Snow patch refugia benefits for species of periglacial zones-Evidence from a high-elevation obligate.

Conserving Earth's most rapidly changing biomes necessitates understanding biological consequences of altered climes. Past species- and taxa-level responses to warming environs include numerous concentrated extirpations at the southern peripheries of distributions during the late Pleistocene. Less clear are localized capacities of cold-adapted species to mitigate thermal challenges against warming temperatures, especially through proximate behavioral and physiological adjustments. Whereas snow patches persist in periglacial zones and elsewhere, broad reductions in seasonal snow raise concerns about how and why species continue to use them. If snow patches play a functional role to combat increasing thermal demands, we predicted individuals would display an array of autonomic responses to increased temperatures modulated by wind, ambient temperature, and winter fur on and away from snow patches. We tested these predictions using a mammalian exemplar of high latitude and high elevation, mountain goats (Oreamnos americanus), using two sites in the northern Rocky Mountains, USA. Surprisingly, and contrary to expectations of reduced thermal stress, respiration rates were not decreased on snow patches but use of snow was strongly correlated with decreased metrics of insect harassment. As snow cover continues to decline in montane environs, the persistence of cold-adapted species depends on navigating concurrent changes in biotic communities and thermal environments and balancing competing pressures on behavioral and biological responses.

An implementation history of primary health care transformation: Alberta's primary care networks and the people, time and culture of change.

BACKGROUND: Primary care, and its transformation into Primary Health Care (PHC), has become an area of intense policy interest around the world. As part of this trend Alberta, Canada, has implemented Primary Care Networks (PCNs). These are decentralized organizations, mandated with supporting the delivery of PHC, funded through capitation, and operating as partnerships between the province's healthcare administration system and family physicians. This paper provides an implementation history of the PCNs, giving a detailed account of how people, time, and culture have interacted to implement bottom up, incremental change in a predominantly Fee-For-Service (FFS) environment. METHODS: Our implementation history is built out of an analysis of policy documents and qualitative interviews. We conducted an interpretive analysis of relevant policy documents (n = 20) published since the first PCN was established. We then grounded 12 semi-structured interviews in that initial policy analysis. These interviews explored 11 key stakeholders' perceptions of PHC transformation in Alberta generally, and the formation and evolution of the PCNs specifically. The data from the policy review and the interviews were coded inductively, with participants checking our emerging analyses. RESULTS: Over time, the PCNs have shifted from an initial Frontier Era that emphasized local solutions to local problems and featured few rules, to a present Era of Accountability that features central demands for standardized measures, governance, and co-planning with other elements of the health system. Across both eras, the PCNs have been first and foremost instruments and supporters of family physician authority and autonomy. A core group of people emerged to create the PCNs and, over time, to develop a long-term Quality Improvement (QI) vision and governance plan for them as organizations. The continuing willingness of both these groups to work at understanding and aligning one another's cultures to achieve the transformation towards PHC has been central to the PCNs' survival and success. CONCLUSIONS: Generalizable lessons from the implementation history of this emerging policy experiment include: The need for flexibility within a broad commitment to improving quality. The importance of time for individuals and organizations to learn about: quality improvement; one another's cultures; and how best to support the transformation of a system while delivering care locally.

Integrating the social sciences into the COVID-19 response in Alberta, Canada.

This paper outlines the rapid integration of social scientists into a Canadian province's COVID-19 response. We describe the motivating theory, deployment and initial outcomes of our team of Organisational Sociologist ethnographers, Human Factors experts and Infection Prevention and Control clinicians focused on understanding and improving Alberta's responsiveness to the pandemic. Specifically, that interdisciplinary team is working alongside acute and primary care personnel, as well as public health leaders to deliver 'situated interventions' that flow from studying communications, interpretations and implementations across responding organisations. Acting in real time, the team is providing critical insights on policy communication and implementation to targeted members of the health system. Using our rapid and ongoing deployment as a case study of social science techniques applied to a pandemic, we describe how other health systems might leverage social science to improve their preparations and communications.

