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Aims This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article: Bone Joint Res. 2020;9(5):202–210.

Primary lymphoma of the thyroid is an uncommon malignancy, whereas papillary thyroid carcinoma is the most common thyroid malignancy. Both have an association with Hashimoto's thyroiditis. We discuss a case of an 83 year old male who presented with a large neck swelling, which subsequently proved to be a primary thyroid lymphoma (extra-nodal marginal zone) with concurrent papillary thyroid carcinoma. These tumours manifested on a background of Hashimoto's thyroiditis. To date there have only been 13 other cases of joint papillary thyroid carcinoma and thyroid lymphoma within the literature. Our case report adds to this by discussing diagnosis, histopathological features and pitfalls in early detection.

A 51-year-old man presented with mild headache followed by sudden onset of right sided weakness and dysarthria on the background of one week history of right sided sciatica and malaise. He was apparently immunocompetent with only past medical history being hypertension. There was no consumption of tobacco or excess alcohol and he previously had normal liver and renal function.

Amelogenesis is the process of enamel formation. For amelogenesis to proceed, the cells of the inner enamel epithelium (IEE) must first proliferate and then differentiate into the enamel-producing ameloblasts. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective or absent tooth enamel. We identified a 2 bp variant c.817_818GC>AA in SP6, the gene encoding the SP6 transcription factor, in a Caucasian family with autosomal dominant hypoplastic AI. The resulting missense protein change, p.(Ala273Lys), is predicted to alter a DNA-binding residue in the first of three zinc fingers. SP6 has been shown to be crucial to both proliferation of the IEE and to its differentiation into ameloblasts. SP6 has also been implicated as an AI candidate gene through its study in rodent models. We investigated the effect of the missense variant in SP6 (p.(Ala273Lys)) using surface plasmon resonance protein-DNA binding studies. We identified a potential SP6 binding motif in the AMBN proximal promoter sequence and showed that wild-type (WT) SP6 binds more strongly to it than the mutant protein. We hypothesize that SP6 variants may be a very rare cause of AI due to the critical roles of SP6 in development and that the relatively mild effect of the missense variant identified in this study is sufficient to affect amelogenesis causing AI, but not so severe as to be incompatible with life. We suggest that current AI cohorts, both with autosomal recessive and dominant disease, be screened for SP6 variants.

Objectives: Visual-spatial neglect is a common attentional disorder after right-hemisphere stroke and is associated with poor rehabilitation outcomes. The presence of neglect symptoms has been reported to vary across personal, peripersonal, and extrapersonal space. Currently, no measure is available to assess neglect severity equally across these spatial regions and may be missing subsets of symptoms or patients with neglect entirely. We sought to provide initial construct validity for a novel assessment tool that measures neglect symptoms equally for these spatial regions: the Halifax Visual Scanning Test (HVST). Methods: In Study I, the HVST was compared to conventional measures of neglect and functional outcome scores (wheelchair navigation) in 15 stroke inpatients and 14 healthy controls. In Study II, 19 additional controls were combined with the control data from Study I to establish cutoffs for impairment. Patterns of neglect in the stroke group were examined. Results: In Study I, performance on all HVST subtests were correlated with the majority of conventional subtests and wheelchair navigation outcomes. In Study II, neglect-related deficits in visual scanning showed dissociations across spatial regions. Four inpatients exhibited symptoms of neglect on the HVST that were not detected on conventional measures, one of which showed symptoms in personal and extrapersonal space exclusively. Conclusions: The HVST appears a useful measure of neglect symptoms in different spatial regions that may not be detected with conventional measures and that correlates with functional wheelchair performance. Preliminary control data are presented and further research to add to this normative database appears warranted. (JINS, 2019, 25, 490–500)

