An Ontario Health (Cancer Care Ontario) Clinical Practice Guideline: Surveillance Strategies in Patients with Stage I, II, III or Resectable IV Melanoma Who Were Treated with Curative Intent.

AIMS: To make recommendations on managing the surveillance of patients with stage I, II, III or resectable IV melanoma who are clinically free of disease following treatment with curative intent. MATERIALS AND METHODS: This guideline was developed by Ontario Health's (Cancer Care Ontario's) Program in Evidence-Based Care and the Melanoma Disease Site Group (including seven medical oncologists, four surgical oncologists, three dermatologists, one radiation oncologist and one patient representative). The MEDLINE, EMBASE, Cochrane Library, PROSPERO databases and the main relevant guideline websites were searched. Internal and external reviews were conducted, with final approval by the Program in Evidence-Based Care and the Melanoma Disease Site Group. The Grading of Recommendations, Assessment, Development and Evaluation approach was followed, and the Modified Delphi method was used. RESULTS: Based on the current evidence (eight eligible original study papers and four relevant guidelines) and the clinical opinions of the authors of this guideline, the initial recommendations were made. To reach 75% agreement for each recommendation, the Melanoma Disease Site Group (16 members) voted twice and one recommendation was voted on three times. After a comprehensive internal and external review process (including national and international reviewers), 12 recommendations, three weak recommendations and six qualified statements were ultimately made. CONCLUSIONS: After a systematic review, a comprehensive internal and external review process and a consensus process, the current guideline has been created. The guideline authors believe that this guideline will help clinicians, patients and policymakers make well-informed healthcare decisions that will guide them in clinical melanoma surveillance and ultimately assist in improving patient outcomes.

Systemic adjuvant therapy for adult patients at high risk for recurrent cutaneous or mucosal melanoma: an Ontario Health (Cancer Care Ontario) clinical practice guideline.

Background: Previous versions of the guideline from the Program in Evidence-Based Care (pebc) at Ontario Health (Cancer Care Ontario) recommended that the use of high-dose interferon alfa 2b therapy be discussed and offered to patients with resected cutaneous melanoma with a high risk of recurrence. Subsequently, several clinical trials in patients with resected or metastatic melanoma found that immune checkpoint inhibitors and targeted therapies have a benefit greater than that with interferon. It was therefore considered timely for an update to the guideline about adjuvant systemic therapy in melanoma. Methods: The present guideline was developed by the pebc and the Melanoma Disease Site Group (dsg). Based on a systematic review from a literature search conducted using medline, embase, and the Evidence Based Medicine Reviews databases for the period 1996 to 28 May 2019, the Working Group drafted recommendations. The systematic review and recommendations were then circulated to the Melanoma dsg and the pebc Report Approval Panel for internal review; the revised document underwent external review. Recommendations: For patients with completely resected cutaneous or mucosal melanoma with a high risk of recurrence, the recommended adjuvant therapies are nivolumab, pembrolizumab, or dabrafenib-trametinib for patients with BRAF V600E or V600K mutations; nivolumab or pembrolizumab are recommend for patients with BRAF wild-type disease. Use of ipilimumab is not recommended. Molecular testing should be conducted to help guide treatment decisions. Interferon alfa, chemotherapy regimens, vaccines, levamisole, bevacizumab, bacillus Calmette-Guérin, and isolated limb perfusion are not recommended for adjuvant treatment of cutaneous melanoma except as part of a clinical trial.

Falloff Curves of the Reaction CF3 (+M) → CF2 + F (+M).

The thermal dissociation reaction CF3 (+Ar) → CF2 + F (+Ar) was studied in incident and reflected shock waves by monitoring UV absorption signals of the primary dissociation product CF2. CF3 radicals were produced by thermal decomposition of CF3I. Accounting for secondary reactions of F atoms, rate constants for the unimolecular dissociation were derived. Experimental parts of the falloff curves were obtained over the ranges 1544-2106 K and 1.0 × 10-5 ≤ [Ar] ≤ 9.3 × 10-5 mol cm-3. Theoretical modeling allowed for a construction of the full falloff curves connecting the limiting low-pressure rate constants k0 = [Ar] 2.5 × 1018 (T/2000 K)-5.1 exp (-42 450 K/T) cm3 mol-1 s-1 with the limiting high-pressure rate constants k∞ = 1.6 × 1016 (T/2000 K)-1.3 exp (-43 250 K/T) s-1 (center broadening factors of Fcent = 0.25, 0.22, and 0.20 at 1500, 2000, and 2500 K, respectively, were used). The influence of simplifications of falloff expressions and of limiting rate constants on the representation of experimental data is discussed.

