Association of CAG Repeat Length in the Huntington Gene With Cognitive Performance in Young Adults

Objective:To investigate the relationships between CAG repeat length in the huntingtin gene and cognitive performance in participants above and below the disease threshold for Huntington’s Disease (HD), we performed a cross-sectional analysis of the Enroll-HD database.Methods:We analyzed data from young, developing adults (≤ 30 years) without a history of depression, apathy, or cognitive deficits. We included participants with and without the gene-expansion (CAG ≥ 36) for HD. All participants had to have a Total Functional Capacity Score of 13, a diagnostic confidence level of zero, a total motor score of <10, and be more than 28.6 years from their predicted motor onset. We performed regression analyses to investigate the non-linear relationship between CAG repeat length and various cognitive measures controlling for age, sex, and education level.Results:There were significant positive relationships between CAG repeat length and the Symbol Digit Modalities, Stroop Color Naming, and Stroop Interference Tests. There were significant negative relationships between CAG repeat length and parts A and B of the Trails Making Test (p<0.05) indicating that longer CAG repeat lengths were associated with better performance.Discussion:An increasing number of CAG repeats in the huntingtin gene below disease threshold and low pathological CAG ranges was associated with some improvements in cognitive performance. These findings outline the relationship between CAG repeats within the huntingtin gene and cognitive development.Classification of Evidence:This study provides Class IV evidence that CAG repeat length is positively associated with cognitive function across a spectrum of CAG repeat lengths.

Malaria Data Analysis Using Routine Surveillance Data, Sunyani Municipality, Ghana, 2020

IntroductionMalaria is endemic in Ghana, accounting for about 40% of all OPD diagnosis. Data on malaria is routinely collected as part of the IDSR monthly reporting forms. Sunyani municipality recorded 56,540 malaria cases in 2016 with about 35% of the cases occurring in children under five years of age. We analyzed malaria surveillance data to identify the distribution of malaria cases by person, place and time and determine the timeliness and completeness of malaria report submission in the municipality.MethodsWe analyzed malaria surveillance data in Sunyani municipality reported between 2015 and 2019 from the District Health Management Information System II. We calculated morbidity and mortality rates of cases by person and estimated proportion of cases by sub-districts. We performed trend analysis and calculated disease threshold levels. We presented the findings using tables and figures.ResultsOf 639,361 malaria cases suspected, 93.5% (597,512/639,361) were tested, of which 49.4% (295,458/597,512) was positive. Females accounted for 55.7% (164,436/295,458) of the morbidity. Children < 5 years recorded the highest proportion, 29.9% (88,135/295,458) of cases in the municipality. The case fatality rate was 3.7% (18/484) and 1.4% (7/484) for persons under age five and over age five, respectively. Abesim (6,276.03 per 10,000) recorded the highest number of cases, and the least cases were in New Dormaa (1,890.97 per 10,000). The majority of malaria cases were in May and October of each year. Antwi-krom recorded the highest rates of completeness and timeliness of 41.9% and 40.0% respectively.ConclusionMore females were diagnosed with malaria and children < 5 years recorded the highest proportion of cases in the municipality. Abesim recorded the highest proportion of malaria cases during the period. High patterns of malaria transmissions occurred during months of high rainfalls. None of the sub-districts met the WHO target for timeliness and completeness of report submission. The NMCP should consider interventions such as SMC among children under five, in the Sunyani municipality.

Malaria Data Analysis Using Routine Surveillance Data, Sunyani Municipality, Ghana, 2020

