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In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNVuses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNValso reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNVenables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.

ObjectiveTo compare in images, obtained by high-resolution peripheral quantitative computed tomography (HR-pQCT) and conventional radiography (CR) of the second and third metacarpophalangeal (MCP) joints, the minimal erosive cortical break needed to differentiate between pathological and physiological cortical breaks.MethodsIn this single-center cross-sectional study, patients with established rheumatoid arthritis (disease duration ≥ 5 yrs) had their second and third MCP joints of the dominant hand investigated by HR-pQCT and CR. Empirical estimation was used to find the optimal cut-off value for the number of erosions and total erosive volume, which were detectable between patients with and without erosions in the second and third MCP joints according to CR.ResultsThe total erosive volume in the second and third MCP joints by HR-pQCT for CR-detected erosive disease was estimated to be 56.4 mm3(95% CI 3.5-109.3). The sensitivity and specificity at this cutpoint were 78% and 83%, respectively, with an area under the receiver-operating characteristic curve (AUC) of 0.81. The optimal cut-off value for the number of erosions by HR-pQCT was 8.5 (95% CI 5.9-11.1) for CR-detected erosive disease in the second and third MCP joints. The sensitivity and specificity at this cutpoint were 74% and 88%, respectively, with an AUC of 0.81.ConclusionErosions by HR-pQCT were larger in patients with erosive damage in the second and third MCP joints by CR. We found that CR had poor sensitivity for detecting erosive disease when the erosive volume was < 56.4 mm3or the number of erosions was < 8.5.

•Denmark was one of the first countries to implement universal screening for defective mismatch-repair (dMMR) in colorectal cancer. Implementation rates and completeness of the screening cascade remains undefined.•A decade of national, population-based registries of universal dMMR screening in colorectal cancer was accessed in terms of uptake rate, detection rate and referral to genetic counselling and/or genetic diagnostics.•The study shows high uptake of dMMR analysis, but reveals disparities in access related to sex, age, tumour location and health care provider. Referral to genetic counselling and/or diagnostics in accordance with clinical guidelines for hereditary cancer was suboptimal.•These findings have practice implications related to equity of care and missed opportunities for cancer prevention and early diagnostics due incomplete diagnostic work-up.•The results provide added value for decision-makers and health professionals related to the design and monitoring of dMMR screening programs in cancer to ensure robust and resource-efficient implementation.

To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants.

Background. Occupational therapists are generally positive towards use of measuring tools. However, such use may be problematic.Purpose. To illuminate hidden and adverse effects of using measuring tools in occupational therapy.Method. A Foucauldian inspired thematic analysis of the use of measuring tools in 13 reports of practice development projects in Denmark.Findings. Three themes were constructed: “Categorisation of loss”, “Conduct of conduct: Self-tracking and competition”, and “Conforming to expected forms of everyday living”. Measuring tools tended to produce generalised truths about older adults and were used to predict outcome of or access to reablement programs. The measurements guided both older people and professionals, and measurements created both motivation and resistance. The tools served as an extension of the healthcare professionals’ authority.Implications. When appropriately situated, measuring tools have the potential to empower and enhance older adults’ lives and should be the focus of greater clinical attention.

Cardiac CT can be used to evaluate fracture rate by assessing the bone mineral density of thoracic vertebrae.

Severe urinary tract infections are commonly caused by sub-strains of Escherichia colisecreting the pore-forming virulence factor α-hemolysin (HlyA). Repeated or severe cases of pyelonephritis can cause renal scarring that subsequently can lead to progressive failure. We have previously demonstrated that HlyA releases cellular ATP directly through its membrane pore and that acute HlyA-induced cell damage is completely prevented by blocking ATP signaling. Local ATP signaling and P2X7receptor activation play a key role in the development of tissue fibrosis. This study investigated the effect of P2X7receptors on infection-induced renal scarring in a murine model of pyelonephritis. Pyelonephritis was induced by injecting 100 million HlyA-producing, uropathogenic E. coliinto the urinary bladder of BALB/cJ mice. A similar degree of pyelonephritis and mortality was confirmed at day 5 after infection in P2X7+/+and P2X7−/−mice. Fibrosis was first observed 2 weeks after infection, and the data clearly demonstrated that P2X7−/−mice and mice exposed to the P2X7antagonist, BBG, show markedly less renal fibrosis 14 days after infection compared with controls (P < 0.001). Immunohistochemistry revealed comparable early neutrophil infiltration in the renal cortex from P2X7+/+and P2X7−/−mice. Interestingly, lack of P2X7receptors resulted in diminished macrophage infiltration and reduced neutrophil clearance in the cortex of P2X7−/−mice. Hence, this study suggests the P2X7receptor to be an appealing antifibrotic target after renal infections.

Cell designs that integrate membrane-electrode assemblies (MEAs) with highly selective catalysts are a promising route to reduce ohmic losses and achieve high energy efficiency in CO2reduction at industrially relevant current densities. In this work, porous silver filtration membranes are demonstrated as simple and efficient gas-diffusion electrodes for CO2reduction to CO at high current densities in an MEA-type device. A partial current density for CO of up to ca. 200 mA cm–2was achieved at a cell voltage of ca. 3.3 V, in tandem with minimal H2production. However, the analysis of cathodic and anodic outlet streams revealed that CO2cross-over across the anion-exchange membranes, mostly in the form of CO32–but partially as HCOO–generated over the cathode, actually exceeds the amount of CO2converted to the target product, resulting in a poor utilization of the reactant and in the early onset of mass transfer limitations. In addition, CO2cross-over leads to a nonstoichiometric decrease of the outlet flow rate from the cathodic compartment. This effect can lead to a substantial overestimation of catalytic performance if the inlet flow rate of CO2is used as reference for calculating partial current densities and Faradaic efficiencies. The results of this work highlight the importance of carrying out a carbon balance, in addition to traditional measurements of activity and selectivity, to adequately assess the performance of CO2reduction devices at high current densities, and inform future efforts aimed at mitigating membrane cross-over in MEA-type electrolyzers for CO2reduction.