Experimental and modelling study of the multichannel thermal dissociations of CH3F and CH2F.

The thermal unimolecular dissociation of CH3F was studied in shock waves by monitoring the UV absorption of a dissociation product identified as CH2F. It is concluded that, under conditions applied, the formation of this species corresponds to a minor, spin-allowed, dissociation channel of about 3% yield. Near to the low-pressure limit of the reaction, on the other hand, the energetically more favourable dissociation leads to 3CH2 + HF on a dominant, spin-forbidden, pathway. By considering the multichannel character of the reaction, it is shown that, in contrast to the low-pressure range, the high-pressure range of the reaction should be dominated by CH2F formation. The channel-switching probably takes place at pressures higher than those applied in the present work. In addition to the two dissociation channels of CH3F producing 3CH2 + HF and CH2F + H, a third, spin-allowed, dissociation channel leading to 1CHF + H2 was also considered and estimated to proceed with a yield smaller than 0.5%. Besides the dissociation of CH3F, the dissociation of CH2F was studied by monitoring the UV spectrum of CH2F. Details of this spectrum were investigated. Similar to CH3F, the dissociation of CH2F can proceed on several dissociation channels, under the present conditions either to CHF + H or to CF + H2. After modelling single-channel falloff curves for all reaction pathways, coupling effects of multichannel dissociations were interpreted in the framework of multichannel unimolecular rate theory.

Staging and surgical approaches in gastric cancer: a clinical practice guideline.

BACKGROUND: Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level, including staging, extent of lymphadenectomy (lnd), minimum number of lymph nodes that have to be assessed, gross resection margins, use of minimally invasive surgery, and relationship of surgical volumes with patient outcomes and resection in stage iv gastric cancer. METHODS: Literature searches were conducted in databases including medline (up to 10 June 2016), embase (up to week 24 of 2016), the Cochrane Library and various other practice guideline sites and guideline developer Web sites. A practice guideline was developed. RESULTS: One guideline, seven systematic reviews, and forty-eight primary studies were included in the evidence base for this guidance document. Seven recommendations are presented. CONCLUSIONS: All patients should be discussed at a multidisciplinary team meeting, and computed tomography (ct) imaging of chest and abdomen should always be performed when staging patients. Diagnostic laparoscopy is useful in the determination of M1 disease not visible on ct images. A D2 lnd is preferred for curative-intent resection of gastric cancer. At least 16 lymph nodes should be assessed for adequate staging of curative-resected gastric cancer. Gastric cancer surgery should aim to achieve an R0 resection margin. In the metastatic setting, surgery should be considered only for palliation of symptoms. Patients should be referred to higher-volume centres and those that have adequate support to manage potential complications. Laparoscopic resections should be performed to the same standards as those for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management.

Kinetic and Spectroscopic Studies of the Reaction of CF2 with H2 in Shock Waves.

The reaction of CF2 with H2 was studied in shock waves by monitoring UV absorption signals. CF2 was prepared by thermal dissociation of C2F4 (or of c-C3F6). The rate constant of the reaction CF2 + H2 → CHF + HF near 2000 K was found to be close to 1011 cm3 mol-1 s-1, consistent with earlier information on the reverse reaction CHF + HF → CF2 + H2 and a modeled equilibrium constant. The kinetic studies were accompanied by spectroscopic investigations. Absorption cross sections of C2F4 between 190 and 220 nm were measured near 1000 K and compared with room-temperature values from the literature. Likewise, absorption cross sections of CF2 near 2000 K were measured between 210 and 300 nm and compared with room-temperature data. Additional superimposed absorption signals were recorded during the reaction and identified by their time dependence and by quantum-chemical calculations employing time-dependent density functional theory. A previously unknown absorption spectrum of CHF radicals near 200 nm was identified and its wavelength dependence determined. Further strong absorptions between 190 and 300 nm were attributed to CH2F and CF radicals. Absorptions at longer wavelengths, reaching up to 510 nm, were postulated to arise from C2 radicals formed at later stages of the reaction.

Shock Wave and Theoretical Modeling Study of the Dissociation of CH2F2. II. Secondary Reactions.

