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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.
To describe the characteristics of people in Central and Eastern Sydney (CES), NSW, who had a General Practice Management Plan (GPMP) and claimed for at least one private allied health service item; and to examine if allied health service use results in less hospitalisations over a five-year period.
The number of people living with chronic health conditions is increasing in Australia. The Chronic Disease Management programme was introduced to the Medicare Benefits Schedule (MBS) to provide a more structured approach to managing patients with chronic conditions and complex care needs. The programme supports general practitioners claiming up to one GPMP and one Team Care Arrangement every year, and the patient additionally claiming for up to five private allied health services visits.
A prospective longitudinal study was conducted. The sample consisted of 5771 participants in CES who had a GPMP within a two-year health service utilisation baseline period (2007–2009). The analysis used the 45 and Up Study questionnaire data linked to the MBS, hospitalisation, death and emergency department data for the period 2006–2014.
Of the eligible participants, 43% (2460) had at least one allied health service item claim in the subsequent 12 months. Allied health services were reported as physiotherapy, podiatry and other allied health services. The highest rates of allied health service use were among participants aged 85 years and over (49%). After controlling for confounding factors, a significant difference was found between having claimed for five or more physiotherapy services and emergency admissions (HR: 0.83; 95% CI: 0.72–0.95) and potentially preventable hospitalisations (HR: 0.79; 95% CI: 0.64–0.96) in the subsequent five years. Use of allied health service items was well targeted towards those with chronic and complex care needs, and use of physiotherapy services was associated with less avoidable hospitalisations.
We studied the association between chlorhexidine gluconate (CHG) concentration on skin and resistant bacterial bioburden. CHG was almost always detected on the skin, and detection of methicillin-resistant Staphylococcus aureus, carbapenem-resistant Enterobacteriaceae, and vancomycin-resistant Enterococcus on skin sites was infrequent. However, we found no correlation between CHG concentration and bacterial bioburden.
Iron deficiency is common in pregnant and lactating women and is associated with reduced cognitive development of the offspring. Since iron affects lipid metabolism, the availability of fatty acids, particularly the polyunsaturated fatty acids required for early neural development, was investigated in the offspring of female rats fed iron-deficient diets during gestation and lactation. Subsequent to the dams giving birth, one group of iron-deficient dams was recuperated by feeding an iron-replete diet. Dams and neonates were killed on postnatal days 1, 3 and 10, and the fatty acid composition of brain and stomach contents was assessed by gas chromatography. Changes in the fatty acid profile on day 3 became more pronounced on day 10 with a decrease in the proportion of saturated fatty acids and a compensatory increase in monounsaturated fatty acids. Long-chain polyunsaturated fatty acids in the n-6 family were reduced, but there was no change in the n-3 family. The fatty acid profiles of neonatal brain and stomach contents were similar, suggesting that the change in milk composition may be related to the changes in the neonatal brain. When the dams were fed an iron-sufficient diet at birth, the effects of iron deficiency on the fatty acid composition of lipids in both dam’s milk and neonates’ brains were reduced. This study showed an interaction between maternal iron status and fatty acid composition of the offspring’s brain and suggests that these effects can be reduced by iron repletion of the dam’s diet at birth.
In electron beams where space charge plays an important role in the beam transport, the beams’ transverse and longitudinal properties will become coupled. One example of this is the transverse–longitudinal correlation produced in a current-modulated beam generated in a DC electron gun, formed through the competition between the time-dependent radial space charge force and the time-independent radial focusing force. This correlation will cause both the slice radius and divergence of the beam extracted from the gun to depend on the slice current. Here we consider the transport of such a beam in a linearly tapered solenoid focusing channel. Transport performance was generally improved with longer taper lengths, minimal initial correlation between slice divergence and slice current, and moderate degrees of initial correlation between initial slice radius and slice current. Performance was also generally improved with lower slice emittances, although surprisingly transport was improved by slightly increasing the assumed slice emittance in certain limited circumstances.
Individuals experiencing different medical conditions, as well as healthy volunteers, may often be interested in trial participation, and researchers similarly need to find participants to advance medical knowledge. The ResearchMatch (RM) Trials Today clinical trial searching tool leverages clinicaltrials.gov data to enable potential participants to look for trial opportunities relevant to their situation. To facilitate expanded use of this tool, we undertook a national digital public awareness campaign to increase awareness of Trials Today among members of the general public.
