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Lung diseases disproportionately affect elderly individuals. The lungs form a unique environment: a highly elastic organ with gaseous exchange requiring the closest proximity of inhaled air containing harmful agents and the circulating blood. The lungs are highly susceptible to senescence, with age and 'inflammageing' creating a pro-inflammatory environment with a reduced capacity to deal with challenges. While lung diseases may have disparate causes, the burden of ageing and inflammation provides a common process that can exacerbate seemingly unrelated pathologies. However, these shared pathways may also provide a common route to treatment, with increased interest in drugs that target ageing processes across respiratory diseases. In this review, we will examine the evidence for the increased burden of lung disease in older adults, the structural and functional changes seen with advancing age and assess what our expanding knowledge of inflammation and ageing pathways could mean for the treatment of lung disease. LINKED ARTICLES: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc.

Comics Plus offers subscribers a digital library of comics, manga, and graphic novels licensed from more than 100 different publishers, including such indie gems as IDW, Boom Studios, Dark Horse, and Kodansha Comics. Its all-access package includes more than 20,000 titles, about 14,000 of which are appropriate for K-12 readers. Granular title control gives admins the power to customize Comics Plus to suit the readers they serve. But some titles aren't included at all, namely the best-selling books of the industry's top players. Comics Plus may someday persuade these publishers‐‐Marvel, DC, Image, and VIZ Media‐‐to play ball. Until then, most librarians will need to supplement Comics Plus with other methods of acquisition.

Depending on model sizes and test speeds, model Reynolds numbers are typically one to two orders of magnitude less than those occurring at full scale. The region of laminar flow is significantly larger on a model surface than at full scale. Turbulence stimulators (TSs) are extensively applied in model resistance tests to simulate ship boundary layer flow. Because of lack of theoretical guidance, the size, shape, and location of turbulent stimulators used in each test facility are typically selected based on experience gained in each laboratory, and parasitic drag induced by TSs is subtracted from measured model resistance in some test facilities and not subtracted in other facilities. If turbulence stimulation can be specified in such a way as to achieve momentum thickness similarity between the model and full scale, the form factor will be constant, so a simple scaling formula can be applied to predict ship resistance. Ship resistance can be predicted from measured model resistance with the application of this simple scaling formula. The article describes how for a given body geometry, ship Reynolds number and model Reynolds number, a unique TS (size, shape, and location) can be designed based on three equations derived in this article. This uniquely designed TS is termed the "resistance similitude simulator" in this article. The parasitic drag induced by the simulator is a part of the similarity solution and does not need to be subtracted from measured model resistance. 1. Introduction The ability to predict resistance plays an important role in the design of a ship or submarine. An accurate prediction of the drag of the vessel is required for the propulsor design and to determine the required power. The resistance of the vessel also strongly influences its lifetime operation costs. Although computational methods are now commonly used to estimate ship resistance, model tests are still heavily relied on, and scaling formulae are used to relate model data to full-scale performance.

Ceftriaxone-resistant Salmonella enterica serotype Typhi (Typhi), the bacterium that causes typhoid fever, is a growing public health threat. Extensively drug-resistant (XDR) Typhi is resistant to ceftriaxone and other antibiotics used for treatment, including ampicillin, chloramphenicol, ciprofloxacin, and trimethoprim-sulfamethoxazole (1). In March 2018, CDC began enhanced surveillance for ceftriaxone-resistant Typhi in response to an ongoing outbreak of XDR typhoid fever in Pakistan. CDC had previously reported the first five cases of XDR Typhi in the United States among patients who had spent time in Pakistan (2). These illnesses represented the first cases of ceftriaxone-resistant Typhi documented in the United States (3). This report provides an update on U.S. cases of XDR typhoid fever linked to Pakistan and describes a new, unrelated cluster of ceftriaxone-resistant Typhi infections linked to Iraq. Travelers to areas with endemic Typhi should receive typhoid vaccination before traveling and adhere to safe food and water precautions (4). Treatment of patients with typhoid fever should be guided by antimicrobial susceptibility testing whenever possible (5), and clinicians should consider travel history when selecting empiric therapy.