ObjectiveTo determine whether anxiety and depression are associated with cognition in multiple sclerosis (MS), and whether these associations are similar in other immune-mediated inflammatory diseases (IMID; including inflammatory bowel disease [IBD] and rheumatoid arthritis [RA]) and in anxious/depressed individuals (ANX/DEP) without an IMID.MethodsParticipants (MS: n = 255; IBD: n = 247; RA: n = 154; ANX/DEP: n = 308) completed a structured psychiatric interview, the Hospital Anxiety and Depression Scale, and cognitive testing, including the Symbol Digit Modalities Test, the California Verbal Learning Test, and Letter Number Sequencing test. Test scores were converted to age-, sex-, and education-adjusted z scores. We evaluated associations of anxiety and depression with the cognitive z scores using multivariate linear models, adjusting for disease cohort.ResultsAll cohorts exhibited higher rates of impairment (i.e., z less than or equal to −1.5) in the domains of processing speed, verbal learning, and delayed recall memory relative to general population norms. Higher levels of anxiety symptoms were associated with slower processing speed, lower verbal learning, and lower working memory performance (all p < 0.001); higher levels of depression symptoms were associated with slower processing speed. These associations did not differ across cohorts.ConclusionAnxiety and depression are associated with lower cognitive function in MS, with a similar pattern observed in persons with other IMID, including IBD and RA, and persons without an IMID. Managing symptoms of anxiety and of depression in MS, as well as other IMIDs, is important to mitigate their effect on cognition.

Objectives: Variants in DLX3 cause tricho‐dento‐osseous syndrome (TDO, MIM #190320), a systemic condition with hair, nail and bony changes, taurodontism and amelogenesis imperfecta (AI), inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, six different DLX3 variants have been reported in TDO. The aim of this paper was to explore and discuss three recently uncovered new variants in DLX3. Subjects and Methods: Whole‐exome sequencing identified a new DLX3 variant in one family, recruited as part of an ongoing study of genetic variants associated with AI. Targeted clinical exome sequencing of two further families revealed another new variant of DLX3 and complete heterozygous deletion of DLX3. For all three families, the phenotypes were shown to consist of AI and taurodontism, together with other attenuated features of TDO. Results: c.574delG p.(E192Rfs*66), c.476G>T (p.R159L) and a heterozygous deletion of the entire DLX3 coding region were identified in our families. Conclusion: These previously unreported variants add to the growing literature surrounding AI, allowing for more accurate genetic testing and better understanding of the associated clinical consequences.

Smoking is a significant risk factor for morbidity and mortality, particularly among patients with tuberculosis (TB). Although smoking cessation is recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, there has been no published evaluation of smoking cessation interventions among people with TB. The purpose of this review was to synthesize the evidence on interventions and suggest practice, research and policy implications. A systematic review of the literature identified 14 peer-reviewed studies describing 13 smoking cessation interventions between 2007 and 2017. There were five randomized controlled trials, three non-randomized interventions, and five prospective cohort studies. The primary types of interventions were brief advice (Le tabac constitue un facteur de risque significatif en termes de morbidité et de mortalité, particulièrement pour les patients atteints de tuberculose (TB). L'arrêt du tabac a été recommandé par l'Organisation Mondiale de la Santé et l'Union Internationale contre la Tuberculose et les Maladies Respiratoires ; aucune évaluation n'a cependant été publiée à propos des interventions de sevrage du tabac parmi les personnes atteintes de TB. Le but de cette revue a été de synthétiser les données probantes relatives à ces interventions et de suggérer les implications en matière de pratique, de recherche et de politique. Une revue systématique de la littérature a identifié 14 études revues par des pairs, décrivant 13 interventions d'arrêt du tabac entre 2007 et 2017 : 5 essais randomisés contrôlés, 3 interventions non randomisées et 5 études prospectives de cohorte. Les types principaux d'intervention ont consisté en brefs conseils (El tabaquismo representa un importante factor de riesgo de morbilidad y mortalidad, sobre todo para los pacientes con tuberculosis (TB). La Organización Mundial de la Salud y la Unión Internacional contra la Tuberculosis y las Enfermedades Respiratorias han recomendado que se promueva la deshabituación tabáquica, pero aún no se ha publicado una evaluación de las intervenciones que favorecen el abandono del tabaquismo en las personas con diagnóstico de TB. La finalidad de la presente revisión consistió en reunir la evidencia existente sobre estas intervenciones y proponer los corolarios que se podrían aplicar en la práctica, la investigación y la formulación de políticas. En una revisión sistemática de artículos científicos se encontraron 14 estudios publicados del 2007 al 2017 en revistas con comité de lectura que describían 13 intervenciones de deshabituación tabáquica. Los artículos abordaban 5 ensayos aleatorizados, 3 intervenciones no aleatorizadas y 5 estudios de cohortes prospectivos. Los principales tipos de intervenciones consistieron en asesoramiento breve (