The thermal dissociation of CH2F2 and the reaction of CF2 with H2 was studied in shock waves over the temperature range 1800-2200 K, monitoring the absorption-time profiles at 248 nm. Besides contributions from CF2, the signals showed strong absorptions from secondary reaction products, probably mostly CH2F formed by the reaction CHF + H2 → CH2F + H. Rate constants of a series of possible secondary reactions were modeled, including falloff curves for the thermal dissociations of CHF, CHF2, and CH2F and rate constants of the reactions CHF + CH2F2 → CHF2 + CH2F, CHF + H2 → CH2F + H, H + CH2F2 → CHF2 + H2, H + CF2 → CF + HF, and H + CF → C + HF. On this basis, concentration-time profiles were simulated and compared with experimental absorption-time profiles.

Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

BACKGROUND: Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. METHODS: We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. RESULTS: From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. CONCLUSION: Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

Isolation demand from carbapenemase-producing Enterobacteriaceae screening strategies based on a West London hospital network.

OBJECTIVE: To estimate the isolation demands arising from high-risk specialty-based screening for carbapenemase-producing Enterobacteriaceae (CPE), and the potential fraction of CPE burden detected. METHODS: Clinical specialty groups from three London hospitals were ranked by incidence of carbapenem resistance among Escherichia coli and Klebsiella spp. Contact precaution bed-days were estimated for three screening strategies: Strategy 1, 'circulation science and renal medicine'; Strategy 2, Strategy 1 plus 'specialist services'; and Strategy 3, Strategy 2 plus 'private patients'. Isolation bed occupancy rates and potential CPE detection rates were estimated. RESULTS: Of 99,105 admissions to the three hospitals in Financial Year 2014/15, Strategies 1, 2 and 3 would have screened 4371 (4.4%), 7482 (7.6%), and 13,542 (13.7%) patients, respectively. The specialties' isolation bed occupancy rates varied between 3% and 696% depending on strategy, number of consecutive tests, and whether or not pre-emptive isolation had been applied. Expected detection rates of the potential CPE burden in the hospital network would have varied between 17.1% and 47.5%. CONCLUSIONS: High-risk specialty-based screening has the potential to detect nearly half of the potential CPE burden, and would be more pragmatic than patient-level risk-factor-based screening. Pre-emptive isolation increases isolation requirements substantially. CPE screening strategies need to balance risk and resources.

Dental Student Academic Integrity in U.S. Dental Schools: Current Status and Recommendations for Enhancement.

Cheating incidents in 2006-07 led U.S. dental schools to heighten their efforts to enhance the environment of academic integrity in their institutions. The aims of this study were to document the measures being used by U.S. dental schools to discourage student cheating, determine the current incidence of reported cheating, and make recommendations for enhancing a culture of integrity in dental education. In late 2014-early 2015, an online survey was distributed to academic deans of all 61 accredited U.S. dental schools that had four classes of dental students enrolled; 50 (82%) responded. Among measures used, 98% of respondents reported having policy statements regarding student academic integrity, 92% had an Honor Code, 96% provided student orientation to integrity policies, and most used proctoring of final exams (91%) and tests (93%). Regarding disciplinary processes, 27% reported their faculty members only rarely reported suspected cheating (though required in 76% of the schools), and 40% disseminated anonymous results of disciplinary hearings. A smaller number of schools (n=36) responded to the question about student cheating than to other questions; those results suggested that reported cheating had increased almost threefold since 1998. The authors recommend that schools add cheating case scenarios to professional ethics curricula; disseminate outcomes of cheating enforcement actions; have students sign a statement attesting to compliance with academic integrity policies at every testing activity; add curricular content on correct writing techniques to avoid plagiarism; require faculty to distribute retired test items; acquire examination-authoring software programs to enable faculty to generate new multiple-choice items and different versions of the same multiple-choice tests; avoid take-home exams when assessing independent student knowledge; and utilize student assessment methods directly relevant to clinical practice.

The complex evolution of antibiotic resistance in Mycobacterium tuberculosis.

Multidrug-resistant and extensively drug-resistant tuberculosis (TB) represent a major threat to the control of the disease worldwide. The mechanisms and pathways that result in the emergence and subsequent fixation of resistant strains of Mycobacterium tuberculosis are not fully understood and recent studies suggest that they are much more complex than initially thought. In this review, we highlight the exciting new areas of research within TB resistance that are beginning to fill these gaps in our understanding, whilst also raising new questions and providing future directions.