The awareness campaign promoted Trials Today using Facebook and digital banner messages in 2017, encompassing nine cities across the USA. The digital strategy was complemented by print media in several outlets. We employed descriptive statistics to summarize campaign metrics and site usage data during the campaign.
The campaign was successful in increasing visits to Trials Today, with 142,303 sessions logged during its run, as compared to pre-campaign data indicating 104,688 total sessions during the entire 2-year period since the site’s inception. The city-specific click-through rate for all digital impressions, combining Facebook and banner messaging, ranged from 0.50% to 1.09%, resulting in a cost-per-click range of $0.69–$1.15. In addition, visitors conducted 29,697 searches and viewed individual trial records 173,512 times.
The public awareness campaign was successful in increasing use of the RM Trials Today clinical trial searching tool. Our findings support the value of digital media messaging as a cost-effective vehicle for promoting clinical trial awareness, especially for chronic ailments.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.
The value of decolonization as a strategy for preventing methicillin-resistantStaphylococcus aureus (MRSA) in the neonatal intensive care unit (NICU) remains to be determined.
After adding decolonization to further reduce MRSA transmission in our NICU, we conducted this retrospective review to evaluate its effectiveness.
The review included patients who were admitted to our NICU between April 2015 and June 2018 and were eligible for decolonization including twice daily intranasal mupirocin and daily chlorhexidine gluconate bathing over 5 consecutive days. Patients were considered successfully decolonized if 3 subsequent MRSA screenings conducted at 1-week intervals were negative. The MRSA acquisition rate (AR) was calculated as hospital-acquired (HA) MRSA per 1,000 patient days (PD) and was used to measure the effectiveness of the decolonization.
Of the 151 MRSA patients being reviewed, 78 (51.6%) were HA-MRSA, resulting in an overall AR of 1.27 per 1,000 PD. Between April 2015 and February 2016, when only the decolonization was added, the AR was 2.38 per 1,000 PD. Between March 2016 and June 2018 after unit added a technician dedicated to the cleaning of reusable equipment, the AR decreased significantly to 0.92 per 1,000 PD (P < .05). Of the 78 patients who were started on the decolonization, 49 (62.8%) completed the protocol, 11 (14.1%) remained colonized, and 13 (16.7%) were recolonized prior to NICU discharge.
In a NICU with comprehensive MRSA prevention measures in place, enhancing the cleaning of reusable equipment, not decolonization, led to significant reduction of MRSA transmission.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
We used a survey to characterize contemporary infection prevention and antibiotic stewardship program practices across 64 healthcare facilities, and we compared these findings to those of a similar 2013 survey. Notable findings include decreased frequency of active surveillance for methicillin-resistant Staphylococcus aureus, frequent active surveillance for carbapenem-resistant Enterobacteriaceae, and increased support for antibiotic stewardship programs.
This article examines the history of immigrant business proprietors in England and Wales between 1851 and 1911. The newly available electronic version of the Census (I-CeM) allows all business proprietors in each Census year to be identified, and provides birthplace information that allows entrepreneurs from different countries to be compared to each other and to business proprietors born in the United Kingdom. Immigrant populations had higher rates of business proprietorship than the English and Welsh-born population. This article argues that this was caused by labour market structure and demography rather than cultural differences between English- and foreign-born business proprietors.
This is a copy of the slides presented at the meeting but not formally written up for the volume.