Background and Aims: The risk of synchronous and metachronous colorectal cancer is influenced by heritable and environmental factors. As a basis for comparative studies, we provide population-based estimates of synchronous and metachronous colorectal cancer with a focus on non-heritable cases.Material and Methods: Based on data from national Danish cancer registers, we estimated the proportion of synchronous colorectal cancer and the incidence rates and risks for metachronous colorectal cancer in 28,504 individuals, who developed 577 metachronous colorectal cancer above age 50.Results: Synchronous colorectal cancer was diagnosed in 1.3% of the cases. The risk of metachronous colorectal cancer was associated with sex, tumor location, and age with the strongest influence from the latter. The incidence rate ratios for metachronous colorectal cancer ranged from above 6 in patients below age 65 to <1–3.2 in patients above age 65. The absolute risk of metachronous colorectal cancer was ⩾10% in patients below age 65 and 1.0%–8.0% in patients above age 65.Conclusion: Individuals who develop sporadic, non-inherited colorectal cancer above age 50 are at a significantly increased risk of metachronous colorectal cancer with risk estimates that are strongly affected by age. This observation underscores the need for development of targeted surveillance in the most common clinical subset of colorectal cancer.

Background: Diagnosing patients with giant cell arteritis (GCA) remains difficult. Due to its non-specific symptoms, it is challenging to identify GCA in patients presenting with symptoms of polymyalgia rheumatica (PMR), which is a more common disease. Also, commonly used acute-phase markers CRP and ESR fail to discriminate GCA patients from PMR and (infectious) mimicry patients. Therefore, we investigated biomarkers reflecting vessel wall inflammation for their utility in the accurate diagnosis of GCA in two international cohorts. Methods: Treatment-naïve GCA patients participated in the Aarhus AGP cohort (N= 52) and the Groningen GPS cohort (N= 48). The AGP and GPS biomarker levels and symptoms were compared to patients presenting phenotypically as isolated PMR, infectious mimicry controls and healthy controls (HCs). Serum/plasma levels of 12 biomarkers were measured by ELISA or Luminex. Results: In both the AGP and the GPS cohort, we found that weight loss, elevated erythrocyte sedimentation rate (ESR) and higher angiopoietin-2/-1 ratios but lower matrix metalloproteinase (MMP)-3 levels identify concomitant GCA in PMR patients. In addition, we confirmed that elevated platelet counts are characteristic of GCA but not of GCA mimicry controls and that low MMP-3 and proteinase 3 (PR3) levels may help to discriminate GCA from infections. Conclusion: This study, performed in two independent international cohorts, consistently shows the potential of angiopoietin-2/-1 ratios and MMP-3 levels to identify GCA in patients presenting with PMR. These biomarkers may be used to select which PMR patients require further diagnostic workup. Platelet counts may be used to discriminate GCA from GCA look-alike patients.

The ocean is hypothesized to be where life on earth originated, and subsequent evolutionary transitions between marine and terrestrial environments have been key events in the origin of contemporary biodiversity. Here, we review how comparative genomic approaches are an increasingly important aspect of understanding evolutionary processes, such as physiological and morphological adaptation to the diverse habitats within the marine environment. In addition, we highlight how population genomics has provided unprecedented resolution for population structuring, speciation and adaptation in marine environments, which can have a low cost of dispersal and few physical barriers to gene flow, and can thus support large populations. Building upon this work, we outline the applications of genomics tools to conservation and their relevance to assessing the wide-ranging impact of fisheries and climate change on marine species.

Extractive foreign direct investment (FDI) is heralded as the new development opportunity in Africa. A key precondition for FDI's contribution, however, is that foreign investors create ‘local content’ by linking up to the local economy. Consequently, African host governments are contemplating ways in which they can promote local content. This paper examines local content policies and practices in three African countries – Tanzania, Uganda and Mozambique – all countries with huge expectations for extractive based economic development. It is found that in spite of high ambitions and strong expectations, local content is limited, shallow and inefficient. The paper explores why local content apparently is so difficult to achieve in these African countries. It is argued that conventional economic explanations, focusing on market failures and weak institutions, are partial at best and therefore must be complemented with political explanations. Hence, it is proposed that local content practices in the three countries can be understood partly as the results of ruling elites’ efforts to build and maintain stable political coalitions.

Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.

Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.

Intrauterine growth restriction (IUGR) occurs naturally in pigs and leads to low birth weight of piglets due to undernutrition caused by placental insufficiency. For 2 main reasons, low birth weight causes economic loss. First, low birth weight pigs have a greater mortality and increasing the litter size causes more low birth weight piglets within litters. Second, surviving low birth weight piglets have reduced performance (i.e., ADG, feed conversion rate, and percentage meat). To develop dietary strategies for preventing IUGR, knowledge of the biological basis of IUGR is required. Muscle fiber number, formed during myogenesis, is correlated positively with performance traits and has been shown in several studies to be reduced in low birth weight pigs. Postnatal muscle hypertrophy is due to satellite cell number per fiber at birth and their rate of proliferation as well as protein deposition (i.e., protein synthesis and degradation). Previous studies and some recent ones indicate that low birth weight littermates in mice are born with fewer satellite cells and studies on pigs show that the rate of satellite cell proliferation may vary within litters. Proteomics studies show that protein synthesis and degradation is downregulated in IUGR pigs and low birth weight pigs also produce meat with less tenderness. Alternative maternal feeding strategies to prevent IUGR have been examined. Increasing maternal global nutrition had no beneficial effect on performance and muscle growth traits in several studies. Feeding excess maternal dietary protein also did not influence muscle growth traits whereas moderately decreased maternal dietary protein may decrease muscle fiber number and performance. On the other hand, addition of L-carnitine to the maternal gestation or lactation diet may increase birth and weaning weights or the muscle fiber number, respectively, in low birth weight pig offspring. Finally, promising data have been obtained on reproductive traits in pigs after addition of functional AA, such as arginine and glutamine, to the gestational diet. Although much is known about the biological basis of IUGR, we still need to learn much more about the mode of action before maternal dietary strategies can be developed to prevent IUGR.