Cutting Through the Ice .

The papers that follow are part of an honest, reasonable and serious attempt to build on an existing consensus at the basis of medicare, which guarantees that all Canadians can get medical attention when sick and hospital care when very sick (or injured). Without any exception, reform proposals that run counter to these principles are doomed to failure. However, it becomes harder and harder to ensure that costly and complex healthcare services can be "readily and timely" accessed without a radical shift in approaches. To say things otherwise, to keep what we cherish, we must embrace change, in the form of collaboration, measurement and evidence.

Squamous anal cancer: patient characteristics and HPV type distribution.

BACKGROUND: Infection with high risk human papillomavirus (HPV) is strongly associated with anal cancer. However, detailed studies on HPV type distribution by gender and age are limited. METHODS: Retrospective study of 606 invasive anal cancers diagnosed between 1990 and 2005 in two large urban areas of the province of Québec, Canada. Cases were identified from hospitalization registry. Patient characteristics were collected from medical files. Archived anal squamous cancer specimens were available from 96 patients and were tested for HPV DNA and typing. Variant analysis was performed on 16 consecutive and 24 non-consecutive HPV16-positive samples to assess potential contamination during amplification. RESULTS: Among the 606 patients with anal cancers, 366 (60%) were women. Median age at diagnosis was 63 years. HPV was detected in 88/96 (92%) of cases. HPV16 was the most frequent type detected in 90% of HPV-positive specimens. Other types including 6, 11, 18, 33, 52, 53, 56, 58, 62 and 82 were also found. HPV 97 was not detected. HPV prevalence was associated with female gender and younger age. No contamination occurred during amplification as shown by the subset of 41 HPV16-positive samples, as 37, 2 and 1 isolates were from the European, African and Asian lineages, respectively. The most frequent variants were G1 (n=22) and the prototype (n=12). CONCLUSIONS: Women with anal cancer are at higher risk for anal HPV infection, and HPV infection, especially HPV16, is strongly associated with squamous anal cancer. Therefore, HPV vaccine could potentially prevent the occurrence of anal cancer in both men and women.

Validation of a viral and bacterial inactivation step during the extraction and purification process of porcine collagen.

In the last few years, regulations for biomolecule production, and especially for extraction and purification of animal molecules such as collagen, have been reinforced to ensure the sanitary safety of the materials. To be authorized to market biomaterials based on collagen, manufacturers now have to prove that at least one step of their process is described in guidelines to inactivate prion, viruses, and bacteria. The present study focuses on the inactivation step performed during the extraction and purification of porcine type I atelocollagen. We chose to determine the reduction factor of a 1 M NaOH step on porcine parvovirus and four bacterial strains inactivation. During the extraction step, we deliberately inoculated the collagen suspension with the different microorganisms tested. Then, 1 M NaOH was added to the suspension for 1 hour at 20 degrees C. We demonstrated that this treatment totally inactivated S. aureus, P. aeruginosa, C. albicans and A. niger which are bacterial strains responsible of severe human pathology. The reduction factors reached more than 4 logs for B. cereus spores and 4 logs for the porcine parvovirus. are encouraging as those two microorganisms are known to be very resistant to inactivation.

Influence of gradual introduction of hydrophobic groups (stearic acid) in denatured atelocollagen on fibroblasts behavior in vitro.

To prepare new biocompatible hydrophobic collagen films for medical devices, innovative collagen derivatives were synthesized by reaction of the lysyl amino groups of the alpha-chains with activated stearic acid. Different collagens having different substitution degrees were obtained and used to prepare films crosslinked with oxidized glycogen. Their physicochemical surface properties were evaluated, and in vitro assays were performed to analyze the behavior of fibroblasts in contact with the materials. The assays were performed with cells in adhesion and growth phases. The hydrophobic properties increased with the number of stearic acid introduced in the collagen but only in the range of 1-12 stearic acids per molecule. For higher modifications a decrease of hydrophoby was observed. All the films induced a decrease of cells growth and adhesion but without cytotoxicity. These effects were more pronounced for the collagen containing about eight stearic acid residues. Cells behavior on modified collagens films seems to be related to the chemical groups exposed on the surface of the films. Indeed, the surface chemistry directly influences the adsorption of adhesion proteins and modulates their conformation therefore modifying the cell adhesion.