Micropatterned, clickable culture substrates enable in situ spatiotemporal control of human PSC-derived neural tissue morphology.

We describe a modular culture platform that enables spatiotemporal control of the morphology of 2D neural tissues derived from human pluripotent stem cells (hPSCs) by simply adding clickable peptides to the media. It should be widely applicable for elucidating how spatiotemporal changes in morphology and substrate biochemistry regulate tissue morphogenesis.

Fitting form to function: reorganization of faculty roles for a new dental curriculum and its governance.

The College of Dentistry at the University of Illinois at Chicago has reorganized its predoctoral curriculum to better integrate biomedical, clinical, and behavioral sciences using a systems-based framework. The resulting D.M.D. curriculum features small-group discussions of patient scenarios that include orofacial, systemic, and professionalism learning objectives. Small-group learning is closely coordinated with laboratory, pre-patient care, and patient care experiences. Accordingly, the college has also reorganized its faculty roles to eliminate discipline-based silos and to better ensure program coherence. The new organizational structure is designed to improve coordination among faculty course teams that develop and administer individual courses, several units that provide curriculum resources and support services, and the curriculum committee, which is charged with governance of the curriculum as a whole. In addition, the new structure employs a system of reporting and planning relationships to ensure continuous monitoring and improvement of the curriculum. This article describes six principles that guide the new faculty roles structure, defines the various faculty roles and their coordinating relationships, presents diagrams depicting the organizational structures for curriculum governance, administration, and support, and discusses mechanisms for faculty support and continuous curriculum improvement.

Clinical evaluation of diamine silver fluoride/potassium iodide as a dentine desensitizing agent. A pilot study.

BACKGROUND: The aim of the present study was to compare the efficacy of an experimental diamine silver fluoride/potassium iodide product with an oxalic acid-based preparation in reducing dentine hypersensitivity. METHODS: The study was conducted as a double-blind, randomized clinical trial. A total of 19 subjects with dentine hypersensitivity on both sides of their upper arch were selected. The most sensitive tooth in each quadrant was identified and received a cold stimulus. The response was recorded on a visual analogue scale (VAS). The tooth thus selected was treated with one of the treatment agents. One week later the level of dentine sensitivity was assessed. Participants were also asked for their subjective assessment of treatment effects. RESULTS: The mean difference between VAS at baseline and seven days for teeth treated with diamine silver fluoride/potassium iodide was greater than that for teeth treated with the oxalic acid-based preparation (p = 0.0134). The subjects' subjective assessment of changes in dentine hypersensitivity indicated that more obtained relief with the diamine silver fluoride/potassium iodide treatment (p = 0.0129). CONCLUSIONS: It was concluded that an experimental diamine silver fluoride/potassium iodide product has potential as a treatment for dentine hypersensitivity.

Community-based dental education at the University of Illinois at Chicago.

Since 2002, community-based education at the University of Illinois at Chicago College of Dentistry (COD) has evolved from non-existent to a robust program that is an essential component of the predoctoral program. As part of the college's curricular innovation, community-based education has demonstrated alignment of the COD's mission with that of our parent institution, contributed significantly to student learning and preparedness, and enhanced clinic experiences and revenue. Student interest and support have been and continue to be enthusiastic and valued. The faculty has been generally supportive, but properly focused on demonstrated student learning outcomes. This faculty observation and evaluation, supported by evidence, has resulted in the faculty's rethinking traditional teaching and learning strategies, allowing innovative educational changes.

A model system for evaluating surface disinfection in dairy factory environments.