Objectives.Head and neck cancer is frequent in the Inuit population of Greenland and is characterized by a very high incidence of Epstein-Barr virus associated nasopharyngeal carcinoma (NPC). However, information on the treatment and survival of Inuit head and neck cancer patients is practically non-existent. The aim of this study, therefore, was to analyse the epidemiological pattern, time course and survival of head and neck cancer patients in Greenland.Study design.Retrospective register-based study.Methods.The Danish Civil Registration System, the Danish Cancer Registry and hospital-based registries were used to identify all patients resident in Greenland diagnosed with head and neck cancer during the period 1994–2003. Data were analysed with regard to clinical characteristics, treatment delay and survival.Results.A total of 125 patients were identified. The age-standardized incidence rate for all head and neck cancer cases was 28/100,000 for males and 19/100,000 for females. High incidence rates were found for NPC and oral cancers. Of all cancers, 47% were stage IV at the time of diagnosis, while 61% of all NPC’s were stage IV. The median delay from date of first symptom to treatment was 248 days for all cancers. The overall crude 5-year survival rate for all sites together was 35% and for NPC 20%.Conclusion.Survival of head and neck cancer in Greenland is very low. Delays in treatment and inadequate follow-up on treatment complications are probable causes. The improvements in treatment for NPC and other head and neck cancer cases over the last decades are yet to be seen in this Inuit population.

The current pork slaughter process is primarily optimized to reduce cooler shrink and the incidence of PSE pork. Elimination of the halothane gene and improved preslaughter handling have decreased the incidence of PSE pork and improved the water-holding capacity of the muscle; however, the chilling process has not been optimized to accommodate these changes. The hypothesis that stepwise chilling could improve tenderness without compromising water-holding capacity was tested in this study. The stepwise chilling treatments were composed of a rapid chilling to 10 or 15°C (in a chilling tunnel) and a 6-h holding period at 10 or 15°C, followed by rapid chilling to 4°C. Both treatments were compared directly with a chilling treatment that simulated conventional tunnel chilling; one carcass half from each pig was allocated to a stepwise chilling treatment, whereas the other carcass half was allocated to the control treatment. A total of 42 pigs were slaughtered on 6 slaughter days. Biopsies were collected for analysis of glycogen degradation and glycogen debranching enzyme activity from slaughter until 72 h postmortem, and samples for color, sarcomere length, drip loss, Warner-Bratzler shear force, and sensory analysis were removed from the carcass 24 h postmortem. Substantial temperature differences were obtained during the holding period between the stepwise and conventionally chilled carcass halves. These had almost, but not completely, disappeared by 22 h postmortem, and although the differences were small, pH was significantly (P< 0.01) less in the stepwise-chilled carcasses compared with the control carcasses. The stepwise chilling treatments led to significantly improved (P< 0.01) tenderness in LM without compromising quality indicators or attributes such as pH, drip loss, or ham processing yield, although color of the stepwise-chilled pork was affected. Neither the tenderness of processed semimembranosus muscle nor the shear force of biceps femoris muscle was affected (P> 0.05) because of the smaller temperature differences in these muscles. The improvements in tenderness could be solely attributed to the increased proteolysis postmortem in the stepwise-chilled carcasses, with the greater temperatures favoring proteolytic enzymes involved in muscle protein degradation. Furthermore, the results for glycogen metabolism successfully revealed that both pro- and macroglycogen contributed to the energy generation in postmortem muscles, with degradation of both forms early postmortem.

Background and objective: Gallstones are highly prevalent, and more than 9000 cholecystectomies are performed annually in Denmark. The aim of this guideline was to improve the clinical course of patients with gallstone disease including a subgroup of high-risk patients. Outcomes included reduction of complications, readmissions, and need for additional interventions in patients with uncomplicated gallstone disease, acute cholecystitis, and common bile duct stones (CBDS).Methods: An interdisciplinary group of clinicians developed the guideline according to the GRADE methodology. Randomized controlled trials (RCTs) were primarily included. Non-RCTs were included if RCTs could not answer the clinical questions. Recommendations were strong or weak depending on effect estimates, quality of evidence, and patient preferences.Results: For patients with acute cholecystitis, acute laparoscopic cholecystectomy is recommended (16 RCTs, strong recommendation). Gallbladder drainage may be used as an interval procedure before a delayed laparoscopic cholecystectomy in patients with temporary contraindications to surgery and severe acute cholecystitis (1 RCT and 1 non-RCT, weak recommendation). High-risk patients are suggested to undergo acute laparoscopic cholecystectomy instead of drainage (1 RCT and 1 non-RCT, weak recommendation). For patients with CBDS, a one-step procedure with simultaneous laparoscopic cholecystectomy and CBDS removal by laparoscopy or endoscopy is recommended (22 RCTs, strong recommendation). In high-risk patients with CBDS, laparoscopic cholecystectomy is suggested to be included in the treatment (6 RCTs, weak recommendation). For diagnosis of CBDS, the use of magnetic resonance imaging or endoscopic ultrasound prior to surgical treatment is recommended (8 RCTs, strong recommendation). For patients with uncomplicated symptomatic gallstone disease, observation is suggested as an alternative to laparoscopic cholecystectomy (2 RCTs, weak recommendation).Conclusions: Seven recommendations, four weak and three strong, for treating patients with symptomatic gallstone disease were developed. Studies for treatment of high-risk patients are few and more are needed.Endorsement: The Danish Surgical Society.

