Hemoglobin vesicles improve wound healing and tissue survival in critically ischemic skin in mice

Local hypoxia, as due to trauma, surgery, or arterial occlusive disease, may severely jeopardize the survival of the affected tissue and its wound-healing capacity. Initially developed to replace blood transfusions, artificial oxygen carriers have emerged as oxygen therapeutics in such conditions. The aim of this study was to target primary wound healing and survival in critically ischemic skin by the systemic application of left-shifted liposomal hemoglobin vesicles (HbVs). This was tested in bilateral, cranially based dorsal skin flaps in mice treated with a HbV solution with an oxygen affinity that was increased to a P(50) (partial oxygen tension at which the hemoglobin becomes 50% saturated with oxygen) of 9 mmHg. Twenty percent of the total blood volume of the HbV solution was injected immediately and 24 h after surgery. On the first postoperative day, oxygen saturation in the critically ischemic middle flap portions was increased from 23% (untreated control) to 39% in the HbV-treated animals (P < 0.05). Six days postoperatively, flap tissue survival was increased from 33% (control) to 57% (P < 0.01) and primary healing of the ischemic wound margins from 6.6 to 12.7 mm (P < 0.05) after HbV injection. In addition, higher capillary counts and endothelial nitric oxide synthase expression (both P < 0.01) were found in the immunostained flap tissue. We conclude that left-shifted HbVs may ameliorate the survival and primary wound healing in critically ischemic skin, possibly mediated by endothelial nitric oxide synthase-induced neovascularization.

Keratitis resulting from Thielavia subthermophila Mouchacca

PURPOSE: The purpose of this study was to report the first case of fungal keratitis resulting from Thielavia sp. METHODS: We conducted a retrospective chart review. RESULTS: A 10-year old girl presented 2 weeks after ocular plant injury with pain and corneal stromal infiltration with central ulceration and ill-defined margins. Cultures of corneal scrapings and biopsy sequence analysis of the ribosomal internal transcribed spacer region isolated Thielavia subthermophila Mouchacca. Clinically, the organism appeared to respond to topical amphotericin B and oral voriconazole. Best-corrected visual acuity at last follow-up visit counted 0.5. CONCLUSIONS: A rare case of Thielavia sp. keratitis was successfully treated with topical amphotericin B and oral voriconazole. Newly developed molecular diagnostic tools contribute to the recognition of a widening spectrum of emerging fungal pathogens capable of causing serious ocular infections.

Rick Henderson and Mike Pochin: A Right Result? Advocacy, justice and empowerment

As Henderson and Pochin point out in the introduction to their book, recent years have seen the concept of advocacy given increasing prominence in central and local government policy in the UK. It made an appearance in local community care and long-stay hospital closure plans. It features in reforms to the health service in England and Wales, in the form of the Patient Advocacy and Liaison Services (DoH 2000), while proposed changes to the mental health system also accord a key role to service users' advocates. In addition, Valuing People, central government's proposals on the future strategy for people with learning disabilities, promised the widespread development of advocacy services (DoH 2001). Advocacy, traditionally located on the margins of state activity in the UK, is experiencing something of an attempt to shift it into mainstream policy and service provision. This makes it a significant time to review the core values and practices that have distinguished advocacy from other forms of professional and voluntary intervention and to explore how these may be preserved and developed in the contemporary context.

Hormographiella aspergillata keratomycosis in a dog

A 4-year-old, female, Border Collie was presented to the University of Bern Veterinary Teaching Hospital, because of a corneal lesion of 10 days duration. The axial cornea presented a whitish fluorescein-positive plaque with irregular margins. A diagnosis of keratomycosis was made based on cytology. Medical therapy with local broad-spectrum antibiotic and fluconazole was instituted. After 1 week of treatment, the improvement was deemed unsatisfactory. Therefore, a lamellar keratectomy and conjunctival pedicle flap were performed. After surgery, the cornea healed uneventfully. Histology confirmed the diagnosis of keratomycosis. The fungus could not be grown in culture and a precise etiological diagnosis could only be obtained with genetic identification of the fungus. A PCR technique was used to amplify the fungal genome from the cornea. Hormographiella aspergillata, the asexual reproductive form of the basidiomycete Coprinopsis cinerea, was identified. As advised in human medicine, we encourage the use of this molecular technique to obtain an early species diagnosis, allowing targeted medical therapy.