Detection of human papillomavirus type 16 DNA in consecutive genital samples does not always represent persistent infection as determined by molecular variant analysis.

Persistent human papillomavirus (HPV) infection of the uterine cervix is a risk factor for progression to high-grade squamous intraepithelial lesions. Detection in consecutive genital samples of HPV-16 DNA, a frequently encountered HPV type, may represent persistent infection or reinfection. We undertook a study using PCR-single-strand conformation polymorphism (SSCP) analysis and sequencing of PCR products (PCR-sequencing) to determine if consecutive HPV-16-positive samples contained the same HPV-16 variant. Fifty women (36 human immunodeficiency virus [HIV] seropositive, 14 HIV seronegative) had at least two consecutive genital specimens obtained at 6-month intervals that contained HPV-16 DNA as determined by a consensus L1 PCR assay. A total of 144 samples were amplified with two primer pairs for SSCP analysis of the entire long control region. Fifteen different SSCP patterns were identified in our population, while 22 variants were identified by PCR-sequencing. The most frequent SSCP pattern was found in 75 (53%) samples from 27 (54%) women. The SSCP patterns obtained from consecutive specimens were identical for 46 (92%) of 50 women, suggesting persistent infection. Four women exhibited in consecutive specimens different HPV-16 SSCP patterns that were all confirmed by PCR-sequencing. The additional information on the nature of persistent infection provided by molecular variant analysis was useful for 6% of women, since three of the four women who did not have identical consecutive specimens would have been misclassified as having persistent HPV-16 infection on the basis of HPV typing.

Evaluation of a vanA-specific PCR assay for detection of vancomycin-resistant Enterococcus faecium during a hospital outbreak.

We investigated the use of PCR as an alternative to culture of fecal samples for detection of vanA-containing Enterococcus faecium during a recent hospital outbreak. Rectal swabs collected consecutively from 223 patients were analyzed by culture with and without enrichment broth and by vanA-specific PCR of enrichment broth samples. Fifty-five specimens were positive for vanA-containing E. faecium by at least one method. The sensitivities of the vanA-specific PCR assay and agar culture with and without enrichment broth were 94.5, 98, and 89%, respectively. All three methods were 100% specific. Final results were obtained much more rapidly by PCR (within 24 to 30 h of specimen submission) than by the culture methods (4 to 5 days). Thus, PCR is an accurate and rapid alternative to culture for detection of vancomycin-resistant enterococci during hospital outbreaks.

Continuous infusion, intravesical doxorubicin for the treatment of regionally advanced bladder cancer: a phase I-II trial.

Patients with regionally advanced bladder cancer not considered candidates for definitive surgical intervention underwent continuous antegrade infusion of doxorubicin by percutaneous nephrostomy tube. Doxorubicin was administered for 7 consecutive days at a rate designed to achieve target urinary concentrations (range 5-80 micrograms/ml). Urine and serum concentrations of doxorubicin were monitored daily. Toxicity was assessed by serial renal scans, antegrade nephrostograms, blood counts, and serum chemistries. Patients were restaged after three cycles of therapy. In all, 23 cycles, constituting 156 days of therapy, were administered to 10 patients. Target urinary drug levels were achieved during all cycles. Total doxorubicin dose ranged from 125 to 2,500 mg. No systemic (neutropenia or myocardial dysfunction) or regional toxicity (extravasation, sepsis, stricture) was noted. Five of 10 patients tolerated the planned three treatment cycles. Poor performance status (PS, Eastern Cooperative Oncology Group: ECOG 3) strongly correlated with treatment intolerance and early death from disease. After three cycles of therapy, 2 of 5 evaluable patients had stable disease, I had radiographic partial response (PR) with a biopsy demonstrating extensive tumor necrosis, I had no identifiable tumor at the time of restaging transurethral resection of bladder tumor (TURBT), and a final patient with upper and lower tract carcinoma in situ (CIS) was cytologically staged NED. (no evidence of disease). These findings demonstrate the feasibility and low toxicity of this approach.