Objective:To determine the predictive value of sentinel node biopsy (SNB)‐assisted neck dissection in patients with oral squamous cell carcinoma (SCC) stage T1 to 2N0M0 and to determine the incidence of subclinical metastases.

The relationship between the inundation of a salt marsh in southeast Denmark not subject to lunar tides and the availability and predation of seeds of the annuals Salicorniaspp. and Suaéda maritimaby autumn staging dabbling ducks was studied by carrying out exclosure experiments over the course of 2 years. There was a marked difference in the wetness of the salt marsh between the two study years, which resulted in distinct temporal patterns of salt-marsh use by dabbling ducks. In both years, the depletion of seeds of both Salicorniaspp. and S. maritimawas initiated subsequent to the flooding of the sample transects, which also induced the gradual release of seeds from the plants within the exclosures. Nevertheless, seeds were removed more rapidly in plots visited by dabbling ducks than in the exclosures. The predation of seeds took place as soon as the individual plants had been fully submerged, but before the seeds were released from the plants. The timing of flooding events during early autumn may potentially affect the availability of the salt-marsh seed stock. Therefore, weather conditions may impose critical constraints on the feeding opportunities for dabbling ducks during autumn migration on non-tidal salt marshes.

Sixteen female pigs (Duroc × Landrace × Large White) were divided into 2 groups, which had either free access to the diet (control group) or were feed-restricted from d 28 to 80 and then had free access to the diet (compensatory growth group). The sensory analysis showed that the pigs exhibiting compensatory growth produced meat with increased tenderness compared with control pigs (P< 0.05). To gain further knowledge of the influence of compensatory growth on meat tenderness, the sarcoplasmic protein fraction of muscle tissue was studied at the time of slaughter and 48 h postmortem using proteome analysis. At slaughter, 7 different proteins were found to be affected by compensatory growth: HSC70, HSP27, enolase 3, glycerol-3-phosphate dehydrogenase, aldehyde dehydrogenase E2, aldehyde dehydrogenase E3, and biphosphoglycerate mutase. The HSC70 and HSP27 both belong to the heat shock family and are known to play a role during muscle development. Hence, they may be affected by compensatory growth and increased protein turnover. Forty-eight hours after slaughter, 8 different proteins were found to be affected by compensatory growth: myosin light chain (MLC) II, MLC III, sulfite oxidase, chloride intracellular channel 1, 14-3-3 protein γ, elongin B, and phosphohistidine phosphatase 14. The changes observed on MLC II and MLC III could be a consequence of enzymatic cleavage in the neck region of the globular myosin head domain that causes the release of MLC II and MLC III from the actomyosin complex. It has previously been hypothesized that compensatory growth results in an increased postmortem proteolysis; thus it was presumed that the intensity of some protein fragments would be affected by compensatory growth. However, the peptides that were found to be affected at 48 h postmortem were all full-length proteins. The 14-3-3 protein γ has been proposed to play a role in the contraction of muscle during rigor and may thereby have an effect on meat tenderness. This study reveals some very interesting changes in the muscle proteome affected by compensatory growth, which may be useful in understanding the relationship among compensatory growth, protein turnover, and meat tenderness.

Our objective was to evaluate whether small (biopsy-sized) samples could be used to measure calpain and calpastatin activities in skeletal muscle. The accuracy of different separation and assay methods for the quantification of calpains and calpastatin from small (1.0 and 0.2 g) skeletal muscle samples was tested. In Exp. 1, the LM was removed from six lambs, and a 50-g subsample was processed using the reference method (DEAE-Sephacel chromatography and casein assay). Subsamples (1.0 and 0.2 g) also were processed using the two-step separation (1 mL DEAE-Sephacel and bulk elution using 200 and 400 mMNaCl) and heated calpastatin methods; in both cases, fractions were assayed with Bodipy-labeled and [14C]-labeled casein microassays. Finally, casein zymography was used to separate and quantify the calpain proteases from 1.0-and 0.2-g samples. The values obtained after processing the 50-g sample using the reference method were judged most accurate, and the alternative approaches were compared with these. For each extraction and assay approach, we considered: 1) the effect of the sample size on the mean activity; 2) increased or decreased variation of data; and 3) the correlation relative to the reference method. Where possible, we compared the ratio of calpain to calpastatin activities determined using the alternative approaches with the ratios found using the reference method. These methodologies were further investigated in Exp. 2, where single homogenates from different tissues (heart, spleen, lung, and muscle) were assayed using the alternative approaches. Experiment 1 established that most of the approaches suffered from poor correlations and/or unacceptable variation. By using a large, homogenous sample in Exp. 2, however, we determined that this error was not due to the methodologies themselves. Therefore, the unacceptable variation found in Exp. 1 resulted from the small sample size, and we recommend that large tissue samples (e.g., 50 g) should be used for calpain and calpastatin activity measurements in skeletal muscle instead of small tissue biopsies (e.g., 0.2 and 1.0 g).

