Pre-transplant CDKN2A expression in kidney biopsies predicts renal function and is a future component of donor scoring criteria

CDKN2A is a proven and validated biomarker of ageing which acts as an off switch for cell proliferation. We have demonstrated previously that CDKN2A is the most robust and the strongest pre-transplant predictor of post- transplant serum creatinine when compared to “Gold Standard” clinical factors, such as cold ischaemic time and donor chronological age. This report shows that CDKN2A is better than telomere length, the most celebrated biomarker of ageing, as a predictor of post-transplant renal function. It also shows that CDKN2A is as strong a determinant of post-transplant organ function when compared to extended criteria (ECD) kidneys. A multivariate analysis model was able to predict up to 27.1% of eGFR at one year post-transplant (p = 0.008). Significantly, CDKN2A was also able to strongly predict delayed graft function. A pre-transplant donor risk classification system based on CDKN2A and ECD criteria is shown to be feasible and commendable for implementation in the near future

Promyelocytic leukemia nuclear bodies associate with transcriptionally active genomic regions

Cancer Research UK

Understanding the non-pharmacological correlates of self-reported efficacy of antidepressants

Objective: To explore the non-pharmacological correlates of the perceived effectiveness of antidepressants (ADs), thereby enhancing understanding of the mechanisms involved in recovery from depression while taking ADs. Method: An online survey was completed by 1781 New Zealand adults who had taken ADs in the previous 5 years. Results: All 18 psychosocial variables measured were associated with depression reduction, and 16 with improved quality of life (QoL). Logistic regression models revealed that the quality of the relationship with the prescriber was related to both depression reduction and improved QoL. In addition, depression reduction was related to younger age, higher income, being fully informed about ADs by the prescriber, fewer social causal beliefs for depression and not having lost a loved one in the 2 months prior to prescription. Furthermore, both outcome measures were positively related to belief in ‘chemical’ rather than ‘placebo’ effects. Conclusion: There are multiple non-pharmacological processes involved in recovery while taking ADs. Enhancing them, for example focusing on the prescriber–patient relationship and giving more information, may enhance recovery rates, with or without ADs

In situ evaluation of an automated aerial bait delivery system for landscape-scale control of invasive brown treesnakes on Guam

After decades of biodiversity loss and economic burden caused by the brown treesnake invasion on the Pacific island of Guam, relief hovers on the horizon. Previous work by USDA Wildlife Services (WS) and its National Wildlife Research Center (NWRC) demonstrated that brown treesnake numbers in forested habitats can be dramatically suppressed by aerial delivery of dead newborn mouse (DNM) baits treated with 80 mg of acetaminophen. However, manual bait preparation and application is impractical for landscape-scale treatment. WS, NWRC, and the US Department of the Interior have collaborated with Applied Design Corporation to engineer an automated bait manufacturing and delivery system. The core technology is an aerially delivered biodegradable “bait cartridge” designed to tangle in the tree canopy, making the acetaminophen bait available to treesnakes and out of reach of terrestrial non-target organisms. When mounted on a rotary- or fixed-wing airframe, the automated dispensing module (ADM) unit can broadcast 3,600 bait cartridges at a rate of four per second and can treat 30 hectares of forest at a density of 120 acetaminophen baits per hectare within 15 minutes of firing time. We conducted the first in situ evaluation of the ADM in July 2016. Initial acetaminophen bait deployment rates (proper opening of the bait cartridge for canopy entanglement) were low, and mechanism jams were frequent due to internal friction and wind forces; on-site remedial engineering improved these performance measures. Bait cartridge placement and spacing were accurate (average 8.9 m along 9 m swaths) under various flight heights and speeds. Canopy entanglement of properly-deployed acetaminophen baits was high (66.6%). Although only a small proportion (5.9%) of radio transmitter-equipped acetaminophen baits were confirmed to have been taken by brown treesnakes, the baiting density was high enough to make it likely that a significant proportion of brown treesnakes in the area had taken acetaminophen baits. With subsequent improvements in system reliability, the automated bait cartridge manufacturing and delivery system is poised to transition from research and development to operational field implementation. Applications include reduction of brown treesnake numbers around transportation infrastructure and within core habitats for the reintroduction of native birds extirpated by this troublesome invasive predator