Background Variants in DLX3 cause tricho-dento-osseous syndrome (TDO; MIM accession no. 190320), a systemic condition with hair, nail, and bony changes, taurodontism, and amelogenesis imperfecta (AI) inherited in an autosomal dominant fashion. Different variants found within this gene are associated with different phenotypic presentations. To date, 6 different DLX3 variants have been reported in TDO. The aim of this paper is to explore and discuss 3 recently uncovered new variants in DLX3 and their resulting phenotypes. Objective To identify new variants associated with AI to increase the accuracy of genetic testing and elucidate the roles and functions of genes involved in amelogenesis. In this study, 3 new variants within DLX3 were identified as being associated with AI. Methods Whole-exome sequencing identified a new DLX3 variant in one family recruited as part of an ongoing study of genetic variants associated with AI. Targeted clinical exome sequencing of 2 further families revealed another new variant of DLX3 and a complete heterozygous deletion of DLX3. For all 3 families, the phenotypes consisted of AI and taurodontism, together with other attenuated features of TDO. Conclusions c.574delG p.(E192Rfs*66), c.476G>T (p.R159L), and a heterozygous deletion of the entire DLX3 coding region were identified in the families studied. These previously unreported variants add to the growing literature surrounding AI, allowing more accurate genetic testing and better understanding of the associated clinical consequences.

Background: Although family history is well established to be a risk factor for developing colorectal cancer (CRC), much less is known about its impact on patient survival. This study aimed to link CRC patient data from the National Study of Colorectal Cancer Genetics (NSCCG) to the National Cancer Data Repository (NCDR) to examine the relationship between family history and the characteristics and outcomes of CRC. Methods: All eligible NSCCG patients underwent a matching process to the NCDR using combinations of their personal identifiers. The characteristics and survival of CRC patients with and without a family history of CRC were compared. Results: Of the 10 937 NSCCG patients eligible to be matched into the NCDR, 10 782 (98.6%) could be fully linked. There were no significant differences between those with and without a family history of CRC (defined as having at least one affected first-degree relative) in terms of age, sex, tumour stage at diagnosis, presence of multiple cancers, mode of presentation to hospital and surgical management, although patients with familial CRC were more likely to have right-sided tumours (P

Background: Colorectal cancer is common in England and, with long-term survival relatively poor, improving outcomes is a priority. A major initiative to reduce mortality from the disease has been the introduction of the National Health Service (NHS) Bowel Cancer Screening Programme (BCSP). Combining data from the BCSP with that in the National Cancer Data Repository (NCDR) allows all tumours diagnosed in England to be categorised according to their involvement with the BCSP. This study sought to quantify the characteristics of the tumours diagnosed within and outside the BCSP and investigate its impact on outcomes. Methods: Linkage of the NCDR and BCSP data allowed all tumours diagnosed between July 2006 and December 2008 to be categorised into four groups; screen-detected tumours, screening-interval tumours, tumours diagnosed in non-participating invitees and tumours diagnosed in those never invited to participate. The characteristics, management and outcome of tumours in each category were compared. Results: In all, 76 943 individuals were diagnosed with their first primary colorectal cancer during the study period. Of these 2213 (2.9%) were screen-detected, 623 (0.8%) were screening-interval cancers, 1760 (2.3%) were diagnosed in individuals in non-participating invitees and 72 437 (94.1%) were diagnosed in individuals not invited to participate in the programme due to its ongoing roll-out over the time period studied. Screen-detected tumours were identified at earlier Dukes' stages, were more likely to be managed with curative intent and had significantly better outcomes than tumours in other categories. Conclusion: Screen-detected cancers had a significantly better prognosis than other tumours and this would suggest that the BCSP should reduce mortality from colorectal cancer in England.

