%) internal sphincter atrophy, 6 (8.2%) external sphincter thinning, and 7 (9.6%) external sphincter scarring. Only the 11 sphincter tears qualified as abnormal for the primary outcome. In the vaginal delivery group 16.4% (10 out of 61) had a sphincter tear, compared with 8.3% (1 out of 12) in the labored cesarean group (p = 0.68). Women with PB < 3 had a significantly higher rate of ultrasound-diagnosed anal sphincter tear (40.0% vs 11.1%, p = 0.038). When comparing women with and without sphincter tear, there was a significant difference in mean antepartum PB (3.1 vs 3.7 cm, p = 0.043). CONCLUSIONS: A shortened perineal body length in primiparous women is associated with an increased risk of anal sphincter tear at the time of first delivery.


Subject(s)
Anal Canal/injuries , Lacerations/etiology , Obstetric Labor Complications/etiology , Perineum/anatomy & histology , Perineum/diagnostic imaging , Adult , Female , Humans , Parity , Pregnancy , Prospective Studies , Risk Factors , Ultrasonography
16.
Support Care Cancer ; 22(2): 435-44, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24091719

ABSTRACT

BACKGROUND: Cancer caregiving has emerged as a dominant focus of research in recent years. A striking feature of this vast amount of literature is that it is static, examining certain points of the cancer trajectory, mostly the diagnosis and palliative care. Only The Cancer Caregiving Experience Model conceptualised the caregiving experience and explored the conceptual implications of cancer family caregiving research. AIM: The data from this paper aim to empirically support the Cancer Caregiving Experience model, by exploring the cancer caregiving experience longitudinally. METHODS: Semi-structured interviews with 53 caregivers were carried out at patient's diagnosis (T1), 3 months (T2), 6 months (T3) and 12 months (T4) post diagnosis. RESULTS: Analysis of 139 interviews generated four themes that reflected a complex and dynamic process. The themes that mapped those of the model were "Primary stressors", "Secondary stressors", "Appraisal", "Cognitive-Behavioural responses" and "Health and Well Being". CONCLUSIONS: The study adds empirical support to The Cancer Caregiving Experience Model and confirms that different primary and secondary stressors influence how the caregivers perceive the caregiving demands, the coping mechanisms they employ and their health and well being during the cancer trajectory. Access to support services should be offered to all the caregivers from as early as the diagnosis period and take into account their specific needs.


Subject(s)
Caregivers/psychology , Models, Psychological , Neoplasms/psychology , Neoplasms/therapy , Stress, Psychological/etiology , Stress, Psychological/psychology , Adaptation, Psychological , Aged , Female , Health Services Needs and Demand , Humans , Longitudinal Studies , Male , Middle Aged , Palliative Care/methods , Palliative Care/psychology , Qualitative Research
17.
Neuroscience ; 243: 76-87, 2013 Jul 23.
Article in English | MEDLINE | ID: mdl-23562581

ABSTRACT

Autism and Asperger's disorder (AD) are neurodevelopmental disorders primarily characterized by deficits in social interaction and communication, however motor coordination deficits are increasingly recognized as a prevalent feature of these conditions. Although it has been proposed that children with autism and AD may have difficulty utilizing visual feedback during motor learning tasks, this has not been directly examined. Significantly, changes within the cerebellum, which is implicated in motor learning, are known to be more pronounced in autism compared to AD. We used the classic double-step saccade adaptation paradigm, known to depend on cerebellar integrity, to investigate differences in motor learning and the use of visual feedback in children aged 9-14 years with high-functioning autism (HFA; IQ>80; n=10) and AD (n=13). Performance was compared to age and IQ matched typically developing children (n=12). Both HFA and AD groups successfully adapted the gain of their saccades in response to perceived visual error, however the time course for adaptation was prolonged in the HFA group. While a shift in saccade dynamics typically occurs during adaptation, we revealed aberrant changes in both HFA and AD groups. This study contributes to a growing body of evidence centrally implicating the cerebellum in ocular motor dysfunction in autism. Specifically, these findings collectively imply functional impairment of the cerebellar network and its inflow and outflow tracts that underpin saccade adaptation, with greater disturbance in HFA compared to AD.


Subject(s)
Adaptation, Physiological/physiology , Asperger Syndrome/physiopathology , Autistic Disorder/physiopathology , Cerebellum/physiopathology , Saccades/physiology , Adolescent , Child , Humans , Learning/physiology
19.
Euro Surveill ; 17(11)2012 Mar 15.
Article in English | MEDLINE | ID: mdl-22449867

ABSTRACT

We used a sentinel general practitioner (GP) network to conduct surveillance for laboratory-confirmed influenza amongst patients presenting with influenza-like illness (ILI) in Victoria, Australia in 2011. The test negative variation of the case control study design was used to estimate effectiveness for seasonal trivalent influenza vaccine. Cases and controls were ILI patients that tested positive and negative for influenza, respectively. Vaccination status was recorded by GPs and vaccine effectiveness (VE) was calculated as (1-adjusted odds ratio)x100%. There were 529 patients included in the study, of which 29% were influenza positive. Twelve percent of study participants were reported as vaccinated, 6% of cases and 15% of controls. Adjusted VE against all influenza was 56%, but not statistically significant. There was generally little variation in VE estimates when stratified by virus type and subtype, which is consistent with good matches between circulating strains and the vaccine strains. The VE was higher among adults of working age than among children.


Subject(s)
Disease Outbreaks/prevention & control , Disease Outbreaks/statistics & numerical data , General Practice/statistics & numerical data , Influenza Vaccines/therapeutic use , Influenza, Human/epidemiology , Influenza, Human/prevention & control , Population Surveillance/methods , Adolescent , Adult , Aged , Aged, 80 and over , Australia/epidemiology , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Treatment Outcome , Urban Population/statistics & numerical data , Young Adult
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