As in vivo cellular imaging becomes the necessary norm for understanding cancer and other diseases, new non-toxic nanoprobes are going to be required to replace the high quality cadmium based nanoprobes in use today. We are developing less toxic probes based on two types of luminescent ceramic nanoparticles: naturally occurring fluorescent (NOF) mimics and Ln-based ceramic oxide materials. The NOF minerals of interest and that have demonstrated initial luminosity of sufficient brightness for use in cellular studies that include sphalerite, scheelite, manganoan and perovskite nanoparticles. For Ln-based materials we have shown that Ln-doped zincite will also luminesce enough to allow for quantification in cellular activity. Once formed, these probes are functionalized such that they can be delivered to desired cellular targets. Probe derivatization has focused on surface capping with functionalized poly(ethyleneglycol) molecules/lipids to yield water soluble NCs and polyarginine-based transporters for transmembrane delivery. The probes are being evaluated for their luminescent properties, as well as their non-toxicity and ability to report on cell-signaling events with various cell lines using multi-spectral, confocal microscopy, and other techniques. Preliminary interdisciplinary studies have validated the basic approaches for the synthesis of NOF nanoprobes and the bio-delivery and imaging of nanoparticles. Work to optimize the design, delivery, and imaging of these new nanoprobes is expected to achieve the NIH directed goal of increasing in the sensitivity and specificity of molecular probes for imaging. Details of the synthesis, functionalization and biological imaging using these probes will be presented. This work partially supported by the United States Department of Energy under contract number DE-AC04-94AL85000. Sandia is a multi-program laboratory operated by Sandia Corporation, a Lockheed-Martin Company, for the United States Department of Energy and by the National Institutes of health through the NIH Roadmap for Medical Research, Grant #1 R21 EB005365-01. Information on this RFA (Innovation in Molecular Imaging Probes) can be found at http://grants.nih.gov/grants/guide/rfa-files/RFA-RM-04-021.html.
Less than half of stool samples from people symptomatic with infectious intestinal disease (IID) will identify a causative organism. A secondary data analysis was undertaken to explore whether symptomology alone could be used to make inferences about causative organisms. Data were utilised from the Second Study of Infectious Intestinal Disease in the Community. A total of 844 cases were analysed. Few symptoms differentiated individual pathogens, but grouping pathogens together showed that viral IID was more likely when symptom onset was in winter (odds ratio (OR) 2.08, 95% confidence interval (CI) 1.16–3.75) or spring (OR 1.92, 95% CI 1.11–3.33), the patient was aged under 5 years (OR 3.63, 95% CI 2.24–6.03) and there was loss of appetite (OR 2.19, 95% CI 1.29–3.72). The odds of bacterial IID were higher with diarrhoea in the absence of vomiting (OR 3.54, 95% CI 2.37–5.32), diarrhoea which persisted for >3 days (OR 2.69, 95% CI 1.82–3.99), bloody diarrhoea (OR 4.17, 95% CI 1.63–11.83) and fever (OR 1.67, 95% CI 1.11–2.53). Symptom profiles could be of value to help guide clinicians and public health professionals in the management of IID, in the absence of microbiological confirmation.
We conducted a secondary analysis of data from the National Audit of Psychosis to identify factors associated with use of community treatment orders (CTOs) and assess the quality of care that people on CTOs receive.
Between 1.1 and 20.2% of patients in each trust were being treated on a CTO. Male gender, younger age, greater use of in-patient services, coexisting substance misuse and problems with cognition predicted use of CTOs. Patients on CTOs were more likely to be screened for physical health, have a current care plan, be given contact details for crisis support, and be offered cognitive–behavioural therapy.
CTOs appear to be used as a framework for delivering higher-quality care to people with more complex needs. High levels of variation in the use of CTOs indicate a need for better evidence about the effects of this approach to patient care.
To ascertain opinions regarding etiology and preventability of hospital-onset bacteremia and fungemia (HOB) and perspectives on HOB as a potential outcome measure reflecting quality of infection prevention and hospital care.
Hospital epidemiologists and infection preventionist members of the Society for Healthcare Epidemiology of America (SHEA) Research Network.
A web-based, multiple-choice survey was administered via the SHEA Research Network to 133 hospitals.
A total of 89 surveys were completed (67% response rate). Overall, 60% of respondents defined HOB as a positive blood culture on or after hospital day 3. Central line-associated bloodstream infections and intra-abdominal infections were perceived as the most frequent etiologies. Moreover, 61% thought that most HOB events are preventable, and 54% viewed HOB as a measure reflecting a hospital’s quality of care. Also, 29% of respondents’ hospitals already collect HOB data for internal purposes. Given a choice to publicly report central-line–associated bloodstream infections (CLABSIs) and/or HOB, 57% favored reporting either HOB alone (22%) or in addition to CLABSI (35%) and 34% favored CLABSI alone.
Among the majority of SHEA Research Network respondents, HOB is perceived as preventable, reflective of quality of care, and potentially acceptable as a publicly reported quality metric. Further studies on HOB are needed, including validation as a quality measure, assessment of risk adjustment, and formation of evidence-based bundles and toolkits to facilitate measurement and improvement of HOB rates.