This paper investigates a meta-heuristic solution approach to the early/tardy single machine scheduling problem with common due date and sequence-dependent setup times. The objective of this problem is to minimise the total amount of earliness and tardiness of jobs that are assigned to a single machine. The popularity of just-in-time (JIT) and lean manufacturing scheduling approaches makes the minimisation of earliness and tardiness important and relevant. In this research the early/tardy problem is solved by Meta-RaPS (meta-heuristic for randomised priority search). Meta-RaPS is an iterative meta-heuristic which is a generic, high level strategy used to modify greedy algorithms based on the insertion of a random element. In this case a greedy heuristic, the shortest adjusted processing time, is modified by Meta-RaPS and the good solutions are improved by a local search algorithm. A comparison with the existing ETP solution procedures using well-known test problems shows Meta-RaPS produces better solution...

Mercury amalgamation is the predominant gold processing method used in North Sulawesi and elsewhere in Indonesia. Only a portion of the mercury used in the process is recovered because floured mercury is discharged directly to upland disposal sites and streams with the tailings and Hg vapor are released when amalgam is heated without retorts to recover gold from amalgam. Cyanide (CN) processing was introduced to recover gold from the tailings so additional Hg vapor is released as the loaded charcoal is burned, breaking the Hg- CN complexes. Small scale gold mines in North Sulawesi alone emit approximately 64 tons of Hg per year to the environment, exceeding the 40 tons per year emitted from coal-fired power plants in the United States. Replacing Hg-amalgamation with gravity separation followed by vat cyanidation would bring about significant environmental benefits. In this paper we examine some of the more prevalent gold recovery practices in Indonesia, and propose management and beneficiation improvements. We believe these changes would yield higher recovery rates, and would eliminate the environmental damage caused by mercury losses that follow the current processes.

Shallow ponds associated with peatlands in boreal Alberta contain large quantities of stored carbon in their peaty sediments, and exhibit spatial changes in response to dry or wet conditions. Peatland ponds around Utikuma Lake experienced a partial to nearly complete drawdown in 2002, in response to drought. A fourfold investigation was begun to assess the natural drought and flood cycles, assess the current C stocks along the shore, determine what species were colonizing the newly exposed shorelines, and to place the magnitude of the current drought into historical perspective. Ten vegetation communities were found to have colonized the exposed sediments. Paleostratigraphy shows that the surface communities differ markedly from paleocommunities. Stratigraphy of the wetland sediments demonstrates that only two changes occurred, one a successional switch from a sedge-dominated marsh to a forested bog, the other a much more recent disturbance that caused water levels near the pond to rise. No evidence of constantly changing paleocommunities was found, suggesting that previous droughts have not left a visible paleorecord. The more recent disturbance has likely redistributed peat into the pond basins and subsequently it has broken down to detritial peat, altering its physical structure, and perhaps its rate of decomposition. Continued exposure of the peat is likely to enhance decomposition. In this study both flooding and drought may have impacted the wetland in ways likely to result in higher rates of decomposition and enhanced CO2 emissions under global warming. Key words: Peat stratigraphy, Holocene climate, thermokarst melting, detrital peat, carbon stocks

Peatland plant communities surrounding small (

This paper investigates the development and application of a general meta-heuristic, Meta-RaPS (meta-heuristic for randomized priority search), to the traveling salesman problem (TSP). The Meta-RaPS approach is tested on several established test sets. The Meta-RaPS approach outperformed most other solution methodologies in terms of percent difference from optimal. Additionally, an industry case study that incorporates Meta-RaPS TSP in a large truck route assignment model is presented. The company estimates a more than 50% reduction in engineering time and over $2.5 million annual savings in transportation costs using the automated Meta-RaPS TSP tool compared to their current method.

