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Toxoplasma gondii possesses a highly polarized secretory pathway that contains both broadly conserved eukaryotic organelles and unique apicomplexan organelles, which play essential roles in the parasite's lytic cycle. As in other eukaryotes, the T. gondii Golgi apparatus sorts and modifies proteins prior to their distribution to downstream organelles. Many of the typical trafficking factors found involved in these processes are missing from apicomplexan genomes, suggesting that these parasites have evolved unique proteins to fill these roles. Here, we identify a Golgi-localizing protein (ULP1), which is structurally similar to the eukaryotic trafficking factor p115/Uso1. We demonstrate that depletion of ULP1 leads to a dramatic reduction in parasite fitness that is the result of defects in microneme secretion, invasion, replication, and egress. Using ULP1 as bait for TurboID proximity labeling and immunoprecipitation, we identify 11 more Golgi-associated proteins and demonstrate that ULP1 interacts with the T. gondii -conserved oligomeric Golgi (COG) complex. These proteins include both conserved trafficking factors and parasite-specific proteins. Using a conditional knockdown approach, we assess the effect of each of these 11 proteins on parasite fitness. Together, this work reveals a diverse set of T. gondii Golgi-associated proteins that play distinct roles in the secretory pathway. As several of these proteins are absent outside of the Apicomplexa, they represent potential targets for the development of novel therapeutics against these parasites., Importance: Apicomplexan parasites such as Toxoplasma gondii infect a large percentage of the world's population and cause substantial human disease. These widespread pathogens use specialized secretory organelles to infect their host cells, modulate host cell functions, and cause disease. While the functions of the secretory organelles are now better understood, the Golgi apparatus of the parasite remains largely unexplored, particularly regarding parasite-specific innovations that may help direct traffic intracellularly. In this work, we characterize ULP1, a protein that is unique to parasites but shares structural similarity to the eukaryotic trafficking factor p115/Uso1. We show that ULP1 plays an important role in parasite fitness and demonstrate that it interacts with the conserved oligomeric Golgi (COG) complex. We then use ULP1 proximity labeling to identify 11 additional Golgi-associated proteins, which we functionally analyze via conditional knockdown. This work expands our knowledge of the Toxoplasma Golgi apparatus and identifies potential targets for therapeutic intervention., Competing Interests: The authors declare no conflict of interest.

Glia derived secretory factors play diverse roles in supporting the development, physiology, and stress responses of the central nervous system (CNS). Through transcriptomics and imaging analyses, we have identified Obp44a as one of the most abundantly produced secretory proteins from Drosophila CNS glia. Protein structure homology modeling and Nuclear Magnetic Resonance (NMR) experiments reveal Obp44a as a fatty acid binding protein (FABP) with a high affinity towards long-chain fatty acids in both native and oxidized forms. Further analyses demonstrate that Obp44a effectively infiltrates the neuropil, traffics between neuron and glia, and is secreted into hemolymph, acting as a lipid chaperone and scavenger to regulate lipid and redox homeostasis in the developing brain. In agreement with this essential role, deficiency of Obp44a leads to anatomical and behavioral deficits in adult animals and elevated oxidized lipid levels. Collectively, our findings unveil the crucial involvement of a noncanonical lipid chaperone to shuttle fatty acids within and outside the brain, as needed to maintain a healthy brain lipid environment. These findings could inspire the design of novel approaches to restore lipid homeostasis that is dysregulated in CNS diseases.

