The renal clear cell carcinoma immune landscape.

A comprehensive evaluation of the clear cell renal cell carcinoma (ccRCC) immune landscape was found using 584 RNA-sequencing datasets from The Cancer Genome Atlas (TCGA), we identified 17 key dysregulated immune-associated genes in ccRCC based on association with clinical variables and important immune pathways. Of the numerous findings from our analyses, we found that several of the 17 key dysregulated genes are heavily involved in interleukin and NF-kB signaling and that somatic copy number alteration (SCNA) hotspots may be causally associated with gene dysregulation. More importantly, we also found that key immune-associated genes and pathways are strongly upregulated in ccRCC. Our study may lend novel insights into the clinical implications of immune dysregulation in ccRCC and suggests potential immunotherapeutic targets for further evaluation.

Detection of daily clouds on Titan.

We have discovered frequent variations in the near-infrared spectrum of Titan, Saturn's largest moon, which are indicative of the daily presence of sparse clouds covering less than 1% of the area of the satellite. The thermodynamics of Titan's atmosphere and the clouds' altitudes suggest that convection governs their evolutions. Their short lives point to the presence of rain. We propose that Titan's atmosphere resembles Earth's, with clouds, rain, and an active weather cycle, driven by latent heat release from the primary condensible species.

The dusty atmosphere of the brown dwarf Gliese 229B.

The brown dwarf Gliese 229B has an observable atmosphere too warm to contain ice clouds like those on Jupiter and too cool to contain silicate clouds like those on low-mass stars. These unique conditions permit visibility to higher pressures than possible in cool stars or planets. Gliese 229B's 0.85- to 1.0-micrometer spectrum indicates particulates deep in the atmosphere (10 to 50 bars) having optical properties of neither ice nor silicates. Their reddish color suggests an organic composition characteristic of aerosols in planetary stratospheres. The particles' mass fraction (10(-7)) agrees with a photochemical origin caused by incident radiation from the primary star and suggests the occurrence of processes native to planetary stratospheres.

Collision of comet Shoemaker-Levy 9 with Jupiter observed by the NASA infrared telescope facility.

The National Aeronautics and Space Administration (NASA) Infrared Telescope Facility was used to investigate the collision of comet Shoemaker-Levy 9 with Jupiter from 12 July to 7 August 1994. Strong thermal infrared emission lasting several minutes was observed after the impacts of fragments C, G, and R. All impacts warmed the stratosphere and some the troposphere up to several degrees. The abundance of stratospheric ammonia increased by more than 50 times. Impact-related particles extended up to a level where the atmospheric pressure measured several millibars. The north polar near-infrared aurora brightened by nearly a factor of 5 a week after the impacts.

A modified ATP benchmark for evaluating the cleaning of some hospital environmental surfaces.

Hospital cleaning continues to attract patient, media and political attention. In the UK it is still primarily assessed via visual inspection, which can be misleading. Calls have therefore been made for a more objective approach to assessing surface cleanliness. To improve the management of hospital cleaning the use of adenosine triphosphate (ATP) in combination with microbiological analysis has been proposed, with a general ATP benchmark value of 500 relative light units (RLU) for one combination of test and equipment. In this study, the same test combination was used to assess cleaning effectiveness in a 1300-bed teaching hospital after routine and modified cleaning protocols. Based upon the ATP results a revised stricter pass/fail benchmark of 250 RLU is proposed for the range of surfaces used in this study. This was routinely achieved using modified best practice cleaning procedures which also gave reduced surface counts with, for example, aerobic colony counts reduced from >100 to <2.5 cfu/cm(2), and counts of Staphylococcus aureus reduced from up to 2.5 to <1 cfu/cm(2) (95% of the time). Benchmarking is linked to incremental quality improvements and both the original suggestion of 500 RLU and the revised figure of 250 RLU can be used by hospitals as part of this process. They can also be used in the assessment of novel cleaning methods, such as steam cleaning and microfibre cloths, which have potential use in the National Health Service.

Successful AV fistula creation does not lead to higher catheter use: the experience by the Northwest Renal Network 16 Vascular Access Quality Improvement Program. Four years follow-up.

