Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis.

Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA. MATERIALS AND METHODS: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). RESULTS: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43-0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12-0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. CONCLUSION: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.

Cost-effectiveness of gallbladder histopathology after cholecystectomy for benign disease.

BACKGROUND: The prevalence of incidental gallbladder cancer is low when performing cholecystectomy for benign disease. The performance of routine or selective histological examination of the gallbladder is still a subject for discussion. The aim of this study was to assess the cost-effectiveness of these different approaches. METHODS: Four management strategies were evaluated using decision-analytical modelling: no histology, current selective histology as practised in Sweden, macroscopic selective histology, and routine histology. Healthcare costs and life-years were estimated for a lifetime perspective and combined into incremental cost-effectiveness ratios (ICERs) to assess the additional cost of achieving an additional life-year for each management strategy. RESULTS: In the analysis of the four strategies, current selective histology was ruled out due to a higher ICER compared with macroscopic selective histology, which showed better health outcomes (extended dominance). Comparison of routine histology with macroscopic selective histology resulted in a gain of 12 life-years and an incremental healthcare cost of approximately €1 000 000 in a cohort of 10 000 patients, yielding an estimated ICER of €76 508. When comparing a macroscopic selective strategy with no histological assessment, 50 life-years would be saved and the ICER was estimated to be €20 708 in a cohort of 10 000 patients undergoing cholecystectomy. CONCLUSION: A macroscopic selective strategy appears to be the most cost-effective approach.

Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv.

BACKGROUND: Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database. METHODS: Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan-Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment. RESULTS: A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3-6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8-2·9), 0·5 (0·3-1·2) and 0·3 (0·1-1·0) years for the TACE, sorafenib and BSC groups respectively (P < 0·001). Median survival was 0·9 years for the total HCC cohort in 2009-2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013-2016 (P < 0·001). CONCLUSION: The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.

ANTECEDENTES: Se carece datos consistentes acerca de las características clínicas, modalidades terapéuticas y supervivencia a largo plazo en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) basados en registros de calidad de ámbito nacional. El objetivo de este estudio fue describir los patrones de tratamiento y los resultados de supervivencia en pacientes diagnosticados de HCC usando una base de datos nacional. MÉTODOS: Se revisaron las características de los pacientes y los patrones de tratamiento en pacientes con un diagnóstico de HCC incluidos en el registro nacional de tumores de hígado y vías biliares (SweLiv) entre 2009 y 2016. La supervivencia global (overall sirvival, OS) se analizó mediante el método de Kaplan-Meier y test de log-rank para la comparación de subgrupos según las características clínicas de los pacientes, las modalidades de tratamiento y los resultados en función del año de tratamiento. RESULTADOS: Durante un periodo de 7 años, se incluyeron en el registro un total de 3.076 pacientes con HCC, 246 de los cuales recibieron un trasplante (7,2%). Se practicó resección y ablación como tratamiento primerio en 501 (14,8%) y 390 (11,6%) pacientes, respectivamente. La quimioembolización (TACE) y el tratamiento sistémico con sorafenib se efectuó en 476 (14,1%) y 426 (12,6%) pacientes, respectivamente; los 1.337 pacientes restantes (40,0%) fueron incluidos en la base de datos pero se derivaron para recibir el mejor tratamiento de soporte. La tasa de supervivencia a los 5 años fue del 75% en el grupo trasplantado. La mediana de OS fue de 4,6 años (rango intercuartílico, interquartile range, IQR 2,0-no alcanzado) tras la resección y de 3,1 años (IQR 2,3-6,7) tras la ablación. En los pacientes derivados para tratamiento paliativo, la mediana de supervivencia fue de 1,4 años (IQR 0,8-2,9), 0,5 años (IQR 0,2-1,2) y 0,3 años (IQR 0,1-1,0) para los grupos de TACE, sorafenib y mejor tratamiento de soporte, respectivamente (P < 0,001). La mediana de supervivencia para toda la cohorte de HCC en 2009-2012 fue de 0,9 años antes de la publicación del programa de nacional de tratamiento sueco, aumentando a 1,4 años en 2013-2016 (P <0,001). CONCLUSIÓN: Los resultados de supervivencia referidos eran consistentes con resultados previos obtenidos en cohortes más pequeñas; la introducción de guías nacionales puede haber contribuido a mejorar la supervivencia de los pacientes con HCC en Suecia.