Biomechanical studies play an important role in understanding the pathophysiology of sleep disorders and providing insights to maintain sleep health. Computational methods facilitate a versatile platform to analyze various biomechanical factors in silico, which would otherwise be difficult through in vivo experiments. The objective of this review is to examine and map the applications of computational biomechanics to sleep-related research topics, including sleep medicine and sleep ergonomics. A systematic search was conducted on PubMed, Scopus, and Web of Science. Research gaps were identified through data synthesis on variants, outcomes, and highlighted features, as well as evidence maps on basic modeling considerations and modeling components of the eligible studies. Twenty-seven studies ( n = 27) were categorized into sleep ergonomics ( n = 2 on pillow; n = 3 on mattress), sleep-related breathing disorders ( n = 19 on obstructive sleep apnea), and sleep-related movement disorders ( n = 3 on sleep bruxism). The effects of pillow height and mattress stiffness on spinal curvature were explored. Stress on the temporomandibular joint, and therefore its disorder, was the primary focus of investigations on sleep bruxism. Using finite element morphometry and fluid-structure interaction, studies on obstructive sleep apnea investigated the effects of anatomical variations, muscle activation of the tongue and soft palate, and gravitational direction on the collapse and blockade of the upper airway, in addition to the airflow pressure distribution. Model validation has been one of the greatest hurdles, while single-subject design and surrogate techniques have led to concerns about external validity. Future research might endeavor to reconstruct patient-specific models with patient-specific loading profiles in a larger cohort. Studies on sleep ergonomics research may pave the way for determining ideal spine curvature, in addition to simulating side-lying sleep postures. Sleep bruxism studies may analyze the accumulated dental damage and wear. Research on OSA treatments using computational approaches warrants further investigation.

The objective of this review was to summarize the applications of sonoelastography in testicular tumor identification and inquire about their test performances. Two authors independently searched English journal articles and full conference papers from CINAHL, Embase, IEEE Xplore ® , PubMed, Scopus, and Web of Science from inception and organized them into a PIRO (patient, index test, reference test, outcome) framework. Eleven studies ( n = 11) were eligible for data synthesis, nine of which ( n = 9) utilized strain elastography and two ( n = 2) employed shear-wave elastography. Meta-analyses were performed on the distinction between neoplasm (tumor) and non-neoplasm (non-tumor) from four study arms and between malignancy and benignity from seven study arms. The pooled sensitivity of classifying malignancy and benignity was 86.0% (95%CI, 79.7% to 90.6%). There was substantial heterogeneity in the classification of neoplasm and non-neoplasm and in the specificity of classifying malignancy and benignity, which could not be addressed by the subgroup analysis of sonoelastography techniques. Heterogeneity might be associated with the high risk of bias and applicability concern, including a wide spectrum of testicular pathologies and verification bias in the reference tests. Key technical obstacles in the index test were manual compression in strain elastography, qualitative observation of non-standardized color codes, and locating the Regions of Interest (ROI), in addition to decisions in feature extractions. Future research may focus on multiparametric sonoelastography using deep learning models and ensemble learning. A decision model on the benefits-risks of surgical exploration (reference test) could also be developed to direct the test-and-treat strategy for testicular tumors.

Using a combination of tight binding molecular dynamics and ab initio molecular dynamics simulations, we study the mechanisms of bombardment-induced decomposition of hydrofluorocarbons (HFCs) physisorbed on silicon nitride for ion energies of ≤35 eV. We propose three key mechanisms by which bombardment-driven HFC decomposition can occur, focusing on the two pathways observed at these low ion energies: "direct decomposition" and "collision assisted surface reactions (CASRs)." Our simulation results clearly demonstrate the importance of the presence of favorable reaction coordinates for enabling CASR, which dominates at lower energies (≈11 eV). At higher energies, direct decomposition becomes more favored. Our work also predicts that the primary decomposition pathways for CH3F and CF4 are CH3F → CH3 + F and CF4 → CF2 + 2F, respectively. The fundamental details of these decomposition pathways and the decomposition products formed under ion bombardment have implications for plasma-enhanced atomic layer etching process design that will be discussed., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Aspiration caused by dysphagia is a prevalent problem that causes serious health consequences and even death. Traditional diagnostic instruments could induce pain, discomfort, nausea, and radiation exposure. The emergence of wearable technology with computer-aided screening might facilitate continuous or frequent assessments to prompt early and effective management. The objectives of this review are to summarize these systems to identify aspiration risks in dysphagic individuals and inquire about their accuracy. Two authors independently searched electronic databases, including CINAHL, Embase, IEEE Xplore ® Digital Library, PubMed, Scopus, and Web of Science (PROSPERO reference number: CRD42023408960). The risk of bias and applicability were assessed using QUADAS-2. Nine (n = 9) articles applied accelerometers and/or acoustic devices to identify aspiration risks in patients with neurodegenerative problems (e.g., dementia, Alzheimer's disease), neurogenic problems (e.g., stroke, brain injury), in addition to some children with congenital abnormalities, using videofluoroscopic swallowing study (VFSS) or fiberoptic endoscopic evaluation of swallowing (FEES) as the reference standard. All studies employed a traditional machine learning approach with a feature extraction process. Support vector machine (SVM) was the most famous machine learning model used. A meta-analysis was conducted to evaluate the classification accuracy and identify risky swallows. Nevertheless, we decided not to conclude the meta-analysis findings (pooled diagnostic odds ratio: 21.5, 95% CI, 2.7-173.6) because studies had unique methodological characteristics and major differences in the set of parameters/thresholds, in addition to the substantial heterogeneity and variations, with sensitivity levels ranging from 21.7% to 90.0% between studies. Small sample sizes could be a critical problem in existing studies (median = 34.5, range 18-449), especially for machine learning models. Only two out of the nine studies had an optimized model with sensitivity over 90%. There is a need to enlarge the sample size for better generalizability and optimize signal processing, segmentation, feature extraction, classifiers, and their combinations to improve the assessment performance. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/), identifier (CRD42023408960)., Competing Interests: Author W-KL was employed by Sports Information and External Affairs Centre, Hong Kong Sports Institute Ltd, Hong Kong, China. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lai, Cheng, Lim, So, Lam, Cheung, Wong and Cheung.)

