Perfect Enough to Sleep? Perfectionism and Actigraphy-Determined Markers of Insomnia.

OBJECTIVES: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism. METHODS: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected. RESULTS: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects (r = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions. CONCLUSIONS: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Nonsense-mediated decay machinery in Plasmodium falciparum is inefficient and non-essential.

Nonsense-mediated decay (NMD) is a conserved mRNA quality control process that eliminates transcripts bearing a premature termination codon. In addition to its role in removing erroneous transcripts, NMD is involved in post-transcriptional regulation of gene expression via programmed intron retention in metazoans. The apicomplexan parasite Plasmodium falciparum shows relatively high levels of intron retention, but it is unclear whether these variant transcripts are functional targets of NMD. In this study, we use CRISPR-Cas9 to disrupt and epitope-tag the P. falciparum orthologs of two core NMD components: PfUPF1 (PF3D7_1005500) and PfUPF2 (PF3D7_0925800). We localize both PfUPF1 and PfUPF2 to puncta within the parasite cytoplasm and show that these proteins interact with each other and other mRNA-binding proteins. Using RNA-seq, we find that although these core NMD orthologs are expressed and interact in P. falciparum, they are not required for degradation of nonsense transcripts. Furthermore, our work suggests that the majority of intron retention in P. falciparum has no functional role and that NMD is not required for parasite growth ex vivo. IMPORTANCE In many organisms, the process of destroying nonsense transcripts is dependent on a small set of highly conserved proteins. We show that in the malaria parasite, these proteins do not impact the abundance of nonsense transcripts. Furthermore, we demonstrate efficient CRISPR-Cas9 editing of the malaria parasite using commercial Cas9 nuclease and synthetic guide RNA, streamlining genomic modifications in this genetically intractable organism.

Recently Acquired Blood-borne Virus Infections in Australian Deceased Organ Donors: Estimation of the Residual Risk of Unexpected Transmission.

Unexpected donor-derived infections of hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV are rare but important potential complications of deceased organ transplantation. The prevalence of recently acquired (yield) infections has not been previously described in a national cohort of Australian deceased organ donors. Donor yield infections are of particularly significance, as they can be used to gain insights in the incidence of disease in the donor pool and in turn, estimate the risk of unexpected disease transmission to recipients. Methods: We conducted a retrospective review of all patients who commenced workup for donation in Australia between 2014 and 2020. Yield cases were defined by having both unreactive serological screening for current or previous infection and reactive nucleic acid testing screening on initial and repeat testing. Incidence was calculated using a yield window estimate and residual risk using the incidence/window period model. Results: The review identified only a single yield infection of HBV in 3724 persons who commenced donation workup. There were no yield cases of HIV or HCV. There were no yield infections in donors with increased viral risk behaviors. The prevalence of HBV, HCV, and HIV was 0.06% (0.01-0.22), 0.00% (0-0.11), and 0.00% (0-0.11), respectively. The residual risk of HBV was estimated to be 0.021% (0.001-0.119). Conclusions: The prevalence of recently acquired HBV, HCV, and HIV in Australians who commence workup for deceased donation is low. This novel application of yield-case-methodology has produced estimates of unexpected disease transmission which are modest, particularly when contrasted with local average waitlist mortality. Supplemental Visual Abstract; http://links.lww.com/TXD/A503.

The impact of inter-observer variation in delineation on robustness of radiomics features in non-small cell lung cancer.

Artificial intelligence and radiomics have the potential to revolutionise cancer prognostication and personalised treatment. Manual outlining of the tumour volume for extraction of radiomics features (RF) is a subjective process. This study investigates robustness of RF to inter-observer variation (IOV) in contouring in lung cancer. We utilised two public imaging datasets: 'NSCLC-Radiomics' and 'NSCLC-Radiomics-Interobserver1' ('Interobserver'). For 'NSCLC-Radiomics', we created an additional set of manual contours for 92 patients, and for 'Interobserver', there were five manual and five semi-automated contours available for 20 patients. Dice coefficients (DC) were calculated for contours. 1113 RF were extracted including shape, first order and texture features. Intraclass correlation coefficient (ICC) was computed to assess robustness of RF to IOV. Cox regression analysis for overall survival (OS) was performed with a previously published radiomics signature. The median DC ranged from 0.81 ('NSCLC-Radiomics') to 0.85 ('Interobserver'-semi-automated). The median ICC for the 'NSCLC-Radiomics', 'Interobserver' (manual) and 'Interobserver' (semi-automated) were 0.90, 0.88 and 0.93 respectively. The ICC varied by feature type and was lower for first order and gray level co-occurrence matrix (GLCM) features. Shape features had a lower median ICC in the 'NSCLC-Radiomics' dataset compared to the 'Interobserver' dataset. Survival analysis showed similar separation of curves for three of four RF apart from 'original_shape_Compactness2', a feature with low ICC (0.61). The majority of RF are robust to IOV, with first order, GLCM and shape features being the least robust. Semi-automated contouring improves feature stability. Decreased robustness of a feature is significant as it may impact upon the features' prognostic capability.