Introduction: Malaria is endemic in Ghana, accounting for about 40% of all OPD diagnosis. Data on malaria is routinely collected as part of the IDSR monthly reporting forms. Sunyani municipality recorded 56,540 malaria cases in 2016 with about 35% of the cases occurring in children under five years of age. We analyzed malaria surveillance data to identify the distribution of malaria cases by person, place and time and determine the timeliness and completeness of malaria report submission in the municipality.Methods: We analyzed malaria surveillance data in Sunyani municipality reported between 2015 and 2019 from the District Health Management Information System II. We calculated morbidity and mortality rates of cases by person and estimated proportion of cases by sub-districts. We performed trend analysis and calculated disease threshold levels. We presented the findings using tables and figures.Results: Of 639,361 malaria cases suspected, 93.5% (597,512/639,361) were tested, of which 49.4% (295,458/597,512) was positive. Females accounted for 55.7% (164,436/295,458) of the morbidity. Children <5 years recorded the highest proportion, 29.9% (88,135/295,458) of cases in the municipality. The case fatality rate was 3.7% (18/484) and 1.4% (7/484) for persons under age five and over age five, respectively. Abesim (6,276.03 per 10,000) recorded the highest number of cases, and the least cases were in New Dormaa (1,890.97 per 10,000). The majority of malaria cases were in May and October of each year. Antwi-krom recorded the highest rates of completeness and timeliness of 41.9% and 40.0% respectively. Conclusion: More females were diagnosed with malaria and children <5 years recorded the highest proportion of cases in the municipality. Abesim recorded the highest proportion of malaria cases during the period. High patterns of malaria transmissions occurred during months of high rainfalls. None of the sub-districts met the WHO target for timeliness and completeness of report submission. The NMCP should consider interventions such as SMC among children under five, in the Sunyani municipality.

Coupled Epidemio-Hydrodynamic Modeling to Understand the Spread of a Deadly Coral Disease in Florida

For the last six years, the Florida Reef Tract (FRT) has been experiencing an outbreak of the Stony Coral Tissue Loss Disease (SCTLD). First reported off the coast of Miami-Dade County in 2014, the SCTLD has since spread throughout the entire FRT with the exception of the Dry Tortugas. However, the causative agent for this outbreak is currently unknown. Here we show how a high-resolution bio-physical model coupled with a modified patch Susceptible-Infectious-Removed epidemic model can characterize the potential causative agent(s) of the disease and its vector. In the present study, the agent is assumed to be transported within composite material (e.g., coral mucus, dying tissues, and/or resuspended sediments) driven by currents and potentially persisting in the water column for extended periods of time. In this framework, our simulations suggest that the SCTLD is likely to be propagated within neutrally buoyant material driven by mean barotropic currents. Calibration of our model parameters with field data shows that corals are diseased within a mean transmission time of 6.45 days, with a basic reproduction number slightly above 1. Furthermore, the propagation speed of the disease through the FRT is shown to occur for a well-defined range of values of a disease threshold, defined as the fraction of diseased corals that causes an exponential growth of the disease in the reef site. Our results present a new connectivity-based approach to understand the spread of the SCTLD through the FRT. Such a method can provide a valuable complement to field observations and lab experiments to support the management of the epidemic as well as the identification of its causative agent.

Host status and disease threshold of Rhizoctonia solani (Kühn (teleomorph: Thanatephorus cucumeris (Frank) Donk), on Chia (Salvia hispanica L.) and its suitability as a rotational crop to (Nicotana tabucum L.)

The study was done following the continued outbreaks of problematic diseases in the production of tobacco (N. tabucum) in Zimbabwe which amongst the problematic ones are Rhizoctonia solani and Fusarium solani. The experiment was conducted at Marondera University of Agriculture Science and Technology in Zimbabwe, aiming to evaluate the suitability of Chia as a rotational crop to tobacco. Chia is a seed oil producing legume crop which is regarded the most suitable in rotation with tobacco at the moment because of its monetary benefit to the farmer hence will encourage crop rotation. An experiment was set up with two trials in three growing seasons arranged in a complete block design. Fusarium solani five treatments were used one control and four other different rates of inoculum 2.5g,3.5g, 5.5g and 7.5g/10ml of Distilled water and Rhizoctonia solani five treatments were used with a control and four other different inoculations rates inoculated at 0.1g, 0.2g, 0.4g and 0.6g/10ml Distilled water. Data collection was based on the disease severity scale and index of Chia, and also histochemical parameters which were hydrogen peroxide content and malonaldehyde content. There was significant (p < 0.05) differences between the different inoculation rates of all the measured parameters under the distinct diseases. Hence Chia cannot be rotated with tobacco even under low levels of disease threshold within the soil, unless proper and intensive management practices are put in place.

