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Some of the greatest successes in infectious disease control rest on empirically grounded models of human and livestock infections. In contrast, disease control in wildlife has not always been as successful. Timely translation of knowledge into proposed management actions remains a challenge in several wildlife disease systems, one of which is pneumonia management in bighorn sheep throughout the North American West. Although pneumonia was recognised as a major impediment to bighorn sheep conservation >80 years ago, a series of challenges stymied the management decision-making process. Despite past obstacles, recent advances from long-term, intensive studies of marked individual sheep have motivated new interest in research-driven strategies for disease management in this system. The system provides an unusual opportunity to study an emerging pathogen disproportionately impacting immature animals through infections that originate from asymptomatically infected adult hosts. We tell the story of bighorn sheep pneumonia, emphasising the obstacles that historically hindered decision-making, the biological or logistical constraints underlying each decision point, and the particular empirical insights that clarified each constraint.
The diet of most adults is low in fish and, therefore, provides limited quantities of the long-chain, omega-3 fatty acids (LCn-3FAs), eicosapentaenoic and docosahexaenoic acids (EPA, DHA). Since these compounds serve important roles in the brain, we sought to determine if healthy adults with low-LCn-3FA consumption would exhibit improvements in neuropsychological performance and parallel changes in brain morphology following repletion through fish oil supplementation.
In a randomized, controlled trial, 271 mid-life adults (30–54 years of age, 118 men, 153 women) consuming ⩽300 mg/day of LCn-3FAs received 18 weeks of supplementation with fish oil capsules (1400 mg/day of EPA and DHA) or matching placebo. All participants completed a neuropsychological test battery examining four cognitive domains: psychomotor speed, executive function, learning/episodic memory, and fluid intelligence. A subset of 122 underwent neuroimaging before and after supplementation to measure whole-brain and subcortical tissue volumes.
Capsule adherence was over 95%, participant blinding was verified, and red blood cell EPA and DHA levels increased as expected. Supplementation did not affect performance in any of the four cognitive domains. Exploratory analyses revealed that, compared to placebo, fish oil supplementation improved executive function in participants with low-baseline DHA levels. No changes were observed in any indicator of brain morphology.
In healthy mid-life adults reporting low-dietary intake, supplementation with LCn-3FAs in moderate dose for moderate duration did not affect neuropsychological performance or brain morphology. Whether salutary effects occur in individuals with particularly low-DHA exposure requires further study.
Powerful synergies between phosphonate, zinc oxide, and acrylamido-tert-butyl-sulfonate (ATBS) copolymer chemical additives render superior performance in a high-temperature retarder system for oil well grade Portland cement. The phosphonate retarder and ATBS-based retarders establish a two-tiered strength development where amorphous C-S-H converts to crystalline dicalcium silicate hydrate (C2SH) in the first (low compressive strength) tier prior to the reaction of Portlandite with quartz. The three additive retarder system can be tuned with nanosilica to eliminate the two-tiered strength development effect leading to a smooth transition from the cement in the slurry form directly to its highest compressive strength.
In the current manuscript we discuss the response of dynamic metallogels that display reversion to the liquid state when exposed to phosphines. The metallogels are formed through the condensation of formaldehyde and poly(alkyloxide)amines in polar aprotic solvents. The gel formation can be catalyzed with trivalent metals (Al(III and Fe(III)) with concomitant enhanced dynamism (gelation/degelation). When various phosphines are introduced, the metallogel is irreversibly liquefied. This process adds a new vector for controlling the bulk properties of this class of materials. Here, we explore the mechanism in detail for the reaction of tris(carboxyethyl)phosphine with N,N,N-triethoxylethyl-1,3,5-hexahydro-1,3,5-triazine (HEHT, 1) a stable derivative of the active hexahydrotriazine (HT) core in dimethylformamide in the presence or absence of Al(III). Additionally, density functional theory is used on the model N,N,N-trimethyl system (MHT, 2) to estimate reaction parameters and predict nuclear magnetic resonance spectra.
Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disease and is caused by heterozygous germ-line mutations in either PKD1 (85%) or PKD2 (15%). It is characterised by the formation of numerous fluid-filled renal cysts and leads to adult-onset kidney failure in ~50% of patients by 60 years. Kidney cysts in ADPKD are focal and sporadic, arising from the clonal proliferation of collecting-duct principal cells, but in only 1–2% of nephrons for reasons that are not clear. Previous studies have demonstrated that further postnatal reductions in PKD1 (or PKD2) dose are required for kidney cyst formation, but the exact triggering factors are not clear. A growing body of evidence suggests that DNA damage, and activation of the DNA damage response pathway, are altered in ciliopathies. The aims of this review are to: (i) analyse the evidence linking DNA damage and renal cyst formation in ADPKD; (ii) evaluate the advantages and disadvantages of biomarkers to assess DNA damage in ADPKD and finally, (iii) evaluate the potential effects of current clinical treatments on modifying DNA damage in ADPKD. These studies will address the significance of DNA damage and may lead to a new therapeutic approach in ADPKD.
A robust biomedical informatics infrastructure is essential for academic health centers engaged in translational research. There are no templates for what such an infrastructure encompasses or how it is funded. An informatics workgroup within the Clinical and Translational Science Awards network conducted an analysis to identify the scope, governance, and funding of this infrastructure. After we identified the essential components of an informatics infrastructure, we surveyed informatics leaders at network institutions about the governance and sustainability of the different components. Results from 42 survey respondents showed significant variations in governance and sustainability; however, some trends also emerged. Core informatics components such as electronic data capture systems, electronic health records data repositories, and related tools had mixed models of funding including, fee-for-service, extramural grants, and institutional support. Several key components such as regulatory systems (e.g., electronic Institutional Review Board [IRB] systems, grants, and contracts), security systems, data warehouses, and clinical trials management systems were overwhelmingly supported as institutional infrastructure. The findings highlighted in this report are worth noting for academic health centers and funding agencies involved in planning current and future informatics infrastructure, which provides the foundation for a robust, data-driven clinical and translational research program.
n-3 Fatty acids are associated with better cardiovascular and cognitive health. However, the concentration of EPA, DPA and DHA in different plasma lipid pools differs and factors influencing this heterogeneity are poorly understood. Our aim was to evaluate the association of oily fish intake, sex, age, BMI and APOE genotype with concentrations of EPA, DPA and DHA in plasma phosphatidylcholine (PC), NEFA, cholesteryl esters (CE) and TAG. Healthy adults (148 male, 158 female, age 20–71 years) were recruited according to APOE genotype, sex and age. The fatty acid composition was determined by GC. Oily fish intake was positively associated with EPA in PC, CE and TAG, DPA in TAG, and DHA in all fractions (P≤0·008). There was a positive association between age and EPA in PC, CE and TAG, DPA in NEFA and CE, and DHA in PC and CE (P≤0·034). DPA was higher in TAG in males than females (P<0·001). There was a positive association between BMI and DPA and DHA in TAG (P<0·006 and 0·02, respectively). APOE genotype×sex interactions were observed: the APOE4 allele associated with higher EPA in males (P=0·002), and there was also evidence for higher DPA and DHA (P≤0·032). In conclusion, EPA, DPA and DHA in plasma lipids are associated with oily fish intake, sex, age, BMI and APOE genotype. Such insights may be used to better understand the link between plasma fatty acid profiles and dietary exposure and may influence intake recommendations across population subgroups.
Earlier reports have summarized crop yield losses throughout various North American regions if weeds were left uncontrolled. Offered here is a report from the current WSSA Weed Loss Committee on potential yield losses due to weeds based on data collected from various regions of the United States and Canada. Dry bean yield loss estimates were made by comparing dry bean yield in the weedy control with plots that had >95% weed control from research studies conducted in dry bean growing regions of the United States and Canada over a 10-year period (2007 to 2016). Results from these field studies showed that dry bean growers in Idaho, Michigan, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Ontario, and Manitoba would potentially lose an average of 50%, 31%, 36%, 59%, 94%, 31%, 71%, 56%, and 71% of their dry bean yield, respectively. This equates to a monetary loss of US $36, 40, 6, 56, 421, 2, 18, 44, and 44 million, respectively, if the best agronomic practices are used without any weed management tactics. Based on 2016 census data, at an average yield loss of 71.4% for North America due to uncontrolled weeds, dry bean production in the United States and Canada would be reduced by 941,000,000 and 184,000,000 kg, valued at approximately US $622 and US $100 million, respectively. This study documents the dramatic yield and monetary losses in dry beans due to weed interference and the importance of continued funding for weed management research to minimize dry bean yield losses.
Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.
The interaction of radio frequency waves with charged particles in a magnetized plasma is usually described by the quasilinear operator that was originally formulated by Kennel & Engelmann (Phys. Fluids, vol. 9, 1966, pp. 2377–2388). In their formulation the plasma is assumed to be homogenous and embedded in a uniform magnetic field. In tokamak plasmas the Kennel–Engelmann operator does not capture the magnetic drifts of the particles that are inherent to the non-uniform magnetic field. To overcome this deficiency a combined drift and gyrokinetic derivation is employed to derive the quasilinear operator for radio frequency heating and current drive in a tokamak with magnetic drifts retained. The derivation requires retaining the magnetic moment to higher order in both the unperturbed and perturbed kinetic equations. The formal prescription for determining the perturbed distribution function then follows a novel procedure in which two non-resonant terms must be evaluated explicitly. The systematic analysis leads to a diffusion equation that is compact and completely expressed in terms of the drift kinetic variables. The equation is not transit averaged, and satisfies the entropy principle, while retaining the full poloidal angle variation without resorting to Fourier decomposition. As the diffusion equation is in physical variables, it can be implemented in any computational code. In the Kennel–Engelmann formalism, the wave–particle resonant delta function is either for the Landau resonance or the Doppler shifted cyclotron resonance. In the combined gyro and drift kinetic approach, a term related to the magnetic drift modifies the resonance condition.
Depressive patients can present with complex and different symptom patterns in clinical care. Of these, some may report patterns that are inconsistent with typical patterns of depressive symptoms. This study aimed to evaluate the validity of person-fit statistics to identify inconsistent symptom reports and to assess the clinical usefulness of providing clinicians with person-fit score feedback during depression assessment.
Inconsistent symptom reports on the Inventory of Depressive Symptomatology Self-Report (IDS-SR) were investigated quantitatively with person-fit statistics for both intake and follow-up measurements in the Groningen University Center of Psychiatry (n = 2036). Subsequently, to investigate the causes and clinical usefulness of on-the-fly person-fit alerts, qualitative follow-up assessments were conducted with three psychiatrists about 20 of their patients that were randomly selected.
Inconsistent symptom reports at intake (12.3%) were predominantly characterized by reporting of severe symptoms (e.g. psychomotor slowing) without mild symptoms (e.g. irritability). Person-fit scores at intake and follow-up were positively correlated (r = 0.45). Qualitative interviews with psychiatrists resulted in an explanation for the inconsistent response behavior (e.g. complex comorbidity, somatic complaints, and neurological abnormalities) for 19 of 20 patients. Psychiatrists indicated that if provided directly after the assessment, a person-fit alert would have led to new insights in 60%, and be reason for discussion with the patient in 75% of the cases.
Providing clinicians with automated feedback when inconsistent symptom reports occur is informative and can be used to support clinical decision-making.
Limbic white matter pathways link emotion, cognition, and behavior and are potentially malleable to the influences of traumatic events throughout development. However, the impact of interactions between childhood and later life trauma on limbic white matter pathways has yet to be examined. Here, we examined whether childhood maltreatment moderated the effect of combat exposure on diffusion tensor imaging measures within a sample of military veterans (N = 28). We examined five limbic tracts of interest: two components of the cingulum (cingulum, cingulate gyrus, and cingulum hippocampus [CGH]), the uncinate fasciculus, the fornix/stria terminalis, and the anterior limb of the internal capsule. Using effect sizes, clinically meaningful moderator effects were found only within the CGH. Greater combat exposure was associated with decreased CGH fractional anisotropy (overall structural integrity) and increased CGH radial diffusivity (perpendicular water diffusivity) among individuals with more severe childhood maltreatment. Our findings provide preliminary evidence of the moderating effect of childhood maltreatment on the relationship between combat exposure and CGH structural integrity. These differences in CGH structural integrity could have maladaptive implications for emotion and memory, as well as provide a potential mechanism by which childhood maltreatment induces vulnerability to later life trauma exposure.