Compensatory growth is a phenomenon observed in pigs given free access to feed following a period of restricted feeding that results in increased growth rates. Compensatory growth is believed to increase protein turnover and thereby the proteolytic potential at the time of slaughter, leading to faster tenderization rates of meat. Nine litters of three gilts and three barrows were allocated within litter and gender to three dietary treatment groups. Pigs had ad libitum access to feed from d 28 to slaughter at d 140 (ALA) or were restricted to 69% ad libitum from d 28 to d 80 or 90, and then given ad libitum access to the diet until slaughter at d 140 (RA80 and RA90, respectively). Pigs in the RA80 and RA90 treatment groups had a 9.7% higher (P⩽ 0.001) fractional growth rate in the second feeding period than those in the ALA group. Growth rate was correlated to the activity of m-calpain (r = 0.37; P⩽ 0.01), β-glucuronidase (r = 0.48; P⩽ 0.001), and cathepsins B (r = 0.47; P⩽ 0.001) and B+L (r = 0.31; P⩽ 0.04). The LM of RA80-gilts received higher tenderness scores than the LM of ALA gilts, but tenderness scores were similar among barrows regardless of treatment (gender × treatment; P= 0.02). Conversely, tenderness scores were higher for the biceps femoris of ALA barrows than either ALA gilts or RA90 barrows (gender × treatment; P= 0.02). Desmin and troponin-T degradation, as well as myofibrillar fragmentation index, of the LM were not (P⩾ 0.24) affected by treatment. No dietary treatment effects were observed on the activities of μ-calpain (P= 0.15), m-calpain (P= 0.74), or calpastatin (P= 0.91) at slaughter. The cathepsin inhibitors, cystatins, tended to be increased (P= 0.06) in RA80 and RA90 pigs. Sarcomere length was longer (P= 0.003) in the LM of gilts than barrows. Barrows in the RA80 group had lower i.m. fat concentrations than ALA; however, no differences were found in the LM of gilts (gender × treatment; P= 0.03). The underlying hypothesis that compensatory growth leads to an increased proteolytic potential at the time of slaughter could not be verified in this study.

AbstractAccording to standard New Public Management propositions a (semi) autonomous revenue authority is a remedy for many problems that plague the public sector, such as multiple layers of principals and agent, Byzantine rules, low pay, and poor and distorted incentives, which all contribute to unfair and inefficient revenue collection. The Uganda Revenue Authority (URA), established in 1991, is the oldest of its kind in sub-Saharan Africa. The analyses presented in this article indicate that URA autonomy initially increased but later declined. Paradoxically, real autonomy attracts political and bureaucratic attention that may, in turn, undermine it. Thus the decline in the URA's autonomy has come both from below, with the loss of the agency's legitimacy from the perspective of taxpayers, and from above, with a loss of formal and informal authority vis-à-visthe Ministry of Finance and state elites. The President's role in the decline of URA autonomy has been especially significant. That of donors has been ambiguous—strengthening the agency's autonomy in some respects, weakening it in others. In addition, autonomy has been eroded as a consequence of declining staff motivation and clientelistic personnel practices. Revenue collection has suffered as a result.

In this paper, we report two new simple field methods to assess changes in pectoral muscle mass in live moulting geese. In the first method, transverse chest profiles of Canada geese Branta canadensisand greylag geese Anser anserwere recorded using soldering wire. This standard measure of the chest angle showed a highly significant relationship with actual pectoral muscle mass. Chest angle measures showed a highly significant polynomial correlation with an index of moult stage, i.e. length of the ninth primary (p9). This indicated an initial slight decline in pectoral muscle mass as p9 length increased, followed by an increase in muscle mass in preparation for regaining the ability to fly. In the second method, visual pectoral profile scores from 0 (thin pectoral muscles concave) to 3 (convex bulky) recorded at distances using telescope or binoculars also proved to be useful as a field measure of pectoral muscle mass in moulting geese. Hence, the first method provides a non-consumptive means of predicting pectoral muscle mass in moulting geese without the need to dissect birds, and the second method enables field prediction of muscle mass in moulting geese without resort to capture of birds.

The effects of various growth rates in pigs induced by four different feeding strategies on the activity of the calpain system and on postmortem (PM) muscle proteolysis and tenderness development were studied. An increased growth rate may be caused by an increased protein turnover, which results in up-regulated levels of proteolytic enzymes in vivo that, in turn, possibly will affect PM tenderness development. It can be hypothesized that increased proteolytic activity preslaughter will increase the PM tenderization rate. From postnatal d 28 to d 90 (phase 1) the pigs were divided into two groups, given either ad libitum (A) or restricted (R, 60% of ad libitum) access to feed. The two groups were then divided into two subgroups, given either restricted or ad libitum access to feed from d 91 to slaughter at d 165 (phase 2). Measurements of the activity of μ-calpain, m-calpain, and calpastatin; concentrations of total collagen and the percent of soluble collagen; and RNA, DNA, and elongation factor-2 where made at slaugther. Myofibrillar fragmentation index (MFI) was determined at slaughter and 24 h PM. Warner-Braztler shear force was determined 1 d and 4 d PM. Pigs fed restricted diets in phase 1 and fed ad libitum in phase 2 (RA pigs) had increased growth rates in the last phase compared to pigs fed ad libitum during both phase 1 and phase 2 (AA pigs). The increased growth rate (compensatory growth) was followed by an increased proteolytic potential (μ-calpain:calpastatin ratio), increased MFI values, and higher tenderization rates. There was a positive correlation between the activities of m-calpain and growth rates (r = 0.35, P= 0.03), and between RNA levels and growth rates (r = 0.43, P= 0.006). The proposed hypothesis is largely supported by the results. The activities of both μ- and m-calpain at slaughter were highest in fast-growing pigs. The calpain activity was highest in RA pigs, which in turn also had the fastest growth rates prior to slaughter among the four groups. This implies that the synthesis of these enzymes was up-regulated during the second feeding period to a larger extent in RA pigs. The proteolytic potential and the MFI values indicate that the up-regulated in vivo calpain activity had an effect on PM protein degradation, which also is supported by the higher tenderization rate in RA pigs.