Evaluation of endosonography as a new diagnostic tool for feline pancreatitis

The purpose of this study was to evaluate endosonography (EUS) as a potential diagnostic tool for feline pancreatitis. Eleven healthy cats and six cats diagnosed with pancreatitis based on an increased serum feline pancreatic lipase immunoreactivity (fPLI) concentration were included. Transabdominal ultrasound (AUS) and EUS were performed in all cats. The widths of both pancreatic limbs and echogenicity and homogenicity were assessed by AUS and EUS. Finally, findings from both modalities were subjectively compared. In the healthy cats, the right pancreatic limb was significantly smaller on EUS compared to AUS. Also, subjectively, general visualization of the normal pancreas was superior with EUS and, the pancreatic margins and parenchyma could be resolved better with EUS in all sick patients. In this study, EUS findings did not alter the diagnosis in six cats with pancreatitis when compared to AUS. However, EUS may be useful in cases where AUS fails due to obesity, hyperechoic mesentery, or excessive intestinal gas.

An economic assessment of drought effects on three grassland systems in Switzerland

This paper analyzes the economic impacts of summer drought on Swiss grassland production. We combine field trial data from drought experiments in three different grasslands in Switzerland with site-specific information on economic costs and benefits. The analysis focuses on the economic implications of drought effects on grassland yields as well as grassland composition. In agreement with earlier studies, we found rather heterogeneous yield effects of drought on Swiss grassland systems, with significantly reduced yields as a response to drought at the lowland and sub-alpine sites, but increased yields at the wetter pre-alpine site. Relative yield losses were highest at the sub-alpine site (with annual yield losses of up to 37 %). However, because income from grassland production at extensive sites relies to a large extent on ecological direct payments, even large yield losses had only limited implications in terms of relative profit reductions. In contrast, negative drought impacts at the most productive, intensively managed lowland site were dominant, with average annual drought-induced profit margin reductions of about 28 %. This is furthermore emphasized if analyzing the farm level perspective of drought impacts. Combining site-specific effects at the farm level, we found that in particular farms with high shares of lowland grassland sites suffer from summer droughts in terms of farm-level fodder production and profit margins. Moreover, our results showed that the higher competitiveness of weeds (broad-leaved dock) under drought conditions will require increasing attention on weed control measures in future grassland production systems. Taking into account that the risk of drought occurrence is expected to increase in the coming years, additional instruments to cope with drought risks in fodder production and finally farmers’ income have to be developed.

Management Intensive Grazing of Stockers at the Andrew Jackson Demonstration Farm (1996 – 1998)

The Andrew Jackson Demonstration Farm (AJDF) is located in central Jackson County in east central Iowa. A board of directors operates the farm for the purpose of demonstrating different production practices and management strategies. From 1996 to 1998 management intensive grazing practices and the grazing of stockers on a combination of permanent and tillable pasture have been demonstrated. Grazing strategies or practices demonstrated during these years included establishment of Eastern Gamagrass and Big Bluestem, variable density grazing, measuring forage on-offer, estimating dry matter intake, grazing corn, pasture renovation, and fencing and water systems. Production performance data were gathered for the three years stockers that were grazed. During this time the stockers averaged 121 animal days of grazing, a 1.1 head per acre stocking rate, a 1.85 pound average daily gain, and 228 pounds of gain per acre. The financial measures evaluated the value of gain on pasture and the pasture cost of the gain. The value of gain per pound was positive for 1996 and 1997 at $.58 and $.52 whereas in 1998 it was a -$.04. Pasture costs per pound of gain ranged from $.12 to $.16. Production performance is only one part of the profit picture when evaluating a stocker operation. Buysell margins are the other significant part that can greatly impact the profit potential of a summer grazing program.

Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.