BACKGROUND: In 2002, the Center for Medicare and Medicaid Services (CMS) required all 18 Renal Networks to participate in a Vascular Access Quality Improvement Program (QIP). The Northwest Renal Network (NWRN 16) chose to increase arteriovenous fistula (AVF) use. NWRN 16 hypothesized that strategies which targeted the improvement of AVF rate and the reduction of catheter use were the same. In December 2001, 44.2% of hemodialysis (HD) patients in the NWRN 16 received HD using an AVF which met the Dialysis Outcome Quality Initiative (K/DOQI) 40% AVF guideline for prevalent patients. However, 43% of HD facilities (2869 patients) had less than 40% of AVF and higher HD catheter rates than the average Network catheter rates (25.0 vs. 20.3%). To address the needs of underperforming facilities, NWRN 16 provided education and tools for their vascular access decision makers to promote AVF creation and catheter reduction. METHODS: In 2002, NWRN 16 sponsored four regional workshops targeted at nephrologists, vascular surgeons, HD nurses, and interventional radiologists. RESULTS: Percentage of AVFs in use in invited facilities increased from 31.3% pre-intervention to 56.2% at 4 yrs: 78% increase (99% confidence interval: 77.8% to 81.5%). Percentage of catheters increased from 25% to 25.8%: 3.2% change over 4 yrs (99% confidence interval: 2.5% to 4%). CONCLUSION: The success of Network 16's AVF interventions demonstrates the effectiveness of Network education promoting multidisciplinary teamwork, and innovative strategies to increase dramatically AVF use without substantial increase in catheter use.

An evaluation of different methods for the recovery of meticillin-resistant Staphylococcus aureus from environmental surfaces.

Although the association between environmental surfaces contaminated with meticillin-resistant Staphylococcus aureus (MRSA) and hospital infection rates is not fully understood, monitoring programmes can provide an objective starting point for the development and assessment of infection control strategies incorporating improved cleaning. There is, however, no universally accepted method for the recovery of MRSA from environmental surfaces, and the aim of this study was to evaluate a selection of currently available methods. Using five clinical isolates of MRSA and seven protocols, known numbers of bacteria were inoculated on to a stainless steel surface and either recovered immediately (without drying or adsorption) or recovered after 30min (with drying at room temperature and adsorption of cells to the surface). Surfaces were either swabbed or sampled directly by contact methods, and four nutritive media (blood, tryptone soya, oxacillin and meticillin-resistant agars) were tested. Relative sampling efficiencies were determined and the sensitivity of each method per 100cm(2) was calculated. Wide variation in the ability to recover MRSA was found between the different protocols. In the recovery of dried (adsorbed) cells, direct contact methods demonstrated higher sampling efficiency than swabs. The sensitivity of all methods was lower in recovering adsorbed cells from surfaces than unadsorbed cells. Sampling methods consistently proved to be more important than the choice of medium. Dipslides coated with selective agar are recommended for recovering MRSA from flat environmental surfaces.

The effectiveness of existing and modified cleaning regimens in a Welsh hospital.

Hospital cleaning currently has a high media profile. The effectiveness of an existing ward-cleaning regimen was assessed at selected sites over a 14 day period and shown to be highly variable. The cleaning regimen was subsequently modified in two stages, both changes involving a rinse stage and substituting cloths with disposable paper towels. One modification continued using the existing detergent; the other replaced detergent with a quaternary ammonium sanitiser. Both modifications yielded significantly lower and more consistent bacterial counts. Assessment of residual organic soil using adenosine triphosphate (ATP) detection demonstrated that failure rates (measurements exceeding benchmark clean value of 500 relative light units (RLU)) fell from 86-100% after existing cleaning methods, to 0-14% after modified cleaning. Maximum ATP readings fell from 163,870 to 2289 RLU. Incorporating a quaternary ammonium sanitiser into the cleaning regimen produced a further slight, but not significant, improvement in cleaning efficacy. These findings suggest that simple improvements can be made to existing cleaning regimens to increase their efficacy.

Creation of secondary AV fistulas from failed hemodialysis grafts: the role of routine vein mapping.

Pre-existing forearm grafts lead to dilatation of upper arm veins of the ipsilateral arm that greatly facilitates the creation of secondary arteriovenous fistulas (AVF). In this retrospective review of 18 patients, the routine and periodical revision of failed grafts were discontinued. Vein mapping by physical examination or Duplex studies was performed prior to graft failure and a secondary AVF was created when the graft failed. Using this management strategy, an AVF creation success rate of 95% was achieved despite high incidence of co-morbidity factors within the patient population. This success rate demonstrates the value of vein selection by vascular mapping prior to graft failure and early vascular access planning in the successful creation of secondary AVF.