There is growing, but inconsistent evidence suggesting oestrogen may play a key role in lung cancer development, especially among never-smoking women for whom lung cancer risk factors remain largely elusive. Using the China Kadoorie Biobank, a large-scale prospective cohort with 302 510 women aged 30 to 79 years recruited from 10 regions in China during 2004 to 2008, we assessed the risk of lung cancer death among self-reported never-smoking women who were cancer-free at baseline, in relation to age at menarche, age at menopause, time since menopause, prior use of oral contraceptives (OCP), number of livebirths, breastfeeding and age at first livebirth. Women were followed up to December 31, 2016 with linkage to mortality data. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression, adjusting for key confounders including several socio-demographic, environmental and lifestyle factors. Among 287 408 never-smoking women, 814 died from lung cancer with a median follow-up of 10.3 years. Women who had used OCP within 15 years prior to baseline had a significantly higher hazard of lung cancer death compared with never-users: HR = 1.85 (95% CI: 1.14-3.00) and risk increased by 6% with each additional year of use: HR = 1.06 (1.01-1.10). Among parous women, the hazard of lung cancer death increased by 13% with each single livebirth: HR = 1.13 (1.05-1.23); and among post-menopausal women, the risk increased by 2% with each year since menopause: HR = 1.02 (1.01-1.04). These results suggest that reproductive factors which were proxies for lower endogenous oestrogen level, for example, longer duration of OCP use, could play a role in lung cancer development., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Rationale: Household air pollution and secondhand tobacco smoke are known carcinogens for lung cancer, but large-scale estimates of the relationship with lung cancer mortality are lacking. Objectives: Using the large-scale cohort China Kadoorie Biobank, we prospectively investigated associations between these two risk factors and lung cancer death among never-smokers. Methods: The Biobank recruited 512,715 adults aged 30-79 years from 10 regions in China during 2004-2008. Self-reported never-smoking participants were followed up to December 31, 2016, with linkage to mortality data. Total duration of exposure to household air pollution was calculated from self-reported domestic solid fuel use. Exposure to secondhand tobacco smoke was ascertained using exposure at home and/or other places. Hazard ratios and 95% confidence intervals for associations between these two exposures and lung cancer death were estimated using Cox regression, adjusting for key confounders. Measurements and Main Results: There were 979 lung cancer deaths among 323,794 never-smoking participants without a previous cancer diagnosis during 10.2 years of follow-up. There was a log-linear positive association between exposure to household air pollution and lung cancer death, with a 4% increased risk per 5-year increment of exposure (hazard ratio = 1.04; 95% confidence interval = 1.01-1.06; P trend = 0.0034), and participants with 40.1-50.0 years of exposure had the highest risk compared with the never-exposed (hazard ratio = 1.53; 95% confidence interval = 1.13-2.07). The association was largely consistent across various subgroups. No significant association was found between secondhand smoke and lung cancer death. Conclusions: This cohort study provides new prospective evidence suggesting that domestic solid fuel use is associated with lung cancer death among never-smokers.