Evaluation of health and quality of life in apheresis patients - data from the WAA register.

OBJECTIVE: The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. MATERIAL AND METHODS: Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. RESULTS: Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. CONCLUSION: Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Association between breastfeeding and better preserved cognitive ability in an elderly cohort of Finnish men.

BACKGROUND: Being breastfed in infancy has been shown to benefit neurodevelopment. However, whether the benefits persist to old age remains unclear. METHODS: We examined the associations between breastfeeding and its duration on cognitive ability in young adulthood and old age, and on aging-related cognitive change over five decades. In total, 931 men from the Helsinki Birth Cohort Study born in 1934-1944 in Finland took the Finnish Defence Forces Basic Intellectual Ability Test (total and verbal, arithmetic and visuospatial subtest scores) twice, at ages 20.2 and 67.9 years, and had data on breastfeeding (yes v. no) and its duration ('never breastfed', 'up to 3', '3 to 6' and '6 or more months'). Linear and mixed model regressions tested the associations. RESULTS: At 20.2 years, breastfed men had higher cognitive ability total and visuospatial subtest scores [mean differences (MDs) ranged between 3.0-3.9, p values < 0.013], and its longer duration predicted higher cognitive ability total and arithmetic and visuospatial subtest scores (MDs ranged between 3.0 and 4.8, p values < 0.039). At 67.9 years, breastfed men had higher total cognitive ability and all subtest scores (MDs ranged between 2.6 and 3.4, p values < 0.044) and its longer duration predicted all cognitive ability scores (MDs ranged between 3.1 and 4.7, p values < 0.050). Verbal subtest scores decreased over five decades in men who were never breastfed or were breastfed for 3 months or less, and increased in those breastfed for longer than 3 months. CONCLUSIONS: Neurodevelopmental advantages of breastfeeding and its longer duration persist into old age, and longer duration of breastfeeding may benefit aging-related change, particularly in verbal reasoning ability.

Cardiovascular fitness in late adolescent males and later risk of serious non-affective mental disorders: a prospective, population-based study.

BACKGROUND: Cardiovascular fitness in late adolescence is associated with future risk of depression. Relationships with other mental disorders need elucidation. This study investigated whether fitness in late adolescence is associated with future risk of serious non-affective mental disorders. Further, we examined how having an affected brother might impact the relationship. METHOD: Prospective, population-based cohort study of 1 109 786 Swedish male conscripts with no history of mental illness, who underwent conscription examinations at age 18 between 1968 and 2005. Cardiovascular fitness was objectively measured at conscription using a bicycle ergometer test. During the follow-up (3-42 years), incident cases of serious non-affective mental disorders (schizophrenia and schizophrenia-like disorders, other psychotic disorders and neurotic, stress-related and somatoform disorders) were identified through the Swedish National Hospital Discharge Register. Cox proportional hazards models were used to assess the influence of cardiovascular fitness at conscription and risk of serious non-affective mental disorders later in life. RESULTS: Low fitness was associated with increased risk for schizophrenia and schizophrenia-like disorders [hazard ratio (HR) 1.44, 95% confidence interval (CI) 1.29-1.61], other psychotic disorders (HR 1.41, 95% CI 1.27-1.56), and neurotic or stress-related and somatoform disorders (HR 1.45, 95% CI 1.37-1.54). Relationships persisted in models that included illness in brothers. CONCLUSIONS: Lower fitness in late adolescent males is associated with increased risk of serious non-affective mental disorders in adulthood.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Validation and development of MTH1 inhibitors for treatment of cancer.

BACKGROUND: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. MATERIAL AND METHODS: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. RESULTS: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. CONCLUSION: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.

Total and cause-specific mortality of Finnish military personnel following service in international peacekeeping operations 1990-2010: a comprehensive register-based cohort study.