RationalInfection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify therapeutic targets to treat disease.ObjectivesExamine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC).MethodsIsolated neutrophils from 41 non-ICU COVID-19 patients and 23 AMC underwent ex vivo analyses for migration, phagocytosis of Streptococcus pneumoniae, reactive oxygen species (ROS) generation, neutrophil extracellular trap formation (NETosis) and cell surface receptor expression. Serum DNAse 1 activity was measured, alongside circulating levels of cell-free (cf)DNA, myeloperoxidase (MPO), VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3–5 post hospitalisation were also measured.ResultsCompared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (p

Cases of extensively drug-resistant (XDR) typhoid fever have been reported in the United States among patients who did not travel internationally. Clinicians should consider if and where the patient traveled when selecting empiric treatment for typhoid fever. XDR typhoid fever should be treated with a carbapenem, azithromycin, or both.

BACKGROUND Ablative therapies (AT) are widely utilized as bridging treatment for liver transplantation (LT) candidates with hepatocellular carcinoma (HCC) who are on the transplant waiting list to minimize dropout rate. We aimed to investigate whether AT could be considered a primary treatment modality for LT candidates with single, small HCC lesions. MATERIAL AND METHODS We retrospectively investigated the outcomes of patients with AT for single HCC lesions as primary treatment or bridging to LT between 2010 and 2017, compared with surgical resection (SR) during the same time period as control. Univariate and multivariate survival analyses were performed. Matched analysis, after propensity score matching (PSM), was performed to minimize the selection bias confounding effect on outcomes. RESULTS Of 162 patients identified, 92 received AT and 70 had SR. PSM identified 38 paired matches in each group. Overall survival (OS) and disease-free survival (DFS) before matching showed comparable outcomes for each treatment after 1, 3, and 5 years. Multivariate analysis using Cox regression models adjusting the study confounders showed lesion size (>30 mm), not treatment received, was associated with worse DFS (hazard ratio, 2.21 [95% confidence interval, 1.14-4.28]). In the matched groups, OS and DFS were equivalent and consistent with the whole-cohort survival outcomes. Explant histopathology of patients having AT as a bridge to LT showed complete pathological response in 85.7% of patients. CONCLUSIONS This study supports the use of AT with curative intent for single ≤3-cm HCCs, particularly in LT candidates, with salvage transplantation kept as a backup in case of recurrence.

Infection and inflammation of the lung results in the recruitment of non-resident immune cells, including neutrophils, eosinophils and monocytes. This swift response should ensure clearance of the threat and resolution of stimuli which drive inflammation. However, once the threat is subdued this influx of immune cells should be followed by clearance of recruited cells through apoptosis and subsequent efferocytosis, expectoration or retrograde migration back into the circulation. This cycle of cell recruitment, containment of threat and then clearance of immune cells and repair is held in exquisite balance to limit host damage. Advanced age is often associated with detrimental changes to the balance described above. Cellular functions are altered including a reduced ability to traffic accurately towards inflammation, a reduced ability to clear pathogens and sustained inflammation. These changes, seen with age, are heightened in lung disease, and most chronic and acute lung diseases are associated with an exaggerated influx of immune cells, such as neutrophils, to the airways as well as considerable inflammation. Indeed, across many lung diseases, pathogenesis and progression has been associated with the sustained presence of trafficking cells, with examples including chronic diseases such as Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis and acute infections such as Pneumonia and Pneumonitis. In these instances, there is evidence that dysfunctional and sustained recruitment of cells to the airways not only increases host damage but impairs the hosts ability to effectively respond to microbial invasion. Targeting leukocyte migration in these instances, to normalise cellular responses, has therapeutic promise. In this review we discuss the current evidence to support the trafficking cell as an immunotherapeutic target in lung disease, and which potential mechanisms or pathways have shown promise in early drug trials, with a focus on the neutrophil, as the quintessential trafficking immune cell.