In situ evaluation of an automated aerial bait delivery system for landscape-scale control of invasive brown treesnakes on Guam

After decades of biodiversity loss and economic burden caused by the brown treesnake invasion on the Pacific island of Guam, relief hovers on the horizon. Previous work by USDA Wildlife Services (WS) and its National Wildlife Research Center (NWRC) demonstrated that brown treesnake numbers in forested habitats can be dramatically suppressed by aerial delivery of dead newborn mouse (DNM) baits treated with 80 mg of acetaminophen. However, manual bait preparation and application is impractical for landscape-scale treatment. WS, NWRC, and the US Department of the Interior have collaborated with Applied Design Corporation to engineer an automated bait manufacturing and delivery system. The core technology is an aerially delivered biodegradable “bait cartridge” designed to tangle in the tree canopy, making the acetaminophen bait available to treesnakes and out of reach of terrestrial non-target organisms. When mounted on a rotary- or fixed-wing airframe, the automated dispensing module (ADM) unit can broadcast 3,600 bait cartridges at a rate of four per second and can treat 30 hectares of forest at a density of 120 acetaminophen baits per hectare within 15 minutes of firing time. We conducted the first in situ evaluation of the ADM in July 2016. Initial acetaminophen bait deployment rates (proper opening of the bait cartridge for canopy entanglement) were low, and mechanism jams were frequent due to internal friction and wind forces; on-site remedial engineering improved these performance measures. Bait cartridge placement and spacing were accurate (average 8.9 m along 9 m swaths) under various flight heights and speeds. Canopy entanglement of properly-deployed acetaminophen baits was high (66.6%). Although only a small proportion (5.9%) of radio transmitter-equipped acetaminophen baits were confirmed to have been taken by brown treesnakes, the baiting density was high enough to make it likely that a significant proportion of brown treesnakes in the area had taken acetaminophen baits. With subsequent improvements in system reliability, the automated bait cartridge manufacturing and delivery system is poised to transition from research and development to operational field implementation. Applications include reduction of brown treesnake numbers around transportation infrastructure and within core habitats for the reintroduction of native birds extirpated by this troublesome invasive predator

Direct injection liquid chromatography-tandem mass spectrometry as a sensitive and high-throughput method for the quantitative surveillance of antimicrobials in wastewater

Environmental antimicrobial pollution and antimicrobial resistance pose a threat to environmental and human health. Wastewater analysis has been identified as a promising tool for antimicrobial monitoring and the back-estimation of antimicrobial consumption, but current pretreatment methods are tedious and complicated, limiting their scope for high-throughput analysis. A sensitive direct injection method for the quantification of 109 antimicrobials and their metabolites in wastewater samples was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The method was validated for both wastewater influent and effluent in terms of specificity, calibration range, matrix effect, filtration loss, accuracy, precision, limit of detection (LOD), and limit of quantification (LOQ). Most analytes achieved calibration of R2 &gt; 0.99, and the calibration range was from 0.0002 to 150 μg L−1. Recoveries ranged consistently between ~50 % and ~100 % and losses were attributed to sample filtration. Method LOQs were determined as low as 0.0003 μg L−1, and acceptable accuracy (75 %–125 %) and precision (within 25 %) were achieved for &gt;90 % of the analytes. The method was subsequently further assessed using wastewater of raw influent and treated effluent collected from 6 Australian wastewater treatment plants in 2021. In total, 37 analytes were detected in influent and 22 in effluent. Most of them could be quantified at concentrations ranging from 0.0053 to 160 μg L−1, with benzalkonium chloride-C12, amoxicilloic acid, and cephalexin detected at the highest concentrations. The current study provides a straightforward analytical method for antimicrobial monitoring in wastewater with a fast and simple pretreatment procedure.</p

A powerful intervention: general practitioners' use of sickness certification in depression

&lt;b&gt;Background&lt;/b&gt; Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methods&lt;/b&gt; A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt; A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt; GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

&lt;p&gt;&lt;b&gt;Objectives&lt;/b&gt; The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods&lt;/b&gt; A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt; A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions&lt;/b&gt; The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.&lt;/p&gt