A model system was developed for evaluating the efficacy of disinfectants for inactivating bacteria present in biofilms on surfaces within dairy factory environments. Mixed culture biofilms of six dairy factory isolates (pseudomonads, coliforms and presumptive staphylococci) were generated on factory floor tiles and subjected to up to three fouling and cleaning (FC) cycles. Disinfectants (hypochlorite, peroxyacetic acid-, acid anionic- and quaternary ammonium compound (QUAT)-based products) were applied after cleaning at the supplier's recommended concentrations. Bacterial groups were enumerated using selective agar media. All disinfectants significantly (p<0.05) reduced surface counts of the three bacterial groups. The peroxyacetic acid-based product applied at 3.0% (v/v) achieved the greatest overall reductions in counts. In some cases, disinfectants were more biocidal towards particular bacterial groups. For example, hypochlorite demonstrated greater biocidal activity towards coliforms and staphylococci while the QUAT- and acid anionic-based disinfectants demonstrated greater biocidal activity towards staphylococci. The selective biocidal activity of hypochlorite and the acid anionic-based disinfectant was maintained over at least three FC cycles. The results demonstrate that disinfectants can alter the composition of the surface microflora and can be used to selectively reduce or eliminate particular bacterial groups from production environments. The model system was adapted to assess biofilm development and inactivation on a range of floor materials used in dairy factory environments. Clear differences were observed between surface materials at the end of the inoculation stage and following one FC cycle. For example, after one FC cycle, the highest bacterial counts were obtained for extruded floor tiles and the lowest for stainless steel and the polyurethane surface coating. The model system is versatile and there is scope to employ it to investigate a range of factors influencing the efficacy of cleaning and disinfection procedures towards biofilms. In addition, other microorganisms, such as pathogenic bacteria, may be added to the model biofilm and the influence of disinfectants on these investigated.

A clinically oriented complete denture program for second-year dental students.

The traditional preclinical complete denture prosthodontic curriculum relies predominantly on the laboratory (e.g., bench-type) component of the complete denture fabrication process. In most cases, this involves a passive model of student knowledge acquisition utilizing lectures and low-fidelity laboratory exercises. A recently implemented program in the College of Dentistry at the University of Illinois at Chicago challenges this educational paradigm by introducing an active learning environment for second-year students based on significant clinical exposure with patients. The result is a major shift of emphasis, first, from a purely technical/laboratory aspect of the discipline to patient-centered education and, second, from mastering individual phases of denture fabrication to understanding the entire process of edentulous patient care. To compare student outcomes in the new program with those in the traditional program, their performance overall and in three components of the final examination for each program were statistically compared. The results of the one-way ANOVA analysis show statistically significant improvement in the students' total score in the new program, including their performance on the written, practical, and OSCE portions of the final examination. This article describes the rationale, logistics, challenges, and advantages of the new educational model of the complete denture prosthodontics curriculum.

A model for selection and assessment of community-based sites for dental students' extramural clinical experiences.

As a recipient of the Robert Wood Johnson's Pipeline, Profession, and Practice: Community-Based Dental Education grant, the Extramural Education Program (EEP) at the University of Illinois at Chicago College of Dentistry was charged with developing partnerships with community-based oral health programs throughout Illinois. These programs are to be used for clinical service-learning rotations for fourth-year dental students, relying on the utilization of the dentists employed at the community site as preceptors for the students. Because the College of Dentistry had essentially no community-based service-learning experiences prior to the Robert Wood Johnson grant, procedures and protocols needed to be developed to standardize a process for site and preceptor selection. An administrative process was developed to engage, recruit, and partner with community-based oral health programs that provided direct clinical services. This article will discuss the development of criteria used to select sites and preceptors for extramural clinical rotations; the development of a set of standardized assessment instruments; and the credentialing process for community-based adjunct faculty that leads to the affiliation agreements. These community-based rotations have been integrated into the College of Dentistry curriculum as a required extramural service-learning course referred to as Extramural Clinical Experience (DADM 325).

Analysis of innervation of human mesenteric vessels in non-inflamed and inflamed bowel--a confocal and functional study.

We investigated the distribution and density of perivascular nerves in human mesenteric arteries and veins and their responses to noradrenaline (NA), ATP and neuropeptide Y (NPY) in control (non-inflamed) and inflamed bowel, using confocal microscopy and in vitro pharmacology. The density of innervation at the adventitial-medial border of arteries and within the medial muscle coat of veins was increased in inflammatory bowel disease (IBD). Expression of markers for both sympathetic nerves and sensory-motor nerves was significantly increased in IBD. Calcitonin gene-related peptide-containing sensory-motor nerves were present in control arteries and IBD, but not in control veins. The density of 5-hydroxytryptamine-containing nerves was variable in controls, but consistently increased (three to four times) in IBD. Vasoactive intestinal peptide (VIP) expression increased (doubled) in arteries and veins. Arteries and veins contracted to NA and ATP, but only veins constricted to NPY. ATP contractions were reduced in arteries and veins in IBD, while contractions to NA were only slightly reduced. Neuropeptide Y induced significantly greater (20%) contractions of IBD veins. In summary, the density of sympathetic and sensory-motor innervation of both mesenteric arteries and veins was increased in IBD. Both 5-hydroxytryptamine and VIP immunoreