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Identifying persons with HIV (PWH) at increased risk for Alzheimer’s disease (AD) is complicated because memory deficits are common in HIV-associated neurocognitive disorders (HAND) and a defining feature of amnestic mild cognitive impairment (aMCI; a precursor to AD). Recognition memory deficits may be useful in differentiating these etiologies. Therefore, neuroimaging correlates of different memory deficits (i.e., recall, recognition) and their longitudinal trajectories in PWH were examined.
Design:
We examined 92 PWH from the CHARTER Program, ages 45–68, without severe comorbid conditions, who received baseline structural MRI and baseline and longitudinal neuropsychological testing. Linear and logistic regression examined neuroanatomical correlates (i.e., cortical thickness and volumes of regions associated with HAND and/or AD) of memory performance at baseline and multilevel modeling examined neuroanatomical correlates of memory decline (average follow-up = 6.5 years).
Results:
At baseline, thinner pars opercularis cortex was associated with impaired recognition (p = 0.012; p = 0.060 after correcting for multiple comparisons). Worse delayed recall was associated with thinner pars opercularis (p = 0.001) and thinner rostral middle frontal cortex (p = 0.006) cross sectionally even after correcting for multiple comparisons. Delayed recall and recognition were not associated with medial temporal lobe (MTL), basal ganglia, or other prefrontal structures. Recognition impairment was variable over time, and there was little decline in delayed recall. Baseline MTL and prefrontal structures were not associated with delayed recall.
Conclusions:
Episodic memory was associated with prefrontal structures, and MTL and prefrontal structures did not predict memory decline. There was relative stability in memory over time. Findings suggest that episodic memory is more related to frontal structures, rather than encroaching AD pathology, in middle-aged PWH. Additional research should clarify if recognition is useful clinically to differentiate aMCI and HAND.
Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery.
Methods:
Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission.
Results:
Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected.
Conclusions:
Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.
Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.
Participants and Methods:
The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, and
relevant imaging covariates (i.e., intracranial volume or mean cortical thickness).
Results:
APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).
Conclusions:
Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.
To analyze Clostridioides difficile testing in 3 hospitals in central North Carolina to validate previous racial health-disparity findings.
Methods:
We completed a retrospective analysis of inpatient C. difficile tests from 2015 to 2021 at 3 university-affiliated hospitals in North Carolina. We calculated the number of C. difficile tests per 1,000 patient days stratified by race: White, Black, and non-White, non-Black (NWNB). We defined a unique C. difficile test as one that occurred in an inpatient unit with a matching laboratory accession ID and on differing calendar days. Tests were evaluated overall, by hospital, by year, and by positivity rate.
Results:
In total, 35,160 C. difficile tests and 2,571,850 patient days across all 3 hospitals from 2015 to 2021 were analyzed. The median number of C. difficile tests per 1,000 patient days was 13.85 (interquartile range [IQR], 9.88–16.07). Among all C. difficile tests, 5,225 (15%) were positive. White patients were administered more C. difficile tests (14.46 per 1,000 patient days) than Black patients (12.96; P < .0001) or NWNB race patients (10.27; P < .0001). Black patients were administered more tests than NWNB patients (P < .0001). White patients tested positive at a similar rate to Black patients (15% vs 15%; P = .3655) and higher than NWNB individuals (12%; P = .0061), and Black patients tested positive at a higher rate than NWNB patients (P = .0024).
Conclusion:
White patients received more C. difficile tests than Black and NWNB patient groups when controlling for race patient days. Future studies should control for comorbidities and investigate community onset of C. difficile by race and ethnicity.
There is significant interest in developing early passage cell lines with matched normal reference DNA to facilitate a precision medicine approach in assessing drug response. This study aimed to establish early passage cell lines, and perform whole exome sequencing and short tandem repeat profiling on matched normal reference DNA, primary tumour and corresponding cell lines.
Methods
A cell culture based, in vitro study was conducted of patients with primary human papillomavirus positive and human papillomavirus negative tumours.
Results
Four early passage cell lines were established. Two cell lines were human papillomavirus positive, confirmed by sequencing and p16 immunoblotting. Short tandem repeat profiling confirmed that all cell lines were established from their index tumours. Whole exome sequencing revealed that the matched normal reference DNA was critical for accurate mutational analysis: a high rate of false positive mutation calls were excluded (87.6 per cent).