Successful multidisciplinary interventions for arterio-venous fistula creation by the Pacific Northwest Renal Network 16 vascular access quality improvement program.

BACKGROUND: In December 2001, 44.2% of hemodialysis (HD) patients in the Northwest Renal Network (NWRN 16) received dialysis using an arteriovenous fistula (AVF). Substantial differences were noted in percentages of patients with AVF, ranging from 5% to 90% of the facility population, suggesting wide variation in physician practice patterns within the Network. To address the needs of facilities having < 40% AVF, NWRN 16 provided education and tools for their vascular access decision-makers to promote AVF creation. METHODS: In 2002, the Network sponsored 4 regional workshops targeted to nephrologists, vascular surgeons, dialysis nurses, and interventional radiologists. RESULTS: 46 facilities (43% of all Network facilities) had <40% AVF in use in December, 2001, dialyzing 2940 patients (Invited Units). Percent AVF in use in all the Invited Facilities increased from 31.3% pre-intervention to 39.8% at 1 year (p<0.001 vs pre) to 56.2% at four years: 79.8% increase in the prevalent AVF rate over a four-year period (95% confidence interval: 77.8% to 81.7%). CONCLUSION: Low prevalent AVF rates in many NWRN 16 facilities may have resulted from differences in physician practice patterns. The success of Network 16 AVF Intervention demonstrates the effectiveness of Network education promoting multidisciplinary teamwork, innovative strategies to increase AVF rates among dialysis patients.

Potential for improving fiber digestion in the rumen of cattle (Bos taurus) through microbial inoculation from bison (Bison bison): In situ fiber degradation.

The objective of this experiment was to determine if partial replacement of cattle rumen contents with those from bison would increase in situ ruminal fiber degradation of various forages. The second objective was to examine individual variation among cattle in their ability to degrade forage and their responses to inoculation. In situ degradation of barley straw, canola straw, alfalfa hay, and timothy hay was measured in 16 ruminally cannulated heifers fed a barley straw-based diet before and after inoculation with combined rumen contents from 32 bison (performed twice, 14 d apart). Each feed was incubated in the rumen of each heifer for 0, 4, 8, 12, 24, 48, 96, and 120 h, and the degradation parameters were determined as washout fraction (), potentially degradable fraction (), rate of digestion of fraction (), and total potentially degradable fraction (). The of barley straw decreased ( = 0.04) after inoculation, whereas fraction of NDF increased ( = 0.03) and fraction of NDF and ADF decreased ( ≤ 0.02) by inoculation. In contrast, of alfalfa hay NDF and ADF decreased ( = 0.002) after inoculation, but fraction of NDF and ADF ( ≤ 0.02) increased. There were no major effects ( > 0.06) of inoculation on the fiber degradation of timothy hay or canola straw. The differential response between barley straw and alfalfa hay may have occurred because the cattle were previously adapted to a barley straw diet, whereas the bison were fed barley silage and oats. Some animals consistently ranked higher or lower for or across at least 3 of the 4 feeds incubated, but the rankings changed after inoculation. In conclusion, inoculation of cattle with bison rumen contents failed to improve degradation of fiber from barley straw, canola straw, or timothy hay in cattle well adapted to a barley straw diet, although there were small improvements in the extent of degradation of fiber from alfalfa hay. Cattle varied both in their ability to degrade various forages and in their responses to inoculation with bison rumen contents.

A laboratory evaluation of the decontamination properties of microfibre cloths.

Standards of cleanliness in health care continue to attract attention. Effective cleaning requires the input of energy, and microfibre cloths may help in the physical removal of soil. The ability of these cloths to remove organic soil (measured by ATP) and bacteria was compared with paper towel and a conventional cloth in controlled wet and dry conditions. When used wet on a dry surface, the cleaning ability of six different microfibre cloths was variable, and in most cases, not significantly better than paper towel or a conventional cloth. One type of microfibre cloth did perform significantly better than the others and paper towel in reducing both organic soil and microbial load. When used dry on a dry surface, there was no significant difference between the cloths, and none of the cloths reduced microbial and organic bioburden effectively. The ability of the cloths to recontaminate the surface was also tested, and some of the microfibre cloths transferred significantly less organic debris and micro-organisms back to the surface than other cloths. Different makes of microfibre cloths have different characteristics, and the name 'microfibre' should not imply superior cleaning efficacy.