A phase II trial of deferoxamine in patients with hormone-refractory metastatic prostate cancer.

The management of hormone-refractory metastatic prostate cancer remains a therapeutic dilemma. We report the results of a phase II trial with deferoxamine administrated at a dose of 50 mg/kg (maximum dose 5 g) administered intravenously over 8 hr daily, repeated for 5 days at 4-week intervals for 2 courses. Fourteen patients with advanced hormone-refractory prostate cancer were treated and 28 courses were delivered. Essentially no toxicity was observed. Using combined clinical and prostate-specific antigen (PSA) criteria. 13 of 14 patients had disease progression. However, 9 of 14 patients had stable measurable or evaluable disease and progressed solely based on PSA criteria. Deferoxamine in this dose and schedule has no activity in hormone-refractory prostate cancer. Further investigation of the effect of deferoxamine on PSA production/expression is warranted.

Brachytherapy and continuous infusion 5-fluorouracil for treatment of locally advanced, lymph node negative, prostate cancer: a phase I trial.

BACKGROUND: 5-fluorouracil (5-FU) is a known radiosensitizer that enhances efficacy, in vivo and in vitro, when administered during radiotherapy. The following study was performed to evaluate the toxicity of continuous infusion 5-FU administered concomitant with brachytherapy in patients with locally advanced prostate cancer. METHODS: Over a 26-month period, a total of 25 patients with newly diagnosed, locally advanced prostate cancer underwent radioactive gold (Au198) brachytherapy. Twenty-four of 25 patients were surgically staged and confirmed node negative. Au198 seed placement was performed transperineally under fluoroscopic and ultrasonographic guidance using an average of 195 mCi of Au198. Within 4 hours after seed placement, 25 patients received 5-FU administered as a continuous infusion over 4 days, at 1 of 8 dose levels ranging from 200-1100 mg/m2/day. Patients had clinical follow-up for a minimum of 1 year. Decreases in serum prostate specific antigen (PSA) and prostate volume (normalized to pretreatment values) were determined at 12 months. RESULTS: 5-FU associated toxicity was negligible, with Grade 1 nausea in four patients and no Grade 2 or higher toxicity. No unique locoregional toxicity was noted. At 12 months after treatment, PSA values decreased on average to 16.4% of pretreatment values. Twelve-month prostate volumes decreased to 55% of the pretreatment values. CONCLUSIONS: These findings suggest that continuous infusion 5-FU can be administered safely concomitant with brachytherapy at doses up to 1100 mg/m2 per day for 4 days.

Phase II trial of 5-fluorouracil and alpha-2b interferon in patients with hormone-refractory metastatic prostate cancer.

OBJECTIVES: Metastatic prostate cancer remains a disease with no effective therapy. We treated 13 patients with hormone-refractory metastatic prostate cancer with 5-fluorouracil (5-FU) and alpha-2b interferon. Our objectives were to determine the response rate and toxicity of recombinant alpha interferon and 5-FU in patients with hormone-refractory metastatic prostate cancer. METHODS: Patients with progressive hormone-refractory metastatic prostate cancer with adequate hematologic and renal function underwent baseline bone scans, computed tomographic (CT) scans of abdomen and pelvis, and measurement of prostate-specific antigen (PSA). Therapy consisted of a 5-day loading course of 5-FU at 500 mg/m2 with alpha-2b interferon 9 million units subcutaneously 3 times weekly followed by weekly 5-FU and alpha interferon 3 times per week. RESULTS: When PSA was used as a response parameter with modified National Prostatic Cancer Project (NPCP) criteria, no objective responses were seen. Using NPCP criteria alone, 5 patients had stable disease. Post-therapy PSA values increased from baseline in 8 of 11 patients (2% to 72%) and declined in 3 patients (3% to 16%). Frequent dosage modifications were required with the dose intensity of 5-FU and alpha interferon of 57% and 58%, respectively. Toxicity was significant, with 31% of patients having grade 3 to 4 mucositis and 46% grade 3 to 4 fatique. CONCLUSIONS: 5-FU and alpha interferon, when administered at the dosage and schedule utilized in this study, have no clinically significant activity and are associated with unacceptable toxicity in patients with metastatic prostate cancer. The role of PSA as an indicator of response remains unclear.