Purpose: Lung cancer (LC) in never-smoking individuals would rank as Australia's eighth most deadly cancer, yet risk factors remain uncertain. We investigated demographic, lifestyle and health-related exposures for LC among never-smoking Australians., Methods: Using the prospective 45 and Up Study with 267,153 New South Wales (NSW) residents aged ≥ 45 years at recruitment (2006-2009), we quantified the relationship of 20 potential exposures with LC among cancer-free participants at baseline who self-reported never smoking. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for incident LC were estimated using Cox regression. The NSW Cancer, Lifestyle and Evaluation of Risk (CLEAR) Study, a case-control study including 10,781 NSW residents aged ≥ 18 years (2006-2014), was used to examine 16 potential LC exposures among cancer-free never-smoking participants. Adjusted odds ratios (OR) and 95% CI of LC were estimated using logistic regression., Results: There were 226 LC cases among 132,354 cancer-free 45 and Up Study participants who reported never smoking, with a median follow-up of 5.41 years. The CLEAR Study had 58 LC cases and 1316 cancer-free controls who had never smoked. Analyses of both datasets showed that Asian-born participants had a higher risk of LC than those born elsewhere: cohort, adjusted HR = 2.83 (95% CI 1.64-4.89) and case-control, adjusted OR = 3.78 (1.19-12.05). No significant association with LC was found for other exposures., Conclusion: Our findings support the growing evidence that never-smoking, Asian-born individuals are at higher risk of developing LC than those born elsewhere. Ethnicity could be considered when assessing potential LC risk among never-smoking individuals., (© 2022. The Author(s).)

Introduction: Women tend to survive a lung cancer diagnosis longer than men; however potential drivers of this sex-related disparity remain largely elusive. We quantified factors related to sex differences in lung cancer survival in a large prospective cohort in Australia., Methods: Participants in the 45 and Up Study (recruited 2006-2009) diagnosed with incident lung cancer were followed up to December 2015. Prognostic factors were identified from questionnaire data linked with cancer registrations, hospital inpatient records, emergency department records, and reimbursement records for government-subsidized medical services and prescription medicines. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer death for men versus women were estimated using Cox proportional hazard regression in relation to key prognostic factors alone and jointly., Results: A total of 488 women and 642 men were diagnosed with having lung cancer. Women survived significantly longer (median 1.28 versus 0.77 y; HR for men = 1.43, 95% CI: 1.25-1.64, p < 0.0001). The survival disparity remained when each subgroup of major prognostic factors was evaluated separately, including histologic subtype, stage at diagnosis, treatment received, and smoking status. Multivariable analyses revealed that treatment-related factors explained half of the survival difference, followed by lifestyle and tumor characteristics (explaining 28%, 26%, respectively). After adjusting for all major known prognostic factors, the excess risk for men was reduced by more than 80% (HR = 1.06, 95% CI: 0.96-1.18, p = 0.26)., Conclusions: The sex-related lung cancer survival disparity in this Australian cohort was largely accounted for by known prognostic factors, indicating an opportunity to explore sex differences in treatment preferences, options, and access., (Copyright © 2022 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Lung cancer is the leading cause of cancer-related mortality globally, accounting for 1.8 million deaths in 2020. While the vast majority are caused by tobacco smoking, 15%-25% of all lung cancer cases occur in lifelong never-smokers. The International Agency for Research on Cancer (IARC) has classified multiple agents with sufficient evidence for lung carcinogenesis in humans, which include tobacco smoking, as well as several environmental exposures such as radon, second-hand tobacco smoke, outdoor air pollution, household combustion of coal and several occupational hazards. However, the IARC evaluation had not been stratified based on smoking status, and notably lung cancer in never-smokers (LCINS) has different epidemiological, clinicopathologic and molecular characteristics from lung cancer in ever-smokers. Among several risk factors proposed for the development of LCINS, environmental factors have the most available evidence for their association with LCINS and their roles cannot be overemphasized. Additionally, while initial genetic studies largely focused on lung cancer as a whole, recent studies have also identified genetic risk factors for LCINS. This article presents an overview of several environmental factors associated with LCINS, and some of the emerging evidence for genetic factors associated with LCINS. An increased understanding of the risk factors associated with LCINS not only helps to evaluate a never-smoker's personal risk for lung cancer, but also has important public health implications for the prevention and early detection of the disease. Conclusive evidence on causal associations could inform longer-term policy reform in a range of areas including occupational health and safety, urban design, energy use and particle emissions, and the importance of considering the impacts of second-hand smoke in tobacco control policy., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (Copyright ©2021Chinese Journal of Cancer Research. All rights reserved.)

Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo evidence indicating isoform-specific expression of lipoprotein receptors as a key mechanism for regulating cell-type specific lipid recruitment.

Background: Globally, radon is the leading risk factor for lung cancer in never-smokers (LCINS). In this study, we systematically reviewed and meta-analysed the evidence of the risk of LCINS associated with residential radon exposure., Methods: Medline and Embase databases were searched using predefined inclusion and exclusion criteria to identify relevant studies published from 1 January 1990 to 5 March 2020 focused on never-smokers. We identified four pooled collaborative studies (incorporating data from 24 case-control studies), one case-control study and one cohort study for systematic review. Meta-analysis was performed on the results of the four pooled studies due to different measures of effect and outcome reported in the cohort study and insufficient information reported for the case-control study. In a post hoc analysis, the corresponding risk for ever-smokers was also examined., Results: Risk estimates of lung cancer from residential radon exposure were pooled in the meta-analysis for 2341 never-smoker cases, 8967 never-smoker controls, 9937 ever-smoker cases and 12 463 ever-smoker controls. Adjusted excess relative risks (aERRs) per 100 Bq·m -3 of radon level were 0.15 (95% CI 0.06-0.25) for never-smokers and 0.09 (95% CI 0.03-0.16) for ever-smokers, and the difference between them was statistically insignificant (p=0.32). The aERR per 100 Bq·m -3 was higher for men (0.46; 95% CI 0.15-0.76) than for women (0.09; 95% CI -0.02-0.20) among never-smokers (p=0.027)., Conclusion: This study provided quantified risk estimates for lung cancer from residential radon exposure among both never-smokers and ever-smokers. Among never-smokers in radon-prone areas, men were at higher risk of lung cancer than women., Competing Interests: Conflict of interest: E.S. Cheng has no conflicts of interest to declare. Conflict of interest: S. Egger has nothing to disclose. Conflict of interest: S. Hughes has nothing to disclose. Conflict of interest: M. Weber reports other support from Cancer Australia and Australian Department of Health, outside the submitted work. Conflict of interest: J. Steinberg has nothing to disclose. Conflict of interest: B. Rahman has nothing to disclose. Conflict of interest: H. Worth has nothing to disclose. Conflict of interest: A. Ruano-Ravina has nothing to disclose. Conflict of interest: P. Rawstorne has nothing to disclose. Conflict of interest: X.Q. Yu has nothing to disclose., (Copyright ©ERS 2021.)

Klippel-Trenaunay syndrome (KTS) is a congenital disorder associated with capillary, venous, lymphatic vascular malformations, and unilateral hypertrophy of the soft tissue and bone. We report a case of a 5-year-old girl with KTS who was followed up until age 17. The asymmetry of her maxillary dentition became remarkable with growth, although no significant left-right difference in either the maxilla or mandible was recognized. Acceptable occlusion was achieved without fixed orthodontic appliances; however, it was necessary to develop treatment plans in accordance with the general symptoms of the disease.