Breast cancer multi-disciplinary teams in England: much achieved but still more to be done.

OBJECTIVE: To look at the national coverage, composition and discussion of breast cancer multi-disciplinary teams (MDTs) in England. DESIGN AND DATA SOURCE: All breast units in England both symptomatic and screening were sent a questionnaire. MAIN OUTCOME MEASURES: Attendance of core members at MDT meetings; Percentage of patients discussed with a treatment plan; Private patients discussed; Reconstructive surgery. RESULTS: The majority of core members of the breast MDT attend weekly meetings to discuss the multidisciplinary management of patients with breast cancer, although attendance by medical oncologists and reconstructive breast surgeons is limited. Three MDTs never had a radiologist present and 3 never had a pathologist present at the MDT meeting. Most breast MDTs have a meeting coordinator to collect case-notes, radiographs and pathology reports to facilitate the meeting. Seventy-nine out of 134 teams discuss every cancer patient and 118 also discuss private patients. Twenty-seven teams record the outcome of the MDT meeting electronically, 32 teams book surgery, 16 radiotherapy and 15 book chemotherapy direct from the MDT meeting.

All radial scars/complex sclerosing lesions seen on breast screening mammograms should be excised.

AIM: To determine the incidence of pre-malignant and malignant conditions in radial scars identified from screening mammograms in women taking part in the UK NHS breast cancer screening programme. METHODS: All women in our screening population from 1988 to 2002 with a radiological diagnosis of radial scar or complex sclerosing lesion confirmed on subsequent histopathology were included in this study. Patients were investigated with fine needle aspiration cytology then localisation biopsy (n=46) or straight to localisation biopsy (n=78). Patients where divided into two groups, one with pure RS/CSL with no associated epithelial features and the second with associated ADH, DCIS or invasive cancer. RESULTS: One hundred and twenty-four lesions were confirmed histologically as radial scar or complex sclerosing lesions. The median age was 58 years. Of the 124 patients, 82 were pure RS/CSL. Forty-two had associated epithelial lesions, 22 patients had ADH and 20 patients had either in situ or invasive carcinoma. Where FNA was performed (n=46), mammograms had shown three lesions suspicious of cancer, which were not proven histologically. Mammograms picked up five malignancies out of the nine RS/CSL with associated cancers. Of these, FNA confirmed malignancy in only two patients. Where FNA was not done (n=78), mammogram had read five pure RS/CSL as cancers. It picked up only four cancers in RS lesions with DCIS/Ca out of 11. CONCLUSION: All screen-detected stellate lesions should be excised due to their association with pre-malignant and malignant conditions.

Bupropion: clinical assay for amphetamine-like abuse potential.

Bupropion hydrochloride (100, 200, and 400 mg), d-amphetamine sulfate (15 and 30 mg), and placebo were compared in 13 volunteers who had histories of amphetamine abuse. Each dose was given orally at intervals of 3 or more days according to a double-blind, randomized crossover design. Bupropion had little or no effect on blood pressure, pulse rate, respiration, body temperature, pupil diameter, subjective appetite, food intake, sleep, or selected subscales of the Addiction Research Center Inventory and Single Dose Questionnaire. Conversely, d-amphetamine was active on most measures. It is concluded that, despite bupropion's reinforcing properties in animals, the compound is not amphetamine-like and is unlikely to give rise to such abuse in humans.

Human spleen cells mediating natural killing: altered natural cytotoxicity of spleen effector cells from patients with carcinoma.

Spleen cells from eight patients with abdominal carcinoma and six patients undergoing major surgery for a variety of disease entities were assayed for natural cytotoxicity towards 51Cr-labelled K 562 target cells. Patients with abdominal cancer were shown to have relatively weak splenic natural cytotoxicity compared with the reactivity of effector cells from non-carcinoma patients. Nylon wool non-adherent spleen effector cells from cancer patients showed reduced cytolytic capacity compared with effector cells prepared from the spleens of other patients or peripheral blood mononuclear cells (PBMC) obtained from healthy individuals, whereas the splenic reactivity of non-cancer patients showed the same nylon wool separation profile as PBMC, high cytolytic activity being associated with nylon wool non-adherent effector cells. Splenic effector cell cytotoxicity from cancer and non-cancer patients was enhanced following exposure to human interferon, and inhibited by treatment with cholera toxin and simple sugars. Furthermore, fractionation of spleen cells on Percoll discontinuous density gradients demonstrated natural cytotoxic activity to reside predominantly in the low density cell fractions, similar to that found with NK cells from peripheral blood. Thus the properties described here for human cytotoxic spleen cells are similar to those described for peripheral blood NK cells, suggesting these two effector cell populations to be closely related, if not identical.