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty-three rats were randomised to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n-6 (17.7 ± 0.6; 16.4 ± 0.4 % of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n-3 (2.9 ± 0.1 and 2.7 ± 0.1 % of total fatty acids, respectively) was uniformly higher across groups (P &lt; 0.02) with no differences between diet groups. The proportion of long chain polyunsaturates was also significantly higher in the eccentrically contracted (39.9 ± 0.6 % of total fatty acids) compared to the control leg (38.2 ± 0.6 % of total fatty acids; P &lt; 0.01). In contrast no differences were observed in the fatty acid composition of the triacylglycerols stored within the muscle. Thus one severe bout of eccentric contractions modulates the fatty acid composition of the muscle membrane phospholipids when compared to a control leg, and supplemental intake of fish oil or vitamin C did not attenuate this effect. Experimental Physiology (2001) 86.5, 599-604.

This study investigated if prior eccentric contractions, and thus mechanical strain and muscle damage, exert an effect on the muscle membrane phospholipid fatty acid composition in rats, and whether a possible effect could be attenuated by dietary supplements. Twenty‐three rats were randomised to three groups who received chow with added fish oil (n = 8), vitamin C (n = 8) or no supplement (n = 7). After 3 weeks of feeding, calf muscles on one side were stimulated electrically during anaesthesia causing eccentric contractions. Two days later the white gastrocnemius, a part of the stimulated calf muscle, was excised from both legs. In the muscles stimulated to contract eccentrically, compared to the control muscles, the proportion of arachidonic acid, C20:4,n‐6 (17.7 ± 0.6; 16.4 ± 0.4% of total fatty acids, respectively) and docosapentanoeic acid, C22:5,n‐3 (2.9 ± 0.1 and 2.7 ± 0.1% of total fatty acids, respectively) was uniformly higher across groups (P < 0.02) with no differences between diet groups. The proportion of long chain polyunsaturates was also significantly higher in the eccentrically contracted (39.9 ± 0.6% of total fatty acids) compared to the control leg (38.2 ± 0.6% of total fatty acids; P < 0.01). In contrast no differences were observed in the fatty acid composition of the triacylglycerols stored within the muscle. Thus one severe bout of eccentric contractions modulates the fatty acid composition of the muscle membrane phospholipids when compared to a control leg, and supplemental intake of fish oil or vitamin C did not attenuate this effect.

The purpose of this article is to provide a critical review of some recent, comparative and longitudinal studies of various aspects of tax—aid—democracy linkages in poor aid-dependent African countries. Each study represents various perspectives on this, namely the importance of economic structure; of regime type and incentives; of political institutions; and of the political economy of aid. The main features and problems of each approach are highlighted, and five issues central to a better understanding of tax—aid—democracy linkages are identified: the extent of informalisation of the economy structure (not just the sectoral composition of GDP); the reciprocity between taxation and service provision (the importance of which may be overrated in current literature on taxation); the composition and conditionality of aid (not just its relative size); and the extent of coercion and conflict in taxation (especially in local government taxation, which affect many more citizens than central government taxation does).

The aim of the present study was to investigate whether muscle glycogen stores in slaughter pigs could be decreased through strategic finishing feeding before slaughter. Moreover, preliminary meat quality traits were measured to see whether such a regulation of muscle glycogen stores affected ultimate pH, color, and tenderness in the meat. The strategic finishing feeding was carried out the last 3 wk prior to slaughter. Seven experimental groups with eight animals per group were fed diets low in digestible carbohydrates. A control group with four animals was fed a traditional grower-finishing diet. The muscle glycogen stores were reduced in longissimus muscle (LM) 11 to 26% at the time of slaughter in pigs that were fed the experimental diets compared with the control group. Meat quality measured as ultimate pH and color on LM muscle in half the pigs 24 h postmortem showed that ultimate pH in LM was not affected by the reduction in glycogen stores in the muscles from pigs fed any of the experimental diets. However, the meat from pigs fed the experimental diets was darker than the meat from pigs that were fed the control diet with two of the experimental diets, resulting in significantly lower L* values. Activities of key enzymes in the glycolytic pathway, glycogen phoshorylase a and b, phosphofructokinase, and the fatty acid oxidative pathway, β-hydrozyacyl-CoA-dehydrogenase, were not affected by the strategic feeding. In contrast, the activity of the proteolytic enzyme calpain as well as its inhibitor calpastatin was influenced by the strategic feeding. Lower activity of μ-calpain and greater activity of calpastatin in the muscle samples from the strategically fed pigs indicate a lesser muscle protein degradation in the muscles compared with muscles of control animals. The present study showed that the muscle glycogen stores in slaughter pigs can be reduced at the time of slaughter through strategic finishing feeding with diets low in digestible carbohydrate without compromising growth rate.

Abstract: Purpose: The purpose of this study was to elucidate the potential of human breast cancer cells (BCC) to induce matrix degradation and neo-vascularization, essential for continued tumor growth, in osteolytic lesions. Methods: BCC were inoculated into the left cardiac ventricle of female athymic mice and osteolytic lesions were radiologically visualized within 4 weeks from inoculation. Results: Histomorphometric analysis of bone sections revealed a significant increase in the number and maturity of osteoclasts (OCl) lining the bone surfaces next to tumor tissue when compared to corresponding bone surfaces in healthy mice. In addition, a large number of newly formed blood vessels could be visualized by immunohistochemistry at the periphery of and within tumor tissue. When bone marrow (BM) cells were cultured in the presence of BCC the OCl formation was increased threefold. These OCl were also found to be more mature and to have greater resorptive activity. Moreover, BCC were found to stimulate proliferation, migration, and differentiation of BM-derived endothelial cells. Conclusions: Matrix destruction and neo-vascularization are accomplished by BCC arrested in the BM cavity by increasing recruitment and activity of OCl and by induction of angiogenesis within or in proximity to the tumor tissue.