OBJECTIVES: To estimate total and cause-specific mortality after international peacekeeping deployments among the Finnish military peacekeeping personnel in comparison to the general population of similar age and sex. DESIGN: A register-based study of a cohort of military peacekeeping personnel in 1990-2010 followed for mortality until the end of 2013. Causes of death were obtained from the national Causes of Death Register. The standardised mortality ratio (SMR) for total and cause-specific mortality was calculated as the ratio of observed and expected number of deaths. SETTING: Finland (peacekeeping operations in different countries in Africa, Asia and in an area of former Yugoslavia in Europe). PARTICIPANTS: 14 584 men and 418 women who had participated in international military peacekeeping operations ending between 1990 and 2010. INTERVENTIONS: Participation in military peacekeeping operations. MAIN OUTCOME: Total and cause-specific mortality. RESULTS: 209 men and 3 women died after their peacekeeping service. The SMR for all-cause mortality was 0.55 (95% CI 0.48 to 0.62). For the male peacekeeping personnel, the SMR for all diseases was 0.44 (95% CI 0.35 to 0.53) and for accidental and violent deaths 0.69 (95% CI 0.57 to 0.82). The SMR for suicides was 0.71 (95% CI 0.53 to 0.92). CONCLUSIONS: Even though military peacekeeping personnel are working in unique and often stressful conditions, their mortality after their service is lower compared with the general population. Military peacekeeping personnel appear to be a selected population group with low general mortality and no excess risk of any cause of death after peacekeeping service.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Evaluating equality in psoriasis healthcare: a cohort study of the impact of age on prescription of biologics.

BACKGROUND: Inequality in healthcare has been identified in many contexts. To the best of our knowledge, this is the first study investigating age inequality in the form of prescription patterns of biologics in psoriasis care. OBJECTIVES: To determine whether patients with psoriasis have equal opportunities to receive biological medications as they age. If patients did not receive equal treatment, a subsequent objective was to determine the magnitude of the disparity. METHODS: A cohort of biologic-naive patients with psoriasis was analysed using Cox proportional hazards models to measure the impact of each additional year of life on the likelihood of initiating biological treatment, after controlling for sex, body mass index, comorbidities, disease activity and educational level. A supporting analysis used a nonparametric graphical method to study the proportion of patients initiating biological treatment as age increased, after controlling for the same covariates. RESULTS: The Cox proportional hazards model resulted in hazard ratios of a 1-year increase in age of 0·96-0·97 depending on calendar-year stratification, which implies that an increase in age of 30 years corresponds to a reduced likelihood of initiating biological treatment by 61·3-67·6%. The estimated proportion of patients initiating biological medication always decreased as age increased, at a statistically significant level. CONCLUSIONS: Patients with psoriasis have fewer opportunities to access biological medications as they age. This result was shown to be applicable at all stages in a patient's life course and was not only restricted to the elderly, although it implies greater disparities as the age difference between patients increases. These results show that inequality in access to biological treatments due to age is prevalent in clinical practice today. Further research is needed to investigate the extent to which this result is influenced by patient preferences.

Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy.

OBJECTIVE: To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. METHODS: A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. RESULTS: Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of €467, €551, €739 and €574, respectively. The cost per QALY gained with ticagrelor was €2747, €3395, €4419 and €4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. CONCLUSIONS: Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel. TRIAL REGISTRATION NUMBER: NCT000391872.

X-ray phase contrast with injected gas for tumor microangiography.

We show that the microvasculature of mouse tumors can be visualized using propagation-based phase-contrast x-ray imaging with gas as the contrast agent. The large density difference over the gas-tissue interface provides high contrast, allowing the imaging of small-diameter blood vessels with relatively short exposure times and low dose using a compact liquid-metal-jet x-ray source. The method investigated is applied to tumors (E1A/Ras-transformed mouse embryonic fibroblasts) grown in mouse ears, demonstrating sub-15-µm-diameter imaging of their blood vessels. The exposure time for a 2D projection image is a few seconds and a full tomographic 3D map takes some minutes. The method relies on the strength of the vasculature to withstand the gas pressure. Given that tumor vessels are known to be more fragile than normal vessels, we investigate the tolerance of the vasculature of 12 tumors to gas injection and find that a majority withstand 200 mbar pressures, enough to fill 12-µm-diameter vessels with gas. A comparison of the elasticity of tumorous and non-tumorous vessels supports the assumption of tumor vessels being more fragile. Finally, we conclude that the method has the potential to be extended to the imaging of 15 µm vessels in thick tissue, including mouse imaging, making it of interest for, e.g., angiogenesis research.