RationalInfection with the SARS-CoV2 virus is associated with elevated neutrophil counts. Evidence of neutrophil dysfunction in COVID-19 is based predominantly on transcriptomics or single functional assays. Cell functions are interwoven pathways, and so understanding the effect of COVID-19 across the spectrum of neutrophil function may identify tractable therapeutic targets.ObjectivesExamine neutrophil phenotype and functional capacity in COVID-19 patients versus age-matched controls (AMC)MethodsIsolated neutrophils from 41 hospitalised, non-ICU COVID-19 patients and 23 AMC underwentex vivoanalyses for migration, bacterial phagocytosis, ROS generation, NET formation (NETosis) and cell surface receptor expression. DNAse 1 activity was measured, alongside circulating levels of cfDNA, MPO, VEGF, IL-6 and sTNFRI. All measurements were correlated to clinical outcome. Serial sampling on day 3-5 post hospitalisation were also measured.ResultsCompared to AMC, COVID-19 neutrophils demonstrated elevated transmigration (p=0.0397) and NETosis (p=0.0366), but impaired phagocytosis (p=0.0236) associated with impaired ROS generation (pConclusionCOVID-19 is associated with neutrophil dysfunction across all main effector functions, with altered phenotype, elevated migration, impaired antimicrobial responses and elevated NETosis. These changes represent a clear mechanism for tissue damage and highlight that targeting neutrophil function may help modulate COVID-19 severity.

Introduction: Neutrophils are the most abundant inflammatory cells in the lungs of patients with chronic lung diseases, especially COPD, yet despite this, patients often experience repeated chest i...

The aim of this systematic literature review (SLR) was to investigate the effect of companion animals (whether simply as pets or used in more formal intervention approaches) on the physical and mental health of older adults (aged 60+).. The reviewers identified key search terms and conducted a systematic search of the PsycINFO and PubMed databases. The 70 articles reviewed were evaluated through tabular and thematic analysis.. In 52 of the studies examined, companion animals positively contributed to the mental and/or physical health of older adults. With respect to mental health, involvement with a companion animal improved participant quality of life and effectively attenuated symptoms of depression, anxiety, cognitive impairment, and the behavioral and psychiatric symptoms of dementia (BPSD). In relation to physical health, marked increases in physical activity and improvements in blood pressure and heart rate variability were the only consistent physical health improvements observed from companion animal interactions.. Animal companionship can benefit the mental and physical health of older adults, although more and better controlled research on this topic is required.. Use of companion animals has the potential to be an effective treatment or adjunct therapy to improve the health status and quality of life of older individuals.

BACKGROUND The COVID-19 pandemic has led to many countries implementing lockdown procedures, resulting in the suspension of laboratory research. With lockdown measures now easing in some areas, many laboratories are preparing to reopen. This is particularly challenging for clinical research laboratories due to the dual risk of patient samples carrying the virus that causes COVID-19, SARS-CoV-2, and the risk to patients being exposed to research staff during clinical sampling. To date, no confirmed transmission of the virus has been confirmed within a laboratory setting; however, operating processes and procedures should be adapted to ensure safe working of samples of positive, negative, or unknown COVID-19 status. OBJECTIVE In this paper, we propose a framework for reopening a clinical research laboratory and resuming operations with the aim to maximize research capacity while minimizing the risk to research participants and staff. METHODS This framework was developed by consensus among experienced laboratory staff who have prepared to reopen a clinical research laboratory. RESULTS Multiple aspects need to be considered to reopen a clinical laboratory. We describe our process to stratify projects by risk, including assessment of donor risk and COVID-19 clinical status, the COVID-19 status of the specific sample type, and how to safely process each sample type. We describe methods to prepare the laboratory for safe working including maintaining social distancing through signage, one-way systems and access arrangements for staff and patients, limiting staff numbers on site and encouraging home working for all nonlaboratory tasks including data analysis and writing. Shared equipment usage was made safe by adapting booking systems to allow for the deployment of cleaning protocols. All risk assessments and standard operating procedures were rewritten and approved by local committees, and staff training was initiated to ensure compliance. CONCLUSIONS Laboratories can adopt and adapt this framework to expedite reopening a clinical laboratory during the current COVID-19 pandemic while mitigating the risk to research participants and staff.