Background: Perioperative red blood cell transfusion (RBCT) remains common after liver resection and carries risk of increased morbidity and worse oncologic outcomes. We sought to assess the factors associated with perioperative RBCT after hepatectomy with a focus on intraoperative hemodynamics., Methods: We performed a retrospective review of our prospective hepatectomy database, supplemented by a review of anesthetic records of all patients undergoing hepatectomy with hemodynamic monitoring (arterial and central venous pressures [CVP]) from 2003-2012. Primary outcome was perioperative RBCT (during and within 30 d after surgery). After descriptive and univariate comparisons, multivariate analysis was conducted to identify factors associated with RBCT., Results: Of 851 hepatectomies, 530 had complete hemodynamic data and 30.2% (161 of 530) received RBCT. Among transfused patients, female gender (P = 0.01), preoperative anemia (P < 0.001), and major liver resection (P = 0.02) were more common. Mean estimated blood loss was 1.1 L higher (2.0 versus 0.9 L; P < 0.001) and operating time was 1.1 h longer (5.8 versus 4.7 h; P < 0.001) in transfused patients. Trends in intraoperative CVP differed significantly based on transfusion status (P = 0.007). Independent factors associated with RBCT included female gender (odds ratio [OR], 2.27; P = 0.01), preoperative anemia (OR, 2.38; P = 0.03), longer operative time (OR, 1.19 per hour; P = 0.03), and higher intraoperative CVP at 1 h during surgery (OR, 1.10 per mm Hg; P = 0.005)., Conclusions: Likelihood of RBCT is independently associated with female gender, preoperative anemia, longer operative time, and higher intraoperative CVP. Focus on management of preoperative anemia, operative efficiency, and low intraoperative CVP is needed to minimize the need for RBCTs., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Red blood cell transfusions (RBCTs) are associated with cancer recurrence following resection of colorectal cancer. Their impact after colorectal liver metastases (CRLM) resection remains debated. We sought to explore the association between perioperative RBCT and oncologic outcomes following resection of CRLM., Methods: We reviewed patients undergoing partial hepatectomy for CRLM from 2003 to 2012 at a single institution. Date of death was abstracted from a validated population-based cancer registry. Primary outcome was overall survival (OS). Secondary outcome was recurrence-free survival (RFS). Survivals were estimated using Kaplan-Meier methods and compared with log-rank test based on transfusion status. Cox regression analysis examined the association of RBCT with OS and RFS, while adjusting for age, preoperative chemotherapy, Clinical Risk Score, and period of treatment (2003-2007 vs. 2008-2012)., Results: Among 483 patients, 27.5 % received RBCT. Ninety-day postoperative mortality was 4.8 %. At median follow-up of 33 (interquartile range 20.1-54.8) months, 5-year OS was inferior in transfused patients (45.9 vs. 61.0 %; p < 0.0001). Five-year RFS was decreased with RBCT (15.5 vs. 31.6 %; p < 0.0001). The difference persisted when considering only 90-day survivors for 5-year OS (53.1 vs. 61.9 %, p = 0.023) and RFS (15.6 vs. 31.6 %; p < 0.0001). After adjustment for prognostic factors, RBCT was independently associated with decreased OS (hazard ratio 2.24; 95 % confidence interval 1.60-3.15) and RFS (hazard ratio 1.71; 95 % confidence interval 1.28-2.28)., Conclusions: Perioperative RBCT is independently associated with decreased OS and RFS following hepatectomy for CRLM. Interventions to minimize and rationalize the use of RBCT for hepatectomy are warranted to mitigate this detrimental effect on long-term outcomes.

Background: After surgical resection of pancreatic adenocarcinoma, most patients will develop recurrence within 2 years. Intense follow-up is often recommended; however, its impact on survival is unknown. Patient and clinician attitudes towards follow-up were qualitatively assessed along with the perceived benefits and challenges., Methods: A semi-structured interview guide was developed. Purposive sampling identified patients who were in active surveillance or had developed recurrence. Clinicians involved in patient care were also interviewed. Interviews were conducted until saturation was reached and themes were derived using standard qualitative methods., Results: A total of 15 patients and seven clinicians were interviewed. Patient themes included a limited understanding of disease prognosis, a desire for reassurance, a desire to know if and when recurrence occurred and minimal difficulties with follow-up. Clinician themes included expectation that patients are aware of the recurrence risk, a desire to provide reassurance, support for intense follow-up and perceived patient challenges in follow-up. Overall, the dominant theme was one of disconnect between patients and clinicians in the understanding of the disease and its prognosis., Discussion: Patients have an intense need for reassurance and obtain this through follow-up appointments with their oncologists. Consequently, they express few difficulties with the process. Clinicians recognize this desire for reassurance. Patients' understanding and expectations contrast starkly with clinicians' perspectives regarding prognosis., (© 2014 International Hepato-Pancreato-Biliary Association.)

Recent attention regarding the impacts of oil and gas development and exploitation has focused on the unintentional release of hydrocarbons into the environment, whilst the potential negative effects of other possible avenues of environmental contamination are less well documented. In the hydrocarbon-rich and ecologically sensitive Mackenzie Delta region (NT, Canada), saline wastes associated with hydrocarbon exploration have typically been disposed of in drilling sumps (i.e., large pits excavated into the permafrost) that were believed to be a permanent containment solution. However, failure of permafrost as a waste containment medium may cause impacts to lakes in this sensitive environment. Here, we examine the effects of degrading drilling sumps on water quality by combining paleolimnological approaches with the analysis of an extensive present-day water chemistry dataset. This dataset includes lakes believed to have been impacted by saline drilling fluids leaching from drilling sumps, lakes with no visible disturbances, and lakes impacted by significant, naturally occurring permafrost thaw in the form of retrogressive thaw slumps. We show that lakes impacted by compromised drilling sumps have significantly elevated lakewater conductivity levels compared to control sites. Chloride levels are particularly elevated in sump-impacted lakes relative to all other lakes included in the survey. Paleolimnological analyses showed that invertebrate assemblages appear to have responded to the leaching of drilling wastes by a discernible increase in a taxon known to be tolerant of elevated conductivity coincident with the timing of sump construction. This suggests construction and abandonment techniques at, or soon after, sump establishment may result in impacts to downstream aquatic ecosystems. With hydrocarbon development in the north predicted to expand in the coming decades, the use of sumps must be examined in light of the threat of accelerated permafrost thaw, and the potential for these industrial wastes to impact sensitive Arctic ecosystems.

Frequency-selective bolometers (FSBs) are a new type of detector for millimeter and submillimeter wavelengths that are transparent to all but a narrow range of frequencies as set by characteristics of the absorber itself. Therefore stacks of FSBs tuned to different frequencies provide a low-loss compact method for utilizing a large fraction of the light collected by a telescope. Tests of prototype FSBs indicate that the absorption spectra are well predicted by models, that peak absolute absorption efficiencies of the order of 50% are attainable, and that their out-of-band transmission is high.

Petrol is one of the most widely used and freely available fuels in use in developed countries today. This study examines the clinical details and demographics of adults with petrol burns over a 10-year period with a view to identifying any trends. The majority of petrol burns were due to human error and thus theoretically preventable. This study determined that the young male (aged 16-25) is most at risk, mainly through the misuse of petrol. The best method of prevention of these burns might be education targeting this group of population. This study provides a basis upon which effective intervention programmes can be designed.

The most massive galaxies and the richest clusters are believed to have emerged from regions with the largest enhancements of mass density relative to the surrounding space. Distant radio galaxies may pinpoint the locations of the ancestors of rich clusters, because they are massive systems associated with 'overdensities' of galaxies that are bright in the Lyman-alpha line of hydrogen. A powerful technique for detecting high-redshift galaxies is to search for the characteristic 'Lyman break' feature in the galaxy colour, at wavelengths just shortwards of Lyalpha, which is due to absorption of radiation from the galaxy by the intervening intergalactic medium. Here we report multicolour imaging of the most distant candidate protocluster, TN J1338-1942 at a redshift z approximately 4.1. We find a large number of objects with the characteristic colours of galaxies at that redshift, and we show that this excess is concentrated around the targeted dominant radio galaxy. Our data therefore indicate that TN J1338-1942 is indeed the most distant cluster progenitor of a rich local cluster, and that galaxy clusters began forming when the Universe was only ten per cent of its present age.