BACKGROUND Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients. METHODS The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152. FINDINGS From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection. INTERPRETATION Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative. FUNDING US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Intraoperative fabrication of patient-specific moulded implants for skull reconstruction: single-centre experience of 28 cases

BACKGROUND Intraoperatively fabricated polymethylmethacrylate (PMMA) implants based on computer-designed moulds were used to improve cosmetic results after hard tissue replacement. To assess the implant's cosmetic and functional results we performed both subjective and objective assessments. METHODS This retrospective analysis was performed using a cohort of 28 patients who received PMMA implants between February 2009 and March 2012. The cosmetic and functional results were assessed using a patient questionnaire. Furthermore an objective volumetric subtraction score (0-100) was applied and implant thickness, as well as gaps and tiers, were measured. RESULTS Patients mainly judged their cosmetic result as "good". Two of the 28 patients found their cosmetic result unfavourable. The functional result and stability was mainly judged to be good. Measurements of implant thickness showed a very high correlation with the thickness of the contralateral bone. Volumetric subtraction led to a median quality of 80 on a scale from 0 to 100. Median gaps around the margins of the implant were 1.5 mm parietally, 1.7 mm frontally and 3.5 mm fronto-orbitally, and median tiers were 1.2 mm, 0 mm and 0 mm respectively. The overall rate of surgical revisions was 10.7 % (three patients). Two patients suffered from wound healing disturbances (7.1 %). The overall complication rate was comparable to other reports in the literature. CONCLUSIONS Implantation of intraoperatively fabricated patient-specific moulded implants is a cost-effective and safe technique leading to good clinical results with a low complication rate.

Observations of the northern seasonal polar cap on Mars: I. Spring sublimation activity and processes

Spring sublimation of the seasonal CO2 northern polar cap is a dynamic process in the current Mars climate. Phenomena include dark fans of dune material propelled out onto the seasonal ice layer, polygonal cracks in the seasonal ice, sand flow down slipfaces, and outbreaks of gas and sand around the dune margins. These phenomena are concentrated on the north polar erg that encircles the northern residual polar cap. The Mars Reconnaissance Orbiter has been in orbit for three Mars years, allowing us to observe three northern spring seasons. Activity is consistent with and well described by the Kieffer model of basal sublimation of the seasonal layer of ice applied originally in the southern hemisphere. Three typical weak spots have been identified on the dunes for escape of gas sublimed from the bottom of the seasonal ice layer: the crest of the dune, the interface of the dune with the interdune substrate, and through polygonal cracks in the ice. Pressurized gas flows through these vents and carries out material entrained from the dune. Furrows in the dunes channel gas to outbreak points and may be the northern equivalent of southern radially-organized channels ("araneiform" terrain), albeit not permanent. Properties of the seasonal CO2 ice layer are derived from timing of seasonal events such as when final sublimation occurs. Modification of dune morphology shows that landscape evolution is occurring on Mars today, driven by seasonal activity associated with sublimation of the seasonal CO2 polar cap.

Augmented environments for the targeting of hepatic lesions during image-guided robotic liver surgery

BACKGROUND Stereotactic navigation technology can enhance guidance during surgery and enable the precise reproduction of planned surgical strategies. Currently, specific systems (such as the CAS-One system) are available for instrument guidance in open liver surgery. This study aims to evaluate the implementation of such a system for the targeting of hepatic tumors during robotic liver surgery. MATERIAL AND METHODS Optical tracking references were attached to one of the robotic instruments and to the robotic endoscopic camera. After instrument and video calibration and patient-to-image registration, a virtual model of the tracked instrument and the available three-dimensional images of the liver were displayed directly within the robotic console, superimposed onto the endoscopic video image. An additional superimposed targeting viewer allowed for the visualization of the target tumor, relative to the tip of the instrument, for an assessment of the distance between the tumor and the tool for the realization of safe resection margins. RESULTS Two cirrhotic patients underwent robotic navigated atypical hepatic resections for hepatocellular carcinoma. The augmented endoscopic view allowed for the definition of an accurate resection margin around the tumor. The overlay of reconstructed three-dimensional models was also used during parenchymal transection for the identification of vascular and biliary structures. Operative times were 240 min in the first case and 300 min in the second. There were no intraoperative complications. CONCLUSIONS The da Vinci Surgical System provided an excellent platform for image-guided liver surgery with a stable optic and instrumentation. Robotic image guidance might improve the surgeon's orientation during the operation and increase accuracy in tumor resection. Further developments of this technological combination are needed to deal with organ deformation during surgery.