An alternative to the so-called ‘marker substance’ method used to estimate daily food intake in geese is presented. Based on the assumption that a grazing bird takes one leaf per peck, the daily food intake rate can be calculated by multiplying mean bite weight, peck rate and total daily foraging time. Wintering pink-footed geese Anser brachyrhynchusfeeding on pastures and winter wheat fields were collected and samples of leaves in the oesophagus were measured, dried and weighed individually. We measured leaf lengths in unexploited areas of the same fields upon which geese had been feeding. Peck rates of winter wheat feeding geese were measured. Daily foraging time was obtained from observations of activity budgets of flocks of geese. Daily food intake of winter wheat feeding geese was estimated at 159–229 g ash free dry weight (AFDW) during late winter and at 188–212 g AFDW in early spring. For geese feeding on pastures in early spring food intake was estimated at 170 g AFDW. Averages were generally in accordance with estimates derived by the ‘marker substance’ method. Bite length was positively related to primary leaf length of winter wheat, suggesting that geese adjust bite size to available leaf lengths. There was a negative relationship between peck rate and length of all leaf types, but the relationship was only significant for primary leaves. Based on the assumption that bite length was identical to primary leaf length and the relationship between primary leaf length and peck rate, a quadratic relation between primary leaf length and instantaneous intake rates was derived, yielding a peak intake rate of 0.62 g AFDW min-1at a primary leaf length of 8.4 cm. In the beginning of the winter, bite lengths were close to this optimal leaf length, but decreased during winter.

Traditionally, pink-footed geese Anser brachyrhynchuswintering in Denmark, the Netherlands and Belgium have used the Danish sites only during mild winters, rapidly moving southwards in case of cold spells. Since the 1980s, an increasing number of geese have remained on the Danish wintering grounds despite cold spells, foraging on pastures and winter wheat Triticum aestivumfields. We compare the daily time and energy budgets and the food quality in the two habitats during winter. Winter wheat fields were increasingly used by the geese as temperatures dropped. At temperatures around 0°C, the geese foraged in both habitats, spending on average 83.8% and 74.9% of the daytime foraging in pastures and winter wheat, respectively. The estimated daily energy expenditure was slightly higher on pastures than on winter wheat fields (1,076 vs 1,057 kJ). The estimated daily food intake determined using the ‘marker substance’ method was 148 and 157 g ash free dry weight (AFDW) in geese feeding on pastures and winter wheat fields, respectively, equivalent to a daily net energy intake of 1,109 kJ and 1,145 kJ. Daily food intake, estimated on the basis of oesophagus contents of collected birds, was 170 g AFDW in pasture feeding geese and varied within 159–229 g AFDW in winter wheat feeding geese. In the mild winter, the protein content in winter wheat and Poadid not differ, whereas in the severe winter the protein content remained high in winter wheat but decreased in Poa.During the winters of 1994–1996, the abdominal profile index, API, in individually neck-banded geese observed repeatedly, only changed significantly during late January 1996. Neither during cold spells was there any change in API. Since the 1980s, the area covered by winter wheat has increased markedly in Denmark. Because winter wheat represents a reliable and profitable food source even in severe winters, the recent change in agricultural practice has enhanced the development of a new wintering strategy of pink-footed geese, allowing a northward expansion of their winter range. Potentially, this will increase the crop damage conflict and may lead to further population growth.

Mucin-type O-glycosylation is initiated by a large family of UDP-GalNAc: polypeptide N -acetyl-galactosaminyltransferases (GalNAc-transferases). Individual GalNAc-transferases appear to have different functions and Northern analysis indicates that they are differently expressed in different organs. This suggests that O-glycosylation may vary with the repertoire of GalNAc-transferases expressed in a given cell. In order to study the repertoire of GalNAc-transferases in situ in tissues and changes in tumors, we have generated a panel of monoclonal antibodies (MAbs) with well defined specificity for human GalNAc-T1, -T2, and -T3. Application of this panel of novel antibodies revealed that GalNAc- transferases are differentially expressed in different cell lines, in spermatozoa, and in oral mucosa and carcinomas. For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and GalNAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa. The expression patterns in normal oral mucosa were found to vary with cell differentiation, and for GalNAc-T2 and -T3 this was reflected in oral squamous cell carcinomas. The expression pattern of GalNAc-T1 was on the other hand changed in tumors to either total loss or expression in cytological poorly differentiated tumor cells, where the normal undifferentiated cells lacked expression. These results demonstrate that the repertoire of GalNAc-transferases is different in different cell types and vary with cellular differentiation, and malignant transformation. The implication of this is not yet fully understood, but it suggests that specific changes in sites of O-glycosylation of proteins may occur as a result of changes in the repertoire of GalNAc-transferases.

Simple mucin-type carbohydrate antigens Tn, sialosyl-Tn and T are often markers of neoplastic transformation and have very limited expression in normal tissues. We performed an immunohistological study of simple mucin-type carbohydrate antigens, including H and A variants, with well-defined monoclonal antibodies (MAb) on frozen and paraffin-embedded normal salivary gland tissue from 22 parotid, 14 submandibular, six sublingual, and 13 labial glands to elucidate the simple mucin-type glycosylation pattern in relation to cyto- and histodifferentiation. The investigated carbohydrate structures were predominantly observed in the cell cytoplasm, most often in the supranuclear area, suggesting localization to the Golgi region, whereas ductal contents were unstained. Mucous acinar cells expressed Tn, sialosyl-Tn, and H and A antigens, regardless of glandular location. Serous acinar cells, on the other hand, expressed A, H, and inconstantly sialosyl-T, Tn, and sialosyl-Tn antigens in major salivary glands, whereas serous cells of minor (labial) salivary glands expressed H exclusively, Tn and sialosyl-T antigens inconstantly, but never sialosyl-Tn and A antigens. The difference may be related to a more simple cytodifferentiation of serous cells of minor (labial) salivary glands as compared with major salivary glands. Duct cells in major salivary glands expressed A, H, and inconstantly T, sialosyl-T, and Tn antigens, whereas minor (labial) salivary glands ducts exclusively expressed H, T and sialosyl-T antigens, differences that may be related to dissimilarities in the duct system. Myoepithelial cells and basal cells exclusively expressed T and sialosyl-T antigens, which may prove useful in studies of salivary gland tumors, since these cells are known to play a key role in the histological characteristics of some salivary gland tumors. The results indicate a similar glycosylation pattern in the different major salivary glands, whereas minor (labial) salivary gland differ slightly in serous and duct cells. The limited and exclusive intracellular expression of the immature Tn, sialosyl-Tn, and T antigens indicates that these structures may be of value as markers of salivary gland tumors.