We present the case of a patient who developed myalgia as the primary symptom of envenomation by the eastern coral snake, Micrurus fulvius. The patient was evaluated and treated in the emergency department. Physical examination did not demonstrate any neuromuscular abnormalities. On consultation with the poison control center, the patient's myalgia was determined to be an effect of envenomation, and 5 vials of North American coral snake antivenin were administered. The patient was admitted to the intensive care unit where his symptoms resolved. He was discharged the following day after remaining asymptomatic for 24 h.

The risk of poor post-operative outcome and the benefits of surgical resection as a curative therapy require careful assessment by the clinical care team for patients with primary and secondary liver cancer. Advances in surgical techniques have improved patient outcomes but identifying which individual patients are at greatest risk of poor post-operative liver performance remains a challenge. Here we report results from a multicentre observational clinical trial (ClinicalTrials.gov NCT03213314) which aimed to inform personalised pre-operative risk assessment in liver cancer surgery by evaluating liver health using quantitative multiparametric magnetic resonance imaging (MRI). We combined estimation of future liver remnant (FLR) volume with corrected T1 (cT1) of the liver parenchyma as a representation of liver health in 143 patients prior to treatment. Patients with an elevated preoperative liver cT1, indicative of fibroinflammation, had a longer post-operative hospital stay compared to those with a cT1 within the normal range (6.5 vs 5 days; p = 0.0053). A composite score combining FLR and cT1 predicted poor liver performance in the 5 days immediately following surgery (AUROC = 0.78). Furthermore, this composite score correlated with the regenerative performance of the liver in the 3 months following resection. This study highlights the utility of quantitative MRI for identifying patients at increased risk of poor post-operative liver performance and a longer stay in hospital. This approach has the potential to inform the assessment of individualised patient risk as part of the clinical decision-making process for liver cancer surgery.

BACKGROUND: Laparoscopic liver resection (LLR) is increasingly common worldwide but its suitability in patients with cirrhosis is not clearly defined. There are minimal data in the western literature on this topic and previous work has compared LLR to open hepatectomy rather than to LLR in non-cirrhotic patients. This study compared short-term outcomes of LLR in cirrhotic patients to LLR in non-cirrhotic patients. METHODS: Retrospective review of minor LLR at the Royal Infirmary of Edinburgh from January 2006 to January 2018 was conducted. Patients were stratified by whether they had cirrhosis - defined as per radiological appearances and liver function tests. Variables of interest included baseline clinicopathological information with short-term outcomes (length of stay and complications) regarded as the primary outcome of interest. RESULTS: Out of 1207 liver resections in the study period, there were 120 LLR with 30 patients having cirrhosis. Patients with cirrhosis were more likely to be male and have higher median American Society of Anesthesiologists scores (3 versus 2; P

In February 2018, a typhoid fever outbreak caused by Salmonella enterica serotype Typhi (Typhi), resistant to chloramphenicol, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and third-generation cephalosporins, was reported in Pakistan. During November 2016-September 2017, 339 cases of this extensively drug-resistant (XDR) Typhi strain were reported in Pakistan, mostly in Karachi and Hyderabad; one travel-associated case was also reported from the United Kingdom (1). More cases have been detected in Karachi and Hyderabad as surveillance efforts have been strengthened, with recent reports increasing the number of cases to 5,372 (2). In the United States, in response to the reports from Pakistan, enhanced surveillance identified 29 patients with typhoid fever who had traveled to or from Pakistan during 2016-2018, including five with XDR Typhi. Travelers to areas with endemic disease, such as South Asia, should be vaccinated against typhoid fever before traveling and follow safe food and water practices. Clinicians should be aware that most typhoid fever infections in the United States are fluoroquinolone nonsusceptible and that the XDR Typhi outbreak strain associated with travel to Pakistan is only susceptible to azithromycin and carbapenems.