Indonesia's fire and haze problem is increasingly being ascribed to large-scale forest conversion and land clearing activities making way for pulpwood, rubber and oil palm plantations. Fire is the cheapest tool available to small holders and plantation owners to reduce vegetation cover and prepare and fertilize extremely poor soils. Fires that escaped from agricultural burns have ravaged East Kalimantan forests on the island of Borneo during extreme drought periods in 1982–1983, 1987, 1991, 1994 and 1997–1998. Estimates based on satellite data and ground observations are that more than five million hectares were burned in East Kalimantan during the 1997/1998 dry season. Not only were the economic losses and ecological damage from these surface fires enormous, they ignited coal seams exposed at the ground surface along their outcrops. Coal fires now threaten Indonesia's shrinking ecological resources in Kutai National Park and Sungai Wain Nature Reserve. Sungai Wain has one of the last areas of unburned primary rainforest in the Balikpapan–Samarinda area with an extremely rich biodiversity. Although fires in 1997/1998 damaged nearly 50% of this Reserve and ignited 76 coal fires, it remains the most valuable water catchment area in the region and it has been used as a reintroduction site for the endangered orangutan. The Office of Surface Mining provided Indonesia with the capability to take quick action on coal fires that presented threats to public health and safety, infrastructure or the environment. The US Department of State's Southeast Asia Environmental Protection Initiative through the US Agency for International Development funded the project. Technical assistance and training transferred skills in coal fire management through the Ministry of Energy and Mineral Resource's Training Agency to the regional offices; giving the regions the long-term capability to manage coal fires. Funding was also included to extinguish coal fires as demonstrations to the Indonesian Government. Successful demonstrations obtained visible benefits for a large number of local interests and received overwhelmingly favorable public response. This built the public and political support needed to continue this work. These successes encouraged the Ministry to officially assume the responsibility for coal fire management by Decree 1539/20/MPE/1999. The Ministry reallocated internal funds to support portions of the immediate suppression projects and committed a portion of the Coal Royalty Fund to provide long-term support for coal fire suppression activities. Coal fires continue to present a serious risk to Indonesia's ecosystems, population and forest resources. The Ministry and local governments in East Kalimantan are still working on the coal fire inventory. It presently contains 164 coal fires, but it is far from complete. Unless these coal fires are managed or extinguished, they will add to the already catastrophic cycle of anthropogenic forest fires that further reduce Indonesia's forest resources and endangered species while contributing unnecessarily to global carbon emissions.

Many Brooks algorithm (BAG)-based heuristics have been proposed to solve the constrained multiple resource problem. BAG starts at the beginning of a project network, determines a list of available tasks, and then uses a heuristic to select a task to schedule. This research modifies BAG to solve the project network in both a forward and backward (F&B) direction. This modified BAG approach was used on Patterson's 110 test problems with several selection heuristics, such as ACTIM, latest finish time (LFT), resource over time (ROT), and ACTRES. Results of this research show that solving the networks in both the F&B directions led to improvements of more than 30% for the average error, the maximum error and the percentage of optimum solutions found when compared to the traditional BAG approach.

This paper investigates the development and application of a simple heuristic to the resource constrained project scheduling problem (RCPSP). This computer heuristic, which is based on the COMSOAL heuristic, constructs a feasible solution at each iteration and chooses the best solution of several iterations. Although COMSOAL was originally a solution approach for the assembly-line balancing problem, it can be extended to provide solutions to the resource allocation problem. The Modified COMSOAL technique presented in this paper uses priority schemes intermittently with a random selection technique. This hybrid of randomness and priority scheme allows a good solution to be found quickly while not being forced into the same solution at each iteration. Several different priority schemes are examined within this research. The COMSOAL heuristic modified with the priority schemes heuristic was tested on several established test sets and the solution values are compared with both known optimal values and the res...

Generating a project schedule that meets all activity precedence constraints while minimizing the overall project duration is often difficult. The complex project-scheduling problem is further complicated by the real-world constraint that often a limited number of resources must be allocated to competing activities. This paper investigates the application of the computer method COMSOAL to this resource allocation problem. COMSOAL (Computer Method of Sequencing Operations for Assembly Lines), originally a solution approach for the assembly line balancing problem, is a computer heuristic that can be used to generate a feasible solution to the resource allocation problem at each iteration of the heuristic. A solution methodology of repeatedly running COMSOAL will result in many feasible solutions from which the best is chosen. This solution approach now becomes viable given the increased speed of inexpensive computers. This paper discusses the adaptation of the COMSOAL approach to the resource allocation problem as well as a designed experiment used to investigate the appropriateness of COMSOAL for a known set of resource allocation test problems. Results from this experiment show COMSOAL is a viable method to solve these resource allocation problems when compared to the results from several well-known resource allocation algorithms and to the optimal solutions.