The use of a standard proforma in breast cancer reporting.

AIM: To determine whether the introduction of a standard reporting proforma has led to an improvement in the completeness of histopathology reports for breast cancer excision specimens. METHODS: A standard reporting proforma was designed using the Royal College of Pathologists' minimum dataset for breast cancer histopathology reports and the national histopathology reporting form of the National Health Service (NHS) breast screening programme. This was introduced into our department in June 1999, with reports generated from the proforma replacing the standard text reports. The pathological information contained in 50 text reports issued before the introduction of the proforma and 50 reports generated using the proforma was compared with the minimum dataset and NHS breast screening programme guidelines. RESULTS: A general improvement in documentation of individual pathological features was noted after introduction of the proforma. This was most significant in relation to documentation of features, such as microcalcification and ductal carcinoma in situ. In addition, important features such as tumour grade, tumour size, and hormone receptor status were documented more frequently in the proforma group. There was an overall increase in the number of reports regarded as complete after introduction of the proforma. CONCLUSIONS: The introduction of a standard proforma led to a significant improvement in the completeness of breast cancer histopathology reports in this centre, but continued vigilance is needed to ensure that standards continue to improve.

Colostomy wound closure.

The management of the wound at the time of colostomy closure has been controversial, and wound infection is a frequently cited complication of this procedure. We have conducted a prospective randomized study of colostomy wound closure in 105 patients with three study groups: (1) primary closure (n = 38); (2) primary closure with subcutaneous drains (n = 29); and (3) delayed primary closure (n = 38). All patients had mechanical bowel preparation with whole gut lavage as well as oral neomycin sulfate/erythromycin estolate and perioperative parenteral cefazolin sodium (Ancef). Five wound infections (4.8%) occurred. Three infections were in the delayed primary closure group and one infection in each of the other two study groups. No statistical difference in wound infection was demonstrated. On the basis of the findings in this study, we would not recommend delayed primary closure for the management of colostomy closure wounds when careful mechanical and antibiotic preparation has been utilized.

An evaluation of hospital cleaning regimes and standards.

A four-part study assessing cleanliness in up to 113 environmental surfaces in an operating theatre and a hospital ward is reported. Surfaces were assessed visually, using microbiological methods and ATP bioluminescence. Results from a preliminary random survey indicated variability in cleanliness. These results were then used to select sites for monitoring before and after routine cleaning, over a 14-day period. Using published microbiological and ATP specifications 70 and 76% of these sites were unacceptable after cleaning. Visual assessment was a poor indicator of cleaning efficacy with only 18% considered unacceptable. Sites most likely to fail in the ward were in the toilet and kitchen, areas which are frequently implicated in the spread of infectious intestinal disease. Operating theatre sites had lower ATP results but 61% of sites would be considered unacceptable. There was no significant difference in general microbiological or ATP results overall before and after routine cleaning. Although some important hand contact sites showed no significant difference, overall there was a significant decrease in staphylococcal and enterobacteria counts in the ward but not in the operating theatre after cleaning. The routine cleaning programmes used did not include a biocide and cleaning using a hypochlorite based sanitizer gave much lower values. The results are discussed in relation to infection control, cleaning audits and cleaning schedules: an integrated cleaning monitoring programme using ATP bioluminescence in conjunction with visual and microbiological assessments is recommended.

Granulomatous mastitis can mimic breast cancer on clinical, radiological or cytological examination: a cautionary tale.

In both women and men, breast lumps are the most common presentation of breast cancer. The following cases illustrate the pathological entity of granulomatous mastitis, which can present simulating breast cancer - including the first description of this condition in a male. These cases demonstrate the difficulty in clinical diagnosis and emphasizes that although there may be clues from the history, clinical awareness that this condition can mimic breast cancer in all aspects of the triple assessment process should arouse suspicion. The importance of histological diagnosis by core or excision biopsy is stressed, as with accurate diagnosis of granulomatous mastitis there is a mandate to avoid unnecessary surgery.