Silybum marianum (L.) Gaertner (Milk thistle) extracts have been widely used for the treatment of liver pathologies and as a hepatoprotectant against alcohol-induced liver diseases and other harmful drug metabolites or toxins. Silymarin, the active fraction of Silybum marianum tinctures, accounts for 70–80% of the plant's hydro-alcoholic extract and consists of a mixture of flavonolignans and a flavonoid. Silybum marianum tinctures are commonly prescribed by herbal practitioners for the treatment of liver diseases. However, previous studies have showed inconsistency in the therapeutic efficacy of Silybum marianum tinctures, which is believed to have arisen from the content variability of silymarin, resulting from lack of standardized and regulated manufacturing processes. This work was conducted to quantify the silymarin content in commercial Silybum marianum tinctures in order to evaluate their quality. In this study, we report the determination of the total silymarin content in eleven different commercial tinctures retailed in the U.K. using a convenient and accurate HPLC-UV method. The tinctures analyzed differed in the ratio between herb and liquid as well as percentage of ethanol used during the extraction process. Our results showed a direct correlation between the silymarin content in tinctures and the alcohol strength. Following our protocol, silymarin could not be detected in tinctures extracted with 25% ethanol. Effective therapeutic doses were found only in tinctures with a concentration ratio herb to liquid 1:1 (kg/L) and an alcoholic content of 70%. To guarantee quality and safety of herbal medicinal products, legal requirements to produce plant-based products under regulatory frameworks are needed.

Key Points Question Are pet store puppies a source of extensively drug-resistant Campylobacter jejuni infection in the US? Findings This survey study identified 168 cases from public health reports of Campylobacter infections with an epidemiologic or molecular link to pet store puppies from 2011 to 2020; 97% of patients reported contact with a dog, of whom 88% reported contact with a pet store puppy. Isolates were resistant to 7 antibiotic classes, including all recommended treatment agents. Meaning Extensively drug-resistant C jejuni strains have emerged as a cause of illness among pet store customers, employees, and visitors; infections caused by these strains cannot be treated with commonly recommended oral antibiotics., Importance Extensively drug-resistant Campylobacter jejuni infections cannot be treated with any commonly recommended antibiotics and pose an increasing public health threat. Objectives To investigate cases of extensively drug-resistant C jejuni associated with pet store puppies and describe the epidemiologic and laboratory characteristics of these infections. Design, Setting, and Participants In August 2017, health officials identified, via survey, patients with C jejuni infections who reported contact with puppies sold by pet stores. In conjunction with state and federal partners, the Centers for Disease Control and Prevention investigated cases of culture-confirmed C jejuni infections in US patients with an epidemiologic or molecular association with pet store puppies between January 1, 2016, and February 29, 2020. Available records from cases occurring before 2016 with genetically related isolates were also obtained. Main Outcomes and Measures Patients were interviewed about demographic characteristics, health outcomes, and dog exposure during the 7 days before illness onset. Core genome multilocus sequence typing was used to assess isolate relatedness, and genomes were screened for resistance determinants to predict antibiotic resistance. Isolates resistant to fluoroquinolones, macrolides, and 3 or more additional antibiotic classes were considered to be extensively drug resistant. Cases before 2016 were identified by screening all sequenced isolates submitted for surveillance using core genome multilocus sequence typing. Results A total of 168 patients (median [interquartile range] age, 37 [19.5-51.0] years; 105 of 163 female [64%]) with an epidemiologic or molecular association with pet store puppies were studied. A total of 137 cases occurred from January 1, 2016, to February 29, 2020, with 31 additional cases dating back to 2011. Overall, 117 of 121 patients (97%) reported contact with a dog in the week before symptom onset, of whom 69 of 78 (88%) with additional information reported contact with a pet store puppy; 168 isolates (88%) were extensively drug resistant. Traceback investigation did not implicate any particular breeder, transporter, distributer, store, or chain. Conclusions and Relevance Strains of extensively drug-resistant C jejuni have been circulating since at least 2011 and are associated with illness among pet store customers, employees, and others who come into contact with pet store puppies. The results of this study suggest that practitioners should ask about puppy exposure when treating patients with Campylobacter infection, especially when they do not improve with routine antibiotics, and that the commercial dog industry should take action to help prevent the spread of extensively drug-resistant C jejuni from pet store puppies to people., This survey study investigates the epidemiologic, laboratory, and traceback findings associated with persistent, extensively drug-resistant strains of Campylobacter jejuni associated with US pet store puppies.