Pig skin was used as a model to study the effectiveness of two topically applied creams, Lipochromin and Levosinum, in modifying the development of both early and late radiation damage to pig skin. Irradiated skin sites that received daily topical application of Levosinum or Lipochromin after exposure were compared with sites on the contralateral flank of the same animal that received irradiation only. Irradiation was with graded doses of 90Sr/90Y beta-rays. Incidence of moist desquamation (acute) and ischaemic dermal necrosis (late) were used as end-points. The latency period for the development of moist desquamation and its healing time was also assessed. The latency period for the development of moist desquamation in this model ranged from 4.00-6.75 weeks. There was no significant difference between the cream treatment and control sites. Application of Levosinum shortened the healing time of moist desquamation at each dose level by 5-10 days. In three out of four dose levels used, this shortening of the healing time was statistically significant (p0.03). Treatment with these topical applications also reduced the incidence of late dermal necrosis and increased the ED50 values for the incidence of dermal necrosis. This increase in ED50 values was equivalent to a dose modification factor of 1.11-1.13.

Normal tissue radiation injury occurs after sufficient irradiation, thus limiting the curative potential of x-ray therapy. In the kidney, radiation injury results in fibrosis and, ultimately, renal failure. The mediators of fibrosis in radiation nephropathy have received scant attention. Therefore, we evaluated the sequential presence of alpha smooth muscle actin (alphasma), fibrin, collagen, and TGFbeta1 in a porcine model of radiation nephropathy using 9.8 Gy single-dose local kidney irradiation. During the 24-week study, there was progressive and significant collagen accumulation in glomeruli and in interstitium. In glomeruli, this was associated with significant mesangial alphasma expression by 2 weeks after irradiation, a further rise at 4 weeks, and then a gradual fall to baseline. Glomerular fibrin deposition was significant by 4 weeks after irradiation, and remained elevated thereafter. There was little or no glomerular TGFbeta1 expression at any time point. Tubular fibrin deposition was significant at 4 weeks after irradiation but declined thereafter. There was little or no tubulo-interstitial alphasma expression at any time after irradiation. At 6 weeks after irradiation, there was a significant peak of tubular epithelial TGFbeta1 expression that declined thereafter. The early glomerular injury is evident as mesangial alphasma expression but is not proceeded by TGFbeta1 expression. There is sustained glomerular fibrin deposition with deposition of fibrin in tubular lumens, suggesting that tubular fibrin derives and flows out from injured glomerular tufts. We conclude that i) alphasma expression is an early marker of glomerular radiation injury, presaging scarring; ii) fibrin deposition is involved in glomerular and tubular radiation injury; and iii) TGFbeta1 is not an early event in radiation nephropathy, and not apparent in glomeruli in this model, but may correlate with later tubulo-interstitial fibrosis. Thus, the mediators of scarring in this model differ according to time after injury and also according to the affected tissue compartment.

Fibrosis in chronic renal failure is closely associated with declining function. Its role in affecting function is less well defined. The radiation model of chronic renal failure was used to examine the tissue distribution of fibrosis and scarring and its role in influencing the loss of function in chronic renal disease. A striking and progressive pattern of fibrosis and narrowing of the glomerulotubular neck was found in irradiated pig kidneys. These narrowed necks increased in prevalence with time after irradiation. At 20 weeks after irradiation, the average neck diameter reduction was 60%, as compared with nonirradiated controls, a percentage that is consistent with a reduction in flow and pressure at this critical point of the nephron. Glomerulotubular neck narrowing may thus directly reduce the glomerular filtration rate of an individual nephron. Fibrotic neck stenoses may be a factor in progressive chronic renal failure.