We describe the design, fabrication, measurement, and performance of a set of cryogenic millimetersubmillimeter wavelength filters used in a balloonborne bolometric radiometer. The set contains single resonant mesh grids used as dichroic beam splitters, resonant meshes in a double quarter-wave configuration, a commercial inductive grid filter, and high-frequency blocking filters. The resultant system has passbands at λ = 1.73, 1.05, 0.61, 0.44 mm with δλ/λ = 0.23, 0.23, 0.12, 0.06. Limits on high-frequency leakage are deduced from laboratory measurements and from the analysis of flight data. The filter set response to three different sources of radiation is presented to show the method and limitations of our characterization. The key element of the filter system is a resonant periodic array of cross-shaped holes etched in thin aluminum. We give an empirical scaling law for the resonant wavelength as a function of structure parameters for aluminum on 25-µm-thick Mylar. Plots of the transmittance for normally incident radiation and the transmittance and reflectance for a 45° incident radiation are presented.

The National Aeronautics and Space Administration (NASA) has flown the COBE satellite to observe the Big Bang and the subsequent formation of galaxies and large-scale structure. Data from the Far-Infrared Absolute Spectrophotometer (FIRAS) show that the spectrum of the cosmic microwave background is that of a black body of temperature T = 2.73 +/- 0.06 K, with no deviation from a black-body spectrum greater than 0.25% of the peak brightness. The data from the Differential Microwave Radiometers (DMR) show statistically significant cosmic microwave background anisotropy, consistent with a scale-invariant primordial density fluctuation spectrum. Measurements from the Diffuse Infrared Background Experiment (DIRBE) provide new conservative upper limits to the cosmic infrared background. Extensive modeling of solar system and galactic infrared foregrounds is required for further improvement in the cosmic infrared background limits.

We describe the design, construction, and performance of a resonant cryogenic chopper that operates at 4.2 K. The chopper is mechanically and thermally robust; it can occult a 2.54-cm aperture at 4.5 Hz while dissipating ~1 mW. Both the stator and rotor magnetic fields are controllable to allow for performance optimization and to help in measuring any possible interference effects. Data on long-term amplitude stability are presented.

125I-Labeled rat tonin was injected iv into male Wistar rats weighing 303 +/- 17 g (mean +/- SE), and the disappearance from the circulation, plasma interaction, tissue uptake, and metabolism of radioactivity was studied. After injection, 125I-labeled tonin was immediately bound by alpha 1-macroglobulin, the major circulating protease inhibitor of rats, and the complex was cleared in a biexponential manner: t1/2 of the fast component = 1.8 +2- 0.1 min; t1/2 of the slow component = 84 +/- 10 min; MCR = 2.1 +/- 0.2 ml/min (mean +/- SE, n = 8). The complex was taken up intact by tissues, the major ones being the liver, spleen, adrenal, thyroid, and kidney. Analysis of tissue extracts by gel filtration on Sephadex G-100 showed that the kidney was the major site of metabolism, and radioactivity similar in size to 125I appeared rapidly in urine. Therefore tonin circulates wholly as a complex with alpha 1-macroglobulin (the rat equivalent of human alpha 2-macroglobulin), which once formed is quickly eliminated from the bloodstream by tissue uptake and metabolized.

Tonin is a serine protease found in high concentrations in the submandibular gland (SMG) of the adult rat where it has been localized by immunohistochemistry in the granular ducts. The present study examined the development of tonin in the SMG, the effect of lactation and of stimulation of tonin release, using the peroxidase-antiperoxidase technique and antitonin. Tonin-like immunoreactivity first appeared in the primitive striated duct of the SMG on day 19 foetal and increased in intensity as the ducts developed into granular ducts. Reaction product in granules was seen on day 17 postpartum. Its localization within granules was established by immunochemistry of Sepharose beads to which had been coupled the contents of granules isolated from adult rats. The granular ducts of female rats, which are less developed than in the male, showed a marked increase in tonin-immunoreactivity during lactation. Stimulation of tonin secretion by isoprenaline caused massive discharge of tonin-like immunoreactivity into the lumen of the granular ducts during in vitro incubation. However, within one hour complete regranulation was apparent. The secretion was prevented by propranolol. The results indicate that tonin or a tonin-like substance appears in the rat submandibular gland late in gestation in ducts that presumably develop into granular ducts where it is found in abundance in granules in the adult, that the amount in females is increased during lactation, and that most of the granules are discharged during stimulation, only to be rapidly replaced.