Correlation of colposcopy with biopsy in cases of abnormal cervical cytology

Aims: This study aims to find out the role of colposcopy and its correlation with cervical biopsy in detection of pre malignant cervical lesion. Methodology: This is hospital based prospective observational study on 60 cases with abnormal cervical cytology reports conducted in the Department of Obstetrics and Gynecology, PMWH, Thapathali, Kathmandu. Colposcopy guided biopsies were done and findings noted. Results: Among 60 cases enrolled in the study the most common cervical cytology finding was ASCUS, LSIL, HSIL and ASC-H present in 46.6%, 31.6%, 15% and 6.6% respectively. The colposcopy finding among these cases was normal, CIN1, CIN 2 and CIN 3 in 45%, 23.3%, 16.7% and 9% respectively. Among these cases the most common biopsy finding was normal, CIN 1, CIN 2, CIN 3 and squamous cell carcinoma in 55%, 18.3%, 8.3%, 15% and 3.3% respectively. The sensitivity, specificity, positive predictive value and negative predictive value of colposcopy with CIN 1 as disease threshold was calculated to be 80.6%, 93.1%, 81.8% and 92.6% respectively. While evaluating the validity of colposcopy with histopathology, colposcopy seems to make an accurate diagnosis in 75% of cases, overestimating in 15% and underestimating in 8% of cases. Conclusions: There is a good correlation of colposcopy with histopathological diagnosis of cervical cancer. Keywords: colposcopy, cytology, diagnosis, premalignant

Disease threshold for cherry leaf spot incidence on commercial sweet cherry cultivars

The aim of this study was to demonstrate the 10% threshold level for cherry leaf spot incidence on 23 commercial sweet cherry cultivars in two training systems. Twenty three cherry cultivars were evaluated in the two training systems with a spacing of 4 x 1 m and with a spacing of 2 x 5 m. Results showed that leaves of many cultivars were heavily infected, e.g. cultivars (cvs) ’Biggareau Burlat’, ’Sunburst’, while others showed low disease incidence e.g. cvs ’Celeste’ and ’Blaze Star’. According to the 10 % threshold level, cv ’Celeste’ proved to be the most resistant cultivar to leaf infection, while cv ’Münchebergi korai’ exceeded extremely the 10% threshold level. Leaf spot incidence was affected by training system on most cultivars. Thirteen cultivars had less than 10% infection in the 4 x 1 m spacing (i.e. they did not reach the 10% disease threshold level). At the same time, only 3 cultivars showed less than 10% infection in the 5 x 2 m spacing.

Residual Disease Monitoring By High Throughput Sequencing Provides Risk Stratification in Childhood B-ALL and Identifies a Novel Subset of Patients Having Poor Outcome