Prevalence of Blood-Borne Viruses and Predictors of Risk in Potential Organ Donors in Australia.

Internationally, the designation of a patient as an increased viral risk organ donor has been associated with lower utilisation rates. The actual prevalence of blood borne viruses in Australian potential organ donors, and the predictive performance of questionnaires administered to stratify this risk, remains unknown. We conducted a retrospective review of all patients who commenced workup for donation on the national database between 2014-2020. The prevalence of HIV, Active HBV and Active HCV in 3650 potential organ donors was 0.16%, 0.9%, and 2.2%, respectively. The behavioural risk profile was assessed in a subset of 3633 patients. Next-of-kin reported increased risk behaviours were associated with an increased prevalence of HCV but not of HIV or HBV (OR 13.8, p < 0.01, OR 0.3. p = 0.42, OR 1.5, p = 0.14). Furthermore, the majority of HIV and HBV infections occurred in potential donors without a disclosed history of increased risk behaviours. In this series, donors had a higher prevalence of HCV, and similar rates of HBV and HIV to the broader community. Behavioural transmission risks were poorly predictive of HIV and HBV. Rather than pre-transplantation behavioural risk screening, routine post-transplant recipient screening may provide a more powerful tool in mitigating the consequences of unexpected viral transmission.

Factors Associated With Discharge Destination in Community-Dwelling Adults Admitted to Acute General Medical Units.

BACKGROUND AND PURPOSE: General medical patients often present to the hospital with medical, social, cognitive, and functional issues that may impact discharge destination. The aim of this study was to investigate the association between patient factors at hospital admission and discharge destination in general medical patients. METHODS: This was a prospective, single-site observational study conducted on the general medical wards at a tertiary hospital. Inpatients admitted to the general medical unit and referred to physical therapy were included. Patients admitted from residential care were excluded. MAIN OUTCOME MEASURES: Data were collected a median of 2 days (interquartile range: 1-3) from hospital admission and included demographics, comorbidities (Charlson Comorbidity Index), premorbid physical function (Blaylock Risk Assessment Screening Score, BRASS), current function (de Morton Mobility Index, DEMMI and Alpha Functional Independence Measure, AlphaFIM), and cognition (Rowland Universal Dementia Assessment Scale, RUDAS). RESULTS: Between July 2016 and August 2017, 417 patients were recruited (53% female, median age: 81 years (interquartile range: 76-86). Of these, 245 patients were discharged directly home; 172 were not discharged home of whom 140 were discharged to a subacute temporary facility providing further opportunity for therapy and discharge planning. Patients discharged directly home had higher functional, mobility, and cognitive scores. Data were partitioned into training, validation, and test sets to provide unbiased estimates of sensitivity, specificity, receiver operating characteristic curve, and area under the curve. Models best associated with discharge were "DEMMI and toilet transfers" (sensitivity 82.1%, specificity 66.2%, area under the curve 83.8%, 95% confidence interval: 76.4-91.2) and "AlphaFIM and walking independence" (sensitivity: 66.7%, specificity: 83.1%, area under the curve: 81.5, 95% confidence interval: 73.2-89.7). CONCLUSION: Two models were created that differentiated between discharge home and not home and had similar statistical measures of validity. Although the models require further validation, clinicians should consider whether identification of patients likely to be discharged home or not home is of greater relevance for their clinical setting.

Ten-year trends in catheter ablation for ventricular tachycardia vs other interventional procedures in Australia.

AIMS: Major technological and procedural advancements have reinvigorated catheter ablation as adjunctive therapy for drug-refractory ventricular tachycardia (VT). We examined temporal trends in VT ablations as compared to other interventional cardiovascular procedures namely, percutaneous coronary intervention (PCI) and atrial fibrillation (AF) ablation in Australia. METHODS AND RESULTS: A retrospective review of procedural numbers for VT ablations, AF ablations, and PCI was performed from 2008/09-2016/17 the Australian Institute of Health, Welfare and Aging (AIHW), and Medicare Australia (MA) databases. Linear regression models were fitted to compare the trends in population-adjusted procedural numbers over the 10-year period. Data from the AIHW and MA sources respectively showed that (a) PCI had a 1.3% (AIHW data P = .15) and 1.8% (MA data P < .001) population-adjusted increment per year, (b) AF ablations had a 12.7% (P < .001) and 11.7% (P < .001) per year population-adjusted increment, and (c) VT ablations showed an 18% (P < .001) and 12.7% (P < .001) per year population-adjusted increment. Growth of PCI was increasing at a lower rate than AF ablations (P < .001 for both AIHW and MA sources). Growth of VT ablation was significantly higher than AF ablations and PCI (AIHW: 18% vs 12.7% [P = .004] and 1.3% per year [P < .001]). CONCLUSION: Catheter-based VT ablation has increased significantly in Australia over the last decade, consistent with worldwide trends, and now surpassing all ablation procedures, including AF ablation and PCI for CAD. This data highlight the provision of additional resources to match the increasing demand for VT ablation procedures in Australia.