Conclusion
Early passage cell lines were successfully established. Patient-matched reference DNA is important for accurate cell line mutational calls.
This study aimed to examine factors that may have contributed to community disaster resilience following Hurricane Maria in Puerto Rico.
Methods:
In April 2018, qualitative interviews (n = 22) were conducted with stakeholders in 7 Puerto Rican municipalities (9% of total). Transcripts were deductively and inductively coded and analyzed to identify salient topics and themes, then examined according to strategic themes from the Federal Emergency Management Association’s (FEMA) Whole Community Approach.
Results:
Municipal preparedness efforts were coordinated, community-based, leveraged community assets, and prioritized vulnerable populations. Strategies included (1) multi-sectoral coordination and strategic personnel allocation; (2) neighborhood leader designation as support contacts; (3) leveraging of community leader expertise and social networks to protect vulnerable residents; (4) Censuses of at-risk groups, health professionals, and first responders; and (5) outreach for risk communication and locally tailored protective measures. In the context of collapsed telecommunications, communities implemented post-disaster strategies to facilitate communication with the Puerto Rican Government, between local first responders, and to keep residents informed, including the use of: (1) police radios; (2) vehicles with loudspeakers; (3) direct interpersonal communication; and (4) solar-powered Internet radio stations.
Conclusions:
Adaptive capacities and actions of Puerto Rican communities exemplify the importance of local solutions in disasters. Expanded research is recommended to better understand contributors to disaster resilience.
To determine the prevalence of human papillomavirus in paediatric tonsils in Southwestern Ontario, Canada.
Materials and methods
Patients aged 0–18 years undergoing tonsillectomy were recruited. Two specimens (left and right tonsils) were collected from each participant. Tonsillar DNA was analysed using quantitative polymerase chain reaction to determine the presence of human papillomavirus subtypes 6, 11, 16 or 18.
Results
A total of 102 patients, aged 1–18 years (mean age of 5.7 years), were recruited. Ninety-nine surveys were returned. There were 44 females (44.4 per cent) and 55 males (55.6 per cent). Forty patients (40.4 per cent) were firstborn children and 73 (73.7 per cent) were delivered vaginally. Six mothers (6.1 per cent) and one father (1.0 per cent) had prior known human papillomavirus infection, and one mother (1.0 per cent) had a history of cervical cancer. All tonsil specimens were negative for human papillomavirus subtypes 6, 11, 16 and 18.
Conclusion
No human papillomavirus subtypes 6, 11, 16 or 18 were found in paediatric tonsil specimens from Southwestern Ontario.
Prenatal hormones have been proposed as key factors impacting child development as well as long-term health and disease. Digit ratio (the ratio of the lengths of the second to fourth digits; 2D:4D) has been proposed as a sexually dimorphic, noninvasive marker of prenatal androgen exposure that can be reliably measured in children and adults. To date, few longitudinal pregnancy cohort studies have examined childhood digit ratio in relation to other relevant measures including prenatal hormones and androgen-sensitive outcomes. To augment the current literature on this topic, we measured right-hand digit ratio in 4-year-old children participating in The Infant Development and the Environment Study, a multicenter longitudinal cohort study that has been following mother–child dyads since the first trimester of pregnancy (n = 321). We assessed sex differences in digit ratio and fit multivariable linear regression models to examine digit ratio in relation to: (1) child sex; (2) maternal sex steroid hormone concentrations in early pregnancy; (3) newborn anogenital distance, another proposed measure of sensitivity to prenatal androgens; and (4) gender-typical play behavior as measured by the Preschool Activities Inventory (PSAI) at age 4. We observed no sex difference in digit ratio; the mean 2D:4D was 0.97 ± 0.05 mm in both sexes. Furthermore, digit ratio was not associated with maternal sex steroid concentrations in early pregnancy, anogenital distance in either sex, or PSAI scores in either sex in covariate-adjusted models. In conclusion, we observed no evidence that early childhood digit ratio was associated with child sex or hormone-sensitive measures in this cohort.