Background Early response to induction chemotherapy is a significant prognostic factor in the outcome of children with acute lymphoblastic leukemia (ALL). High throughput sequencing (HTS) of rearranged immune receptor (TCR and Ig) genes offers the possibility of a more accurate, sensitive, and standardized approach to determination of early response to therapy.In this study, we investigate the ability of an HTS assay to risk stratify children with B-ALL at the end of induction therapy in comparison with flow cytometry (FC), assess the impact of increased MRD sensitivity on risk group assignment, evaluate the significance of MRD discordance between HTS and FC, and identify a novel subset of patients having an inferior outcome. Methods 619 paired Pretreatment and End of Induction (Day 29) samples from patients with B-ALL enrolled on Children's Oncology Group (COG) clinical trials AALL0331 (standard-risk, SR) and AALL0232 (high-risk, HR) having minimal residual disease (MRD) at Day 29 of less than 0.1% by flow cytometry were assayed by high throughput sequencing of CDR3 regions of IGH and TCRG. Dominant clonal CDR3 sequences in the pretreatment samples were quantitated in the paired Day 29 samples as residual disease of total nucleated cells without knowledge of the FC results. The relationship of residual disease determined by HTS and FC to 5-year event-free and overall survival (EFS and OS) was evaluated using Kaplan-Meier statistics. Results HTS detected a dominant clonal sequence in 93.2% of Pretreatment B-ALL samples, providing an informative cohort of standard-risk (N=282) and high-risk (N=297) patients. Using a threshold of 0.01% on the combined cohort, HTS and FC show identical EFS and OS for MRD positive (77.7% ± 0.04, 91.6% ± 0.03) and negative (92.5% ± 0.02, 96.3% ± 0.01) subsets, see Figure 1. Interestingly, reducing the HTS threshold from 0.01% to 0.0001% results in an improvement in EFS for the HTS MRD positive subset in both standard (80.1% -> 88.2%) and high-risk (75.3% -> 84.8%) patients, likely due to major reductions in the number of patients otherwise scored as MRD negative using the higher threshold of 0.01%(70.9% -> 27.0% SR and 78.5% -> 36.7% HR). This reflects the much more favorable outcome of the large cohort of patients with MRD between 0.0001% and 0.01% compared to those >0.01%. Little improvement in EFS is seen for HTS MRD negative patients with a reduction in MRD threshold. Maximal difference in EFS is achieved at an HTS threshold of 0.01%. Importantly, the subset of SR patients with no detectable residual clonal sequence at any level (19.9% of total) show an excellent EFS (98.1% ± 0.02) and OS (100% ± 0), different from the similar subset of HR patients (30.0% of total) showing less favorable EFS (92.7% ± 0.04) and OS (95.1% ± 0.03). Patients discordant for MRD at a threshold of 0.01%, either HTS+/FC- (N=55) or HTS-/FC+ (N=17), show intermediate EFS compared with concordantly positive or negative patients. Of interest, patients lacking a detectable clonal IgH sequence (N=42) show a significantly inferior EFS (78.5% ± 0.08 vs. 89.3% ± 0.02, p=0.01) but not OS. Conclusions HTS is equivalent to FC in its ability to risk stratify patients with childhood B-ALL at End of Induction therapy using a MRD threshold of 0.01%. Reducing the HTS MRD threshold below 0.01% does not improve risk stratification, but does allow identification of a small subset of MRD negative standard-risk patients virtually certain to be cured with current therapy. Patients discordant for MRD between HTS and FC have an outcome intermediate between that seen for concordant patients. Patients lacking a detectable clonal IgH sequence, presumably representing a more primitive form of leukemia, show a significantly inferior outcome. Figure 1. Equivalence of outcomes by high throughput sequencing and flow cytometry for B-ALL patients at a residual disease threshold of 0.01%. Figure 1. Equivalence of outcomes by high throughput sequencing and flow cytometry for B-ALL patients at a residual disease threshold of 0.01%. Disclosures Wood: Pfizer: Honoraria, Other: Laboratory Services Agreement; Amgen: Honoraria, Other: Laboratory Services Agreement; Seattle Genetics: Honoraria, Other: Laboratory Services Agreement; Juno: Other: Laboratory Services Agreement. Kirsch:Adaptive Biotechnology: Employment. Crossley:Adaptive: Employment, Equity Ownership. Williamson:Adaptive Biotechnology: Employment. Borowitz:HTG Molecular: Consultancy; BD Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; MedImmune: Research Funding. Loh:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding. Robins:Adaptive Biotechnology: Employment.

Psychometric assessment in older people

Psychometrics permits the quantification of cognition, affect and behaviour, thus permitting both the identification of pathology and degree of deviation from normality. These methods have been principally used in older populations to screen affective and cognitive disorders, as an adjunct to the differential diagnosis of different forms of cognitive dysfunction and also to describe and monitor the functional consequences of pathology. The application of psychometric tests in older populations raises several problems, notably the confounding effects of associated pathologies, changing definitions of disease threshold in parallel with advances in medical technology, and inadequate knowledge of normal information processing at higher ages. Computerized assessment, once considered inappropriate in older populations, is now commonly used to standardize administration procedures and tailor testing to individual competency. It has also permitted the more accurate measurement of information processing time, which is important in the diagnosis of many neuropsychiatric disorders.