Carbon footprint and land requirement for dairy herd rations: impacts of feed production practices and regional climate variations.

Feed production is a significant source of greenhouse gas (GHG) emissions from dairy production and demands large arable and pasture acreage. This study analysed how regional conditions influence GHG emissions of dairy feed rations in a life cycle perspective, that is the carbon footprint (CF) and the land area required. Factors assessed included regional climate variations, grass/clover silage nutrient quality, feedstuff availability, crop yield and feed losses. Using the Nordic feed evaluation model NorFor, rations were optimised for different phases of lactation, dry and growing periods for older cows, first calvers and heifers by regional feed advisors and combined to annual herd rations. Feed production data at farm level were based on national statistics and studies. CF estimates followed standards for life cycle assessment and used emissions factors provided by IPCC. The functional unit was 'feed consumption to produce 1 kg energy corrected milk (ECM) from a cow with annual milk yield of 9 900 kg ECM including replacement animals and feed losses'. Feed ration CF varied from 417 to 531 g CO2 e/kg ECM. Grass/clover silage contributed more than 50% of total GHG emissions. Use of higher quality silage increased ration CF by up to 5% as a result of an additional cut and increased rates of synthetic N-fertiliser. Domestically produced horse bean (Vicia faba), by-products from the sugar industry and maize silage were included in the rations with the lowest CF, but horse bean significantly increased ration land requirement. Rations required between 1.4 to 2 m2 cropland and 0.1 to 0.2 m2/kg semi-natural grassland per kg ECM and year. Higher yield levels reduced ration total CF. Inclusion of GHG emissions from land use change associated with Brazilian soya feed significantly increased ration CF. Ration CF and land use depended on ration composition, which was highly influenced by the regional availability and production of feedstuffs. The impact of individual feedstuffs on ration CF varies due to, for example, cultivation practices and climate conditions and feedstuffs should therefore be assessed in a ration and regional perspective before being used to decrease milk CF. Land use efficiency should be considered together with ration CF, as these can generate goal conflicts.

Hypermobility among school children aged five to eight years: the Hospital del Mar Criteria gives higher prevalence for hypermobility than the Beighton score.

OBJECTIVES: The purpose was to investigate the distribution of hypermobility among school children aged five to eight years. METHODS: One hundred and twenty-eight participants were assessed using the Beighton score and the Hospital del Mar criteria. RESULTS: With the Beighton score using the cut-off ≥4, the prevalence was 12%, and with the Hospital del Mar criteria the prevalence was 34%. There were significantly higher scores for females on both the Beighton (p=0.01) and Hospital del Mar criteria (p<0.0001). The youngest children aged five to six years scored higher compared with the seven- and eight-year-olds (p=0.016). The knee flexion was most likely to be hypermobile (97%), followed by shoulder rotation (80%), thumb (31%), elbow (27%), metatarsal-phalangeal (16%), hip (15.5%), fingers (10%) or knee (10%), ankle (6%), trunk (4%) and patella (2%). CONCLUSIONS: Gender and probably age must be taken into account when children are assessed for hypermobility. The Hospital del Mar criteria need to be modified for some of the motions.

An LCA researcher's wish list--data and emission models needed to improve LCA studies of animal production.

The last decade has seen an increase in environmental systems analysis of livestock production, resulting in a significant number of studies with a holistic approach often based on life-cycle assessment (LCA) methodology. The growing public interest in global warming has added to this development; guidelines for carbon footprint (CF) accounting have been developed, including for greenhouse gas (GHG) accounting of animal products. Here we give an overview of methods for estimating GHG emissions, with emphasis on nitrous oxide, methane and carbon from land use change, presently used in LCA/CF studies of animal products. We discuss where methods and data availability for GHGs and nitrogen (N) compounds most urgently need to be improved in order to produce more accurate environmental assessments of livestock production. We conclude that the top priority is to improve models for N fluxes and emissions from soils and to implement soil carbon change models in LCA/CF studies of animal products. We also point at the need for more farm data and studies measuring emissions from soils, manure and livestock in developing countries.

Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study.

OBJECTIVE: Long-term health sequelae of childhood-onset acute lymphoblastic leukemia (ALL) remain largely unknown. Low bone mineral content (BMC) and bone mineral density (BMD) are recognized complications, but it is unknown whether these persist until adulthood. We evaluated skeletal characteristics and their association with ALL therapy in long-term male ALL survivors. DESIGN: This cross-sectional cohort study included 49 long-term male ALL survivors and 55 age-matched healthy males. METHODS: BMD and compression fractures were assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for parameters of calcium homeostasis. RESULTS: The ALL survivors (median age 29 years, range 25-38 years), assessed 10-38 years after ALL diagnosis, had lower lumbar spine (P<0.001), femoral neck (P<0.001), and whole-body (P=0.017) BMD than expected based on normative values. When compared with the controls (median age 30 years, range 24-36 years), the ALL survivors had lower lumbar spine BMC (P=0.014), lower whole-body BMC (P<0.001), and lower whole-body BMD (P<0.001), but the differences were partly explained by differences in height. Altogether, 20% of the ALL survivors had spinal compression fractures, but these were equally prevalent in the controls. Males diagnosed with ALL before age 5 years had significantly lower BMD values. Other recognized risk factors included untreated hypogonadism, vitamin D deficiency, hypophosphatemia, low IGF-binding protein-3, and low physical activity. CONCLUSIONS: At young adulthood, long-term male ALL survivors have significantly reduced BMC and BMD and a high prevalence of spinal compression fractures. Careful follow-up and active treatment of the recognized risk factors are warranted.

Functional and muscle morphometric effects of ACL reconstruction. A prospective CT study with 1 year follow-up.

Computed tomography (CT) was used to explore if changes in muscle cross-sectional area and quality after anterior cruciate ligament (ACL) injury and reconstruction would be related to knee function. Fourteen females and 23 males (16-54 years) underwent clinical tests, subjective questionnaires, and CT 1 week before and 1 year after ACL surgery with semitendinosus-gracilis (STG) graft and rehabilitation. Postoperatively, knee laxity was decreased and functional knee measures and subjective patient scores improved. The most obvious remaining deficit was the quadriceps atrophy, which was significantly larger if the right leg was injured. Right-leg injury also tended to cause larger compensatory hypertrophy of the combined knee flexor and tibial internal rotator muscles (preoperatively). The quadriceps atrophy was significantly correlated with the scores and functional tests, the latter also being related to the remaining size of the gracilis muscle. Biceps femoris hypertrophy and, in males only, semimembranosus hypertrophy was observed following the ACL reconstruction. The lack of semimembranosus hypertrophy in the women could, via tibial internal rotation torque deficit, contribute to the less favorable functional and subjective outcome recorded for the women. The results indicate that the quadriceps, the combined knee flexor/tibial internal rotator muscles, side of ACL injury, and sex are important to consider in rehabilitation after STG graft.

X-ray phase-contrast CO(2) angiography for sub-10 µm vessel imaging.

X-ray in-line phase contrast has recently been combined with CO(2) angiography for high-resolution small-animal vascular imaging at low radiation dose. In this paper we further investigate the potential and limitations of this method and demonstrate observation of vessels down to 8 µm in diameter, considerably smaller than the 60 µm previously reported. Our in-line phase-contrast imaging system is based on a liquid-metal-jet-anode x-ray source and utilizes free-space propagation to convert phase shifts, caused by refractive index variations, into intensity differences. Enhanced refractive index variations are obtained through injection of CO(2) gas into the vascular system to replace the blood. We show rat-kidney images with blood vessels down to 27 µm in diameter and mouse-ear images with vessels down to 8 µm. The minimum size of observable blood vessels is found to be limited by the penetration of gas into the vascular system and the signal-to-noise ratio, i.e. the allowed dose. The diameters of vessels being gas-filled depend on the gas pressure and follow a simple model based on surface tension. A theoretical signal-to-noise comparison shows that this method requires 1000 times less radiation dose than conventional iodine-based absorption contrast for observing sub-50 µm vessels.