In memory of Ronald Coleman of Chapel Hill, Queensland, Australia (1938–2008)SUMMARY: The Tuscan origin of the characteristic large oil jars found all over the world was confirmed by neutron activation analysis about 20 years ago, although some still call them Iberian storage jars. Our paper presents the unpublished analytical data and considers whose oil they contained. Italian records show that in the 18th century Montelupo despatched coppi (jars) down the River Arno to Lucca, where the best Italian olive oil was produced, and to Livorno (Leghorn), then the largest emporium in the Mediterranean for transit trade. In London, the jars became a familiar sight with different high and popular cultural meanings.

Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

INTRODUCTION: Prehabilitation prior to major surgery has increased in popularity over recent years and aims to improve pre-operative conditioning of patients to improve post-operative outcomes. The beneficial effect of such protocols is not well established with conflicting results reported. This review aimed to assess the effect of prehabilitation on post-operative outcome after major abdominal surgery.METHODS: EMBASE, Medline, PubMed and the Cochrane database were searched in August 2018 for trials comparing outcomes of patients undergoing prehabilitation involving prescribed respiratory and exercise interventions prior to abdominal surgery. Study characteristics, overall and pulmonary morbidity, length of stay (LOS), maximum inspiratory pressure and change in six-minute walking test (6MWT) distance were obtained. The primary outcome was post-operative overall morbidity within 30 days. Dichotomous data were analysed by fixed or random effects odds ratio. Continuous data were analysed with weighted mean difference.RESULTS: Fifteen RCTs were included in the analysis with 457 prehabilitation patients and 450 control group patients. A significant reduction in overall (OR 0.63 95% CI 0.46-0.87 I2 34%, p = 0.005) and pulmonary morbidity (OR 0.4 95% CI 0.23-0.68, I2 = 0%, p = 0.0007) was observed in the prehabilitation group. No significant difference in LOS (WMD -2.39 95% CI -4.86 to 0.08 I2 = 0%, p = 0.06) or change in 6MWT distance (WMD 9.06 95% CI -35.68, 53.81 I2 = 88%, p = 0.69) was observed.CONCLUSIONS: Prehabilitation can reduce overall and pulmonary morbidity following surgery and could be utilised routinely. The precise protocol of prehabilitation has not been completely established. Further work is required to tailor optimal prehabilitation protocols for specific operative procedures.

The US Navy is developing a new computationally efficient simulation tool to predict the responses of a ship operating in severe sea states. The tool computes the total force on the ship as the summation of component forces. An important component to the total force on the ship is the force from hull lift and cross-flow separation. These forces are predicted in calm water by maneuvering simulation tools but are often ignored by traditional seakeeping simulation tools. As viscous effects are important in the prediction of these forces, most maneuvering simulations are based on empirical data from calm water maneuvering tests. While these methods are valid in calm water the wetted shape of the hull changes significantly in large waves having significant influences on the hull lift and cross flow drag forces. In the present method a hull lift and cross flow drag force model is presented that accounts for the varying wetted geometry of the hull in waves. The method uses calm water maneuvering data from model tests and RANS calculations to calibrate the model. Proper modeling of the hull lift and cross flow drag force in large waves is very important for the prediction of some dynamic stability events such as broaching and broaching leading to capsize.

A new appendage resistance prediction method, which mitigates the technical issues with the existing test procedure, has been developed and presented in this paper. The primary aspects of the new method are 1) the Froude's equivalent flat plate friction drag concept extensively used in the marine industry will not be used in the present method, instead, an aerodynamic profile drag concept for resistance prediction is presented, 2) the turbulent stimulators extensively used in existing model appendage resistance tests will not be used in the proposed test procedure, which eliminates the need for high-speed tests and the problematic issue of estimating the parasitic drag associated with turbulence stimulators, 3) the important juncture vortex drag associated with appendages is considered, 4) the effective velocity entering the stern appendages on resistance is considered, 5) the new scaling formula to relate model profile drag and juncture vortex drag to full-scale appendage drag is developed and presented in this paper.