Herbicide resistance has for decades been an increasing problem of agronomic crops such as corn and soybean. Several weed species have evolved herbicide resistance in turfgrass systems such as golf courses, sports fields, and sod production—particularly biotypes of annual bluegrass and goosegrass. Consequences of herbicide resistance in agronomic cropping systems indicate what could happen in turfgrass if herbicide resistance becomes broader in terms of species, distribution, and mechanisms of action. The turfgrass industry must take action to develop effective resistance management programs while this problem is still relatively small in scope. We propose that lessons learned from a series of national listening sessions conducted by the Herbicide Resistance Education Committee of the Weed Science Society of America to better understand the human dimensions affecting herbicide resistance in crop production provide tremendous insight into what themes to address when developing effective resistance management programs for the turfgrass industry.
Evidence from previous small trials has suggested the effectiveness of early social communication interventions for autism.
Objectives
The Preschool Autism Communication Trial (PACT) investigated the efficacy of such an intervention in the largest psychosocial autism trial to date.
Aims
To provide a stringent test of a pre-school communication intervention for autism.
Methods
152 children with core autism aged 2 years - 4 years 11 months in a 3 site 2 arm single (assessor) blinded randomised controlled trial of the parent-mediated communication-focused intervention added to treatment as usual (TAU) against TAU alone. Primary outcome; severity of autism symptoms (modified social communication algorithm from Autism Diagnostic Observation Schedule-Generic, ADOS-G). Secondary outcomes; blinded measures of parent-child interaction, child language, and adaptation in school.
Results
At 13 month endpoint the treatment resulted in strong improvement in parental synchronous response to child (adjusted between-group effect size 1.22 (95% CI 0.85, 1.59) and child initiations with parent (ES 0.41 (0.08, 0.74) but small effect on autism symptomatology (ADOS-G, ES -0.24 (95% CI -0.59, 0.11) ns). Parents (not blind to allocation) reported strong treatment effects on child language and social adaptation but effects on blinded research assessed language and school adaptation were small.
Conclusions
Addition of the PACT intervention showed clear benefit in improving parent-child dyadic social communication but no substantive benefit over TAU in modifying objectively rated autism symptoms. This attenuation on generalisation from ‘proximal’ intervention effects to wider symptom change in other contexts remains a significant challenge for autism treatment and measurement methodology.
The fetal membranes (FM) are comprised of the amniotic membrane (AM), chorionic membrane (CM), and underlying maternal decidua. Together they provide a barrier towards ascending infection and enable amniotic fluid (AF) homeostasis. Preterm premature rupture of the membranes (PPROM) can occur spontaneously and complicates around 2% of all pregnancies, leading to preterm birth, chorioamnionitis, neonatal sepsis, limb position defects, respiratory distress syndrome, pulmonary hypoplasia, and chronic lung disease. Membrane separation is a common finding after open fetal surgery that leads to iatrogenic PPROM (iPPROM) and intrauterine infection, complicating over 30% of fetal surgeries. The subsequent associated preterm birth compromises the outcome of treatment, reducing the clinical effectiveness of fetal surgery [1]. Spontaneous healing of the membranes does not occur after fetoscopic surgery, leaving a visible defect in the FM (Figure 50.1) that is prone to AF leakage and subsequent iPPROM [2]. To date, there are no clinical solutions to improve healing of the FM after they rupture.
Selective laser sintering methods are workhorses for additively manufacturing polymer-based components. The ease of rapid prototyping also means it is easy to produce illicit components. It is necessary to have a data-calibrated in-situ physical model of the build process in order to predict expected and defective microstructure characteristics that inform component provenance. Toward this end, sintering models are calibrated and characteristics such as component defects are explored. This is accomplished by assimilating multiple data streams, imaging analysis, and computational model predictions in an adaptive Bayesian parameter estimation algorithm. From these data sources, along with a phase-field model, bulk porosity distributions are inferred. Model parameters are constrained to physically-relevant search directions by sensitivity analysis, and then matched to predictions using adaptive sampling. Using this feedback loop, data-constrained estimates of sintering model parameters along with uncertainty bounds are obtained.
Atrial fibrillation or flutter (AFF) patients with renal impairment have poor long-term prognosis, but their emergency department (ED) management has not been described. We investigated the association of renal impairment upon outcomes after rate or rhythm control (RRC) including ED-based adverse events (AE) and treatment failure.
Methods
This cohort study used an electrocardiogram database from two urban centres to identify consecutive AFF patients and reviewed charts to obtain comorbidities, ED management, including RRC, prespecified AE, and treatment failure. Patients were dichotomized into a normal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2) or impaired renal function (“low eGFR”). Primary and secondary outcomes were prespecified AEs and treatment failure, respectively. We calculated 1) adjusted excess AE risk for patients with decreased renal function receiving RRC; and 2) adjusted odds ratio of RRC treatment failure.
Results
Of 1,112 consecutive ED AFF patients, 412 (37.0%) had a low eGFR. Crude AE rates for RRC were 27/238 (11.3%) for patients with normal renal function and 26/103 (25.2%) for patients with low eGFR. For patients with low eGFR receiving RRC, adjusted excess AE risk was 13.7%. (95% CI 1.7 to 25.1%). For patients with low eGFR, adjusted odds ratio for RRC failure was 3.07. (95% CI 1.74 to 5.43)
Conclusions
In this cohort of ED AFF patients receiving RRC, those with low eGFR had significantly increased adjusted excess risk of AE compared with patients with normal renal function. Odds of treatment failure were also significantly increased.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Solitary fibrous tumour is a soft tissue tumour of mesenchymal origin. It was first described in the pleura and has since been reported in many anatomical locations. Thirteen cases in the tongue have hitherto been reported. A positive CD34 result has traditionally been used to confirm the diagnosis, although this is often non-specific to solitary fibrous tumour. To date, nuclear STAT6 expression has not been reported in solitary fibrous tumour of the tongue.
Method:
This paper presents a further four cases of solitary fibrous tumour of the tongue, the largest series to date. Clinical, histopathological and immunohistochemical findings are detailed, including nuclear STAT6 expression.
Results:
All four cases were positive for CD34; two cases showed nuclear expression of STAT6. The tumours were excised completely and there have been no recurrences in at least one year.
Conclusion:
Solitary fibrous tumour should be considered as a differential diagnosis for tongue swellings, with the potential to recur.
‘Cargill 921′, ‘Great Lakes 422′, ‘Northrup King 9410′, ‘Pioneer 3901′, ‘Pioneer 3737′, and ‘Stauffer 5650’ corn hybrids were tested in the greenhouse for imazaquin tolerance. Imazaquin rates that reduced shoot growth 50%, when compared to the untreated hybrid check, ranged from 17 to 50 g/ha. When averaged together, the three most tolerant hybrids (Cargill 921, Pioneer 3901, and Great Lakes 422) were approximately one-half as sensitive to imazaquin as the three least tolerant hybrids (Northrup King 9410, Pioneer 3737, and Stauffer 5650). Studies were conducted to determine if the observed differential tolerance was caused by differences in acetolactate synthase (ALS, EC 4.1.3.18) levels and sensitivity of ALS to imazaquin. Differential imazaquin uptake, translocation, and/or metabolism were also studied as a basis for the tolerance range as was seed size and seedling growth. There were differences among hybrids in the physiological and growth parameters studied; however, these differences did not correlate with imazaquin tolerance. None of the factors studied could alone account for the differences in imazaquin tolerance.
Growing public concern for pesticide residues in drinking water has resulted in tighter federal and state regulations to prevent ground-water contamination. There are many uncertainties in estimating human exposure risk, yet standards are being set to protect human health. In the last several years, drinking water health standards have been developed for a number of pesticides, often at levels of a few μg L−1 or less. Ground-water monitoring studies, first required by the U.S. Environmental Protection Agency in 1984, have now become an integral requirement to support registration of pesticides shown to have leaching potential. Regulators are now faced with deciding the extent to which pesticides can still be used while continuing to meet legal requirements to protect the public and preserve ground-water resources. The implications are that pesticide use may be severely limited in regions with ground-water resources considered especially vulnerable to contamination, dramatically affecting the type of agricultural practices and crops grown in these regions.
Johnsongrass control in the field was greater with fenoxaprop or haloxyfop than with sethoxydim in 1985 and 1986. Johnsongrass control was reduced under field and greenhouse conditions by adding a dimethylamine salt of 2,4-D. Generally, the antagonism was overcome by increasing the rate of fenoxaprop, haloxyfop, or sethoxydim. Sethoxydim showed less antagonism from 2,4-D than did fenoxaprop or haloxyfop in the greenhouse.