The value of malignancy grading of adenoid cystic carcinomas (ACC) is controversial. Some studies have shown that tumours with a solid growth component have a rapid fatal course, compared to tumours without a solid growth component, in which recurrences develop even many years after initial treatment. Other studies have failed to correlate growth patterns with clinical course. No universally accepted grading system exists and no reproducibility studies of the existing grading systems have been performed. The aim of this study was to examine the reproducibility of grading based on semi‐quantitative assessment of the solid growth pattern in ACC. Two different grading systems were assessed by 3 observers on a material of 59 ACC. Interobserver agreement was evaluated using the kappa statistic. The reproducibility of grading was poor, except for the category “solid component constituting 50% or more of the tumour” (kappa=0.52). It is concluded that quantitative methods are necessary if grading is to be used in prognostic evaluation of ACC. The rarity of the tumours, however, combined with difficulties in diagnosis will impede such investigations unless multicentre studies are undertaken.

Development of squamous cell carcinomas (SCCs) involves alterations in the adhesive interactions in the epithelium and invasion through the basement membrane. Therefore, changes in the expression of receptors and ligands involved in cell‐cell and cell‐matrix adhesion may be essential for the transformation of a premalignant into a malignant lesion. The aim of this study was to examine if expression of specific cell adhesion molecules can be used as markers of malignant development. By immunohistochemistry, we examined the expression pattern of integrins α2β1, α3β1, α6β4 and laminin‐5 in biopsies from SCCs (n=18), premalignant lesions (leukoplakias, n=21) and non‐premalignant tissue with chronic inflammation (n=11). In poorly differentiated SCCs, patchy loss of α3β1, α6β4 and laminin‐5 expression was pronounced at the invasion front, whereas there was a tendency to increased expression of α2β1. Analogous to the SCCs, biopsies from the leukoplakias and the non‐premalignant inflammatory tissue showed alterations of the expression of α3β1 and α6β4 in the basal cell layers and of laminin‐5. However, a characteristic finding in biopsies from leukoplakias was loss of α2β1 and α3β1 in the suprabasal cells. There was no unequivocal expression of the adhesion molecules distinguishing between inflammatory tissue, premalignant, and malignant lesions.

Single cell protein was produced from cassava starch by symbiotic growth of the α-amylase producing bacteria Bacillus subtilisand the yeast Candida utilis, which is accepted as fodder. By batch fermentations it was shown, that the pH fluctuation during the fermentation and the inoculum were extremely important parameters.

The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20–85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20 patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P=0.4l) and was independent of gender (P=0.61) and age (P=0.56), while thickness of the cellular epidermis decreased with age (P<0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness‐of‐fit for correlation r=0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.

The kinetics of the thrombin-catalysed release of fibrino-peptides A and B from human fibrinogen have been investigated and a mechanism correlating the release of fibrinopeptides to fibrin formation is presented. The sequential release of fibrinopeptides results in sequential activation of two sets of polymerisation sites.

The karyotypes 2n=48, 49 and 50 were in the breeding stock of Alopex species on a Danish fur farm represented in proportions 14-45-41%. Reproduction data is presented for 450 females of which 296 were mated with Alopex males and 154 used in interspecific crossing with Vulpes males. In Alopex×Alopex matings the age of the female had a significant effect on litter size. First year females averaged 1.3 pups less per litter than proven females. No effect of karyotype could be seen among young females. Among old females the karyotype 2n=49 reduced litter size with 0.7 pups per litter compared to karyotype 2n=50. In crossing with Vulpes males no consequent effect of age or karyotype was observed.

Hairy cell leukaemia is a form of leukaemia difficult to diagnose since pancytopenia is often present. Hairy cells contain tartrate-resistant acid phosphatase, and this factor is utilised in the diagnosis of the condition. This study confirms that it is also possible to demonstrate tartrate-resistant acid phosphatase in leukaemic infiltrates in formalin fixed paraffin-embedded tissue sections.

Fifteen laryngeal squamous cell carcinomas were investigated for the presence of transforming growth factor alpha (TGF-α) and epidermal growth factor (EGF) using immunohistochemical methods. In a recent study the same material was characterized for epidermal growth factor receptors (EGF receptors) which were confined predominantly to the undifferentiated cells. The expression of this growth factor system in malignant cells may play a role in carcinogenesis and/or tumour growth. All carcinomas were positive for TGF-α and 12 were positive for EGF. In moderately-to-well differentiated carcinomas, the immunoreactivity was mainly detected in the cytologically more differentiated cells. Nine sections included both laryngeal stratified squamous epithelium of normal appearance and carcinoma. The immunoreactivity was here again localized in the cytologically more differentiated cells above the basal cell layer. The present investigation and our previous results confirm the existence of EGF receptors, TGF-α and EGF in laryngeal carcinomas. In addition, we conclude that the conditions do exist for growth factors to act through an autocrine system in poorly differentiated tumours and through a paracrine system in the moderately-to-well differentiated tumours.