Enhanced Recovery After Surgery protocols have been implemented effectively after liver resection and provide benefits in terms of general morbidity rates. In order to optimise peri-operative care protocols and minimise morbidity, further investigation is required to identify factors associated with poor outcome after liver resection.A retrospective analysis of patients undergoing liver resection and enhanced recovery care between January 2006 and September 2012 was conducted. Data were collected on patient outcome and demographics, operative and pathological details. Univariate and multivariate analyses were performed to determine independent predictors of adverse outcome.603 patients underwent liver resection during the study period. Morbidity and mortality rates were 34.3% and 1.5% respectively. The only predictor of major morbidity was extended resection (OR 4.079; 95% CI 2.177-7.642).Extended resection is associated with major morbidity. When determining optimum peri-operative care, ERAS protocols must incorporate care components that can mitigate against morbidity associated with extended resection.

Background The effect of liver resection on acetaminophen metabolism and whether it is affected by residual liver volume is poorly understood. Methods We investigated the effects of liver resection on acetaminophen metabolism in a single centre, prospective observational, case–control study of inpatients. Patients undergoing liver resection were administered therapeutic post-operative acetaminophen. Glutathione and urinary acetaminophen metabolites were measured over the first three post-operative days and compared between patients with low (Group A) and high (Group B) residual liver volume. Results 41 patients (41% female, median age 62 [IQR 53–72] years) were included. Mean urinary cysteine levels increased significantly from post-operative day 1 to 2 (578.0 mg/day 95% CI 478.9–677.1 vs. 775.4 mg/day, 95% CI 625.7–925.1; p = 0.03). Group A ( n = 11) had significantly higher median levels of cysteine (day 1, 464.3 mg/day [IQR 355.6–582.0]; day 3, 717.6 mg/day [IQR 423.5–1104.0]) compared to Group B ( n = 11): day 1, 545.4 mg/day (IQR 346.9–843.5); day 3, 508.1 mg/day (IQR 390.8–788.4; p = 0.048). No significant difference was observed in glutathione or 5-oxoproline levels between the groups. Conclusion Low residual liver volume results in altered acetaminophen metabolism, however, no evidence of glutathione deficiency was observed. Therapeutic acetaminophen is safe after major liver resection provided liver function is adequate.

Background A liver resection under low central venous pressure (CVP) has become standard practice; however, the benefits beyond a reduction in blood loss are not well reported. Moreover, the precise method to achieve CVP reduction has not been established. A systematic review and meta analysis of randomized controlled trials (RTCs) was performed to assess the effects of CVP on clinical outcome and to identify the optimum method of CVP reduction. Methods EMBASE, Medline, PubMed and the Cochrane database were searched for trials comparing low CVP surgery with controls. The primary outcome was post operative complications within 30 days. Secondary outcomes included estimated blood loss (EBL), blood transfusion rates and length of stay (LOS). Sub group analysis was performed to assess the CVP reduction method on the outcome. Results Eight trials were identified. No difference was observed in the morbidity rate between the high CVP and control groups [odds ratio (OR) = 0.96 (95% confidence interval (CI) 0.66, 1.40) P = 0.84, I 2 = 0%]. EBL [weighted mean difference (WMD) = −308.63 ml (95% CI −474.67, −142.58) P = I 2 = 73%] and blood transfusion rates [OR 0.65 (95% CI 0.44, 0.97) P = 0.040, I 2 = 37%] were significantly lower in the low CVP groups. Neither anaesthetic nor surgical methods of CVP reduction were associated with a reduced post operative morbidity. Conclusion Low CVP surgery is associated with a reduction in EBL; however, this does not translate into an improvement in post operative morbidity. The optimum method of CVP reduction has not been identified.