Analysis of genes encoding highly conserved lysine-rich proteins in Aplysia californica and Saccharomyces cerevisiae.

To isolate a gene that can be used as an internal control in studies on gene expression in Aplysia californica neurons, we have characterized a cDNA clone (pKRP-A) isolated on the basis of its high expression in A. californica neurons. This cDNA is of 850 nucleotides and codes for a putative 29-kDa lysine-rich protein. Blotting experiments revealed that the gene is expressed in all tested A. californica tissues, and in individually identified neurons of the abdominal ganglion, suggesting that this gene can be efficiently used as internal control in studies of gene expression. We have also isolated one cDNA and two different genomic clones from yeast libraries that show 59% identity with pKRP-A. Sequence comparison of genomic clones, as well as PCR and Southern blotting experiments, revealed that at least two homologous genes are present in yeast. Northern blotting experiments revealed that the expression of the gene is strongly repressed at 39 degrees C.

Trajectory reconstructions. I: Trace evidence in flight.

This paper reviews the use of trace evidence recovered from spent bullets in helping to establish trajectories. The use of information derived from such trace evidence combined with that from geometrical techniques of trajectory reconstruction and other data is discussed. Five cases are reviewed in which the analysis of trace evidential materials adhering to bullets was used to help reconstruct the event.

The use of isoelectric focusing to identify rhinoceros keratins.

Keratins represent the principal structural proteins of hair. They are also found in horn, nail, claw, hoof, and feather. Hair and nail samples from human and canine sources and hair samples from mule deer, white tail deer, cat, moose, elk, antelope, caribou, raccoon, and goat were studied. Parrot and goose feathers were also analyzed. Keratins are polymorphic, and species differences are known to exist. Proteinaceous extracts of deer and antelope antlers and bovine and rhinoceros horn were prepared by solubilizing 10 mg of horn sample in 200 microL of a solution containing 12M urea, 74mM Trizma base, and 78mM dithiothreitol (DTT). Extraction took place over a 48-h period. A 25-microL aliquot of extract was removed and incubated with 5 microL of 0.1 M DTT for 10 min at 25 degrees C. Keratins were then separated by isoelectric focusing (IEF) on 5.2% polyacrylamide gels for 3 h and visualized using silver staining. At least 20 bands could be observed for each species studied. However, band patterns differed in the position of each band, in the number of bands, and in band coloration resulting from the silver staining process. Horn from two species of rhinoceros was examined. For both specimens, most bands occurred in the pH range of 4 to 5. Although similar patterns for both species were observed, they differed sufficiently to differentiate one from the other. As might be expected, the closer two species are related phylogenetically, the greater the similarity in the IEF pattern produced from their solubilized keratin.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of deoxyribonucleic acid (DNA) isolated from human bloodstains exposed to ultraviolet light, heat, humidity, and soil contamination.

This study was designed to analyze the effects of common environmental insults on the ability to obtain deoxyribonucleic acid (DNA) restriction fragment-length polymorphisms (RFLP) patterns from laboratory prepared specimens. The environmental conditions studied include the exposure of dried bloodstains to varying amounts of relative humidity (0, 33, 67, and 98%), heat (37 degrees C), and ultraviolet light for periods of up to five days. In addition, the effect of drying over a four-day period in whole blood collected with and without ethylenediaminetetraacetate (EDTA) was examined. The results of the study showed that, under the conditions studied, the integrity of DNA is not altered such that false RFLP patterns are obtained. The only effect observed was that the overall RFLP pattern becomes weaker, but individual RFLP fragments are neither created nor destroyed.