Background Clinical guidelines recommend that, where clinically appropriate, laparoscopic tumour resections should be available for patients with colorectal cancer. This study aimed to examine the introduction of laparoscopic surgery in the English National Health Service. Methods Data were extracted from the National Cancer Data Repository on all patients who underwent major resection for a primary colorectal cancer diagnosed between 2006 and 2008. Laparoscopic procedures were identified from codes in the Hospital Episode Statistics and National Bowel Cancer Audit Project data in the resource. Trends in the use of laparoscopic surgery and its influence on outcomes were examined. Results Of 58 135 resections undertaken over the study period, 10 955 (18·8 per cent) were attempted laparoscopically. This increased from 10·0 (95 per cent confidence interval (c.i.) 8·1 to 12·0) per cent in 2006 to 28·4 (25·4 to 31·4) per cent in 2008. Laparoscopic surgery was used less in patients with advanced disease (modified Dukes' stage ‘D’ versus A: odds ratio (OR) 0·45, 95 per cent c.i. 0·40 to 0·50), rectal tumours (OR 0·71, 0·67 to 0·75), those with more co-morbidity (Charlson score 3 or more versus 0: OR 0·69, 0·58 to 0·82) or presenting as an emergency (OR 0·15, 0·13 to 0·17). A total of 1652 laparoscopic procedures (15·1 per cent) were converted to open surgery. Conversion was more likely in advanced disease (modified Dukes' stage ‘D’ versus A: OR 1·56, 1·20 to 2·03), rectal tumours (OR 1·29, 1·14 to 1·46) and emergencies (OR 2·06, 1·54 to 2·76). Length of hospital stay (OR 0·65, 0·64 to 0·66), 30-day postoperative mortality (OR 0·55, 0·48 to 0·64) and risk of death within 1 year (hazard ratio 0·60, 0·55 to 0·65) were reduced in the laparoscopic group. Conclusion Laparoscopic surgery was used more frequently in low-risk patients.

The ability of essential fatty acids (EFAs) to modulate radiation-induced normal tissue injury was assessed in pig skin. Female Large White pigs (approximately 25 Kg) received 3 ml/day orally of either an 'active' oil [So-1100, containing 9% gamma-linolenic acid (GLA)] or a 'placebo' oil (So-1129) for just 4 weeks before or for 4 weeks before and for 16 weeks after irradiation; localised irradiation of skin was with single doses of beta-rays from 22.5 mm diameter 90Sr/90Y plaques. The severity of the acute reaction, assessed in terms of erythema or moist desquamation, was significantly less in those pigs that received So-1100 both before and after irradiation, as compared with those receiving that oil only prior to irradiation and the 'placebo' groups. Dose modification factors (DMFs) of between 1.13-1.24 were obtained. A similar reduction in the severity of acute skin injury was seen in pigs receiving So-1100 for only 10 weeks after irradiation. Late skin damage, assessed in terms of late erythema or dermal necrosis, was also reduced with So-1100, with DMFs of 1.14-1.51. No such modification was observed if So-1100 was only administered for 4 weeks prior to irradiation. No adverse side-effects were apparent as a result of EFA administration. So-1100 may represent a safe and valuable method of increasing the therapeutic gain in radiotherapy.

Low-level light from a multi-wavelength array of light sources has been used to prevent late X-ray-induced dermal necrosis in the pig. Skin fields, measuring 4 × 4 cm on the flank, were irradiated with a single dose of 23.4 Gy of X-rays. This X-ray dose was associated with the development of a 100% incidence of dermal necrosis, 10–16 weeks after irradiation. These irradiated skin sites were subsequently exposed to light of 660, 820, 880, and 950 nm wavelengths from a gallium aluminium arsenide multiple wavelength multidiode cluster probe (Biotherapy Medical Laser, 3ML), three times a week, from 4 to 16 weeks or 6 to 16 weeks after X-irradiation. The skin fields were exposed to the light pulsating at either 2.5 Hz or 5 kHz. With light pulsating at 5 kHz, energy densities of 0.22, 0.54, 1.08 2.16, 4.32, and 10.8 J/cm2 were used. Treatment with light pulsating at 2.5 Hz, 6–16 weeks after X-irradiation, or treatment with light pulsating at 5 kHz, 4–16 weeks after X-irradiation, did not have a significant effect on the incidence or the latency for the development of ischemia dermal necrosis irrespective of the exposure time to light at each treatment. With light pulsating at 5 kHz, no effect of light dose was observed. However, the overall incidence of dermal necrosis was significantly reduced (P = 0.001) to 52% in the X-irradiated fields receiving treatment with 5 kHz light, 6–16 weeks after X-irradiation. Treatment with light for only three days immediately after X-irradiation with 5 kHz light had no beneficial effect. These findings suggest that light when applied appropriately may be useful in the prevention of late X-ray-induced damage to the dermis provided that it is given for the most appropriate time after X-irradiation. © 1992 Wiley-Liss, Inc.