Implementation of an Anthropomorphic Phantom for the Evaluation of Proton Therapy Treatment Procedures

With an increasing number of institutions offering proton therapy, the number of multi-institutional clinical trials involving proton therapy will also increase in the coming years. The Radiological Physics Center monitors sites involved in clinical trials through the use of site visits and remote auditing with thermoluminescent dosimeters (TLD) and mailable anthropomorphic phantoms. Currently, there are no heterogeneous phantoms that have been commissioned to evaluate proton therapy. It was hypothesized that an anthropomorphic pelvis phantom can be designed to audit treatment procedures (patient simulation, treatment planning and treatment delivery) at proton facilities to confirm agreement between the measured dose and calculated dose within 5%/3mm with a reproducibility of 3%. A pelvis phantom originally designed for use with photon treatments was retrofitted for use in proton therapy. The relative stopping power (SP) of each phantom material was measured. Hounsfield Units (HU) for each phantom material were measured with a CT scanner and compared to the relative stopping power calibration curve. The tissue equivalency for each material was calculated. Two proton treatment plans were created; one which did not correct for material SP differences (Plan 1) and one plan which did correct for SP differences (Plan 2). Film and TLD were loaded into the phantom and the phantom was irradiated 3 times per plan. The measured values were compared to the HU-SP calibration curve and it was found that the stopping powers for the materials could be underestimated by 5-10%. Plan 1 passed the criteria for the TLD and film margins with reproducibility under 3% between the 3 trials. Plan 2 failed because the right-left film dose profile average displacement was -9.0 mm on the left side and 6.0 mm on the right side. Plan 2 was intended to improve the agreements and instead introduced large displacements along the path of the beam. Plan 2 more closely represented the actual phantom composition with corrected stopping powers and should have shown an agreement between the measured and calculated dose within 5%/3mm. The hypothesis was rejected and the pelvis phantom was found to be not suitable to evaluate proton therapy treatment procedures.

Thoracic radiotherapy treatment planning with cine PET/CT

Purpose: Respiratory motion causes substantial uncertainty in radiotherapy treatment planning. Four-dimensional computed tomography (4D-CT) is a useful tool to image tumor motion during normal respiration. Treatment margins can be reduced by targeting the motion path of the tumor. The expense and complexity of 4D-CT, however, may be cost-prohibitive at some facilities. We developed an image processing technique to produce images from cine CT that contain significant motion information without 4D-CT. The purpose of this work was to compare cine CT and 4D-CT for the purposes of target delineation and dose calculation, and to explore the role of PET in target delineation of lung cancer. Methods: To determine whether cine CT could substitute 4D-CT for small mobile lung tumors, we compared target volumes delineated by a physician on cine CT and 4D-CT for 27 tumors with intrafractional motion greater than 1 cm. We assessed dose calculation by comparing dose distributions calculated on respiratory-averaged cine CT and respiratory-averaged 4D-CT using the gamma index. A threshold-based PET segmentation model of size, motion, and source-to-background was developed from phantom scans and validated with 24 lung tumors. Finally, feasibility of integrating cine CT and PET for contouring was assessed on a small group of larger tumors. Results: Cine CT to 4D-CT target volume ratios were (1.05±0.14) and (0.97±0.13) for high-contrast and low-contrast tumors respectively which was within intraobserver variation. Dose distributions on cine CT produced good agreement (< 2%/1 mm) with 4D-CT for 71 of 73 patients. The segmentation model fit the phantom data with R2 = 0.96 and produced PET target volumes that matched CT better than 6 published methods (-5.15%). Application of the model to more complex tumors produced mixed results and further research is necessary to adequately integrate PET and cine CT for delineation. Conclusions: Cine CT can be used for target delineation of small mobile lesions with minimal differences to 4D-CT. PET, utilizing the segmentation model, can provide additional contrast. Additional research is required to assess the efficacy of complex tumor delineation with cine CT and PET. Respiratory-averaged cine CT can substitute respiratory-averaged 4D-CT for dose calculation with negligible differences.