Objectives: Preterm children demonstrate deficits in executive functions including inhibition, working memory, and cognitive flexibility; however, their goal setting abilities (planning, organization, strategic reasoning) remain unclear. This study compared goal setting abilities between very preterm (VP: <30 weeks/<1250 grams) and term born controls during late childhood. Additionally, early risk factors (neonatal brain abnormalities, medical complications, and sex) were examined in relationship to goal setting outcomes within the VP group. Methods: Participants included 177 VP and 61 full-term born control children aged 13 years. Goal setting was assessed using several measures of planning, organization, and strategic reasoning. Parents also completed the Behavior Rating Inventory of Executive Function. Regression models were performed to compare groups, with secondary analyses adjusting for potential confounders (sex and social risk), and excluding children with major neurosensory impairment and/or IQ<70. Within the VP group, regression models were performed to examine the relationship between brain abnormalities, medical complications, and sex, on goal setting scores. Results: The VP group demonstrated a clear pattern of impairment and inefficiency across goal setting measures, consistent with parental report, compared with their full-term born peers. Within the VP group, moderate/severe brain abnormalities on neonatal MRI predicted adverse goal setting outcomes at 13. Conclusions: Goal setting difficulties are a significant area of concern in VP children during late childhood. These difficulties are associated with neonatal brain abnormalities, and are likely to have functional consequences academically, socially and vocationally. (JINS, 2018, 24, 372–381)
Background: The evidence regarding whether co-morbid obsessive compulsive personality disorder (OCPD) is associated with treatment outcomes in obsessive compulsive disorder (OCD) is mixed, with some research indicating that OCPD is associated with poorer response, and some showing that it is associated with improved response. Aims: We sought to explore the role of OCPD diagnosis and the personality domain of conscientiousness on treatment outcomes for exposure and response prevention for OCD. Method: The impact of co-morbid OCPD and conscientiousness on treatment outcomes was examined in a clinical sample of 46 participants with OCD. Results: OCPD diagnosis and scores on conscientiousness were not associated with poorer post-treatment OCD severity, as indexed by Yale-Brown Obsessive Compulsive Scale (YBOCS) scores, although the relative sample size of OCPD was small and thus generalizability is limited. Conclusion: This study found no evidence that OCPD or conscientiousness were associated with treatment outcomes for OCD. Further research with larger clinical samples is required.
Most individuals whose growth was restricted before birth undergo accelerated or catch-up neonatal growth. This is an independent risk factor for later metabolic disease, but the underlying mechanisms are poorly understood. This study aimed to test the hypothesis that natural and experimentally induced in utero growth restriction increase neonatal appetite and milk intake. Control (CON) and placentally restricted (PR) ewes carrying multiple fetuses delivered naturally at term. Outcomes were compared between CON (n=14) and PR (n=12) progeny and within twin lamb pairs. Lamb milk intake and feeding behaviour and ewe milk composition were determined using a modified weigh-suckle-weigh procedure on days 15 and 23. PR lambs tended to have lower birth weights than CON (−15%, P=0.052). Neonatal growth rates were similar in CON and PR, whilst heavier twins grew faster in absolute but not fractional terms than their co-twins. At day 23, milk protein content was higher in PR than CON ewes (P=0.038). At day 15, PR lambs had fewer suckling bouts than CON lambs and in females light twins had more suckling attempts than their heavier co-twins. Birth weight differences between twins positively predicted differences in milk intakes. Lactational constraint and natural prenatal growth restriction in twins may explain the similar milk intakes in CON and PR. Within twin comparisons support the hypothesis that prenatal constraint increases lamb appetite, although this did not increase milk intake. We suggest that future mechanistic studies of catch-up growth be performed in singletons and be powered to assess effects in each sex.