Mature Large White female pigs aged approx. 10 months received single intravenous doses of 1.5, 2, or 2.5 mg/kg cisplatin. The glomerular filtration rate (GFR) and the effective renal plasma flow (ERPF) in individual kidneys were measured prior to and at 4-week intervals for up to 24 weeks after cisplatin administration by renography using [99mTc]-diethylenetriamminepentaacetic acid (DTPA) and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated pig and that of three age-matched control pigs was then removed, and GFR and ERPF values were measured in the remaining kidney at 4-week intervals for a further 24 weeks after unilateral nephrectomy (UN). Pigs treated with cisplatin showed no significant reduction in GFR or ERPF for up to 24 weeks after drug infusion. As measured using inductively coupled plasma mass spectrometry, the mean renal platinum concentration in the left kidney removed at UN was 77.5 +/- 9.1 ng/g kidney per mg/kg cisplatin. Histological evaluation of these kidneys revealed narrow interconnecting rays of interstitial fibrosis in the deep cortex and medulla; in these areas, glomeruli exhibited thickened Bowman's capsules and occasionally shrunken sclerotic capillaries. In cisplatin-treated pigs, UN was associated with a marked reduction in the ability of the remaining kidney to increase its function in terms of GFR and, to a lesser extent, of ERPF. The increase seen in GFR following UN in the cisplatin-treated pigs was only ca. 50%-70% of that seen in age-matched UN controls. Histologically, these kidneys revealed resolution of the peritubular fibrosis observed at UN; occasional sclerotic glomeruli were also evident. Platinum remained detectable in these kidneys, the mean levels being 18.8 +/- 4.9 ng/g kidney per mg/kg cisplatin. These findings confirm previous observations and illustrate the need for caution in considering further treatment of patients who have previously received cisplatin along with a second potentially nephrotoxic agent.

The software-oriented, multi-processor database systems are characterized by a set of processing elements (PEs) which run identical software and operate on a partitioned database in parallel. Performance improvements and capacity growth can be achieved in this type of system by adding PEs to the configuration and replicating the existing software on the added PEs. Much work has been done applying graph theory, queuing theory, algorithmic approaches, and analytical techniques towards the design of multi-processor database systems. This paper describes a simulation approach and the application of a simulation language, SLAM, to the design and performance analysis of one such multi-processor database system. The system, relational replicated database system (RRDS), was developed using a five-phase design process. Simulation and analytical techniques were used throughout the development to determine critical elements, components, and design issues, and to evaluate proposed solutions. RRDS was modeled as an open queuing system with SLAM service times determined analytically. The model consisted of a workload scenario generator, a query processing module, and a statistics collection module. In phase one of the simulation study, different hardware organizations were evaluated. Results indicated that the RRDS approach performs approximately three times better than other approaches such as SIMD, MIMD, and functional specialization. In phase two, algorithms and mechanisms for data access were developed. Results favored the B + -tree approach over the clustering approach. A data placement strategy was determined in phase three. Results indicated that the value range partitioning (VRP) approach is more desirable than the round-robin (RR) approach. In phase four, a directory management strategy was selected. Results favored a partitioned and parallel-processed directory, as opposed to a rotating approach. Finally, phase five consisted reveal system strengths and weaknesses, and gain insight into optimal RRDS operating environments. This approach to database system design is both iterative and evolutionary, and can be applied regardless of the type of system being considered. Simulation can be a useful tool in all phases of database system design, from the actual physical hardware architecture to the resolution of software design questions. It plays an important role in predictive performance analysis to determine the extent to which original design goals are achieved.

Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to approximately 90, approximately 120 and approximately 150 mg/m2) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [99 mTc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically, and GFR and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with greater than or equal to 2 mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S1 portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GFR and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was less than 50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically "silent" until exposure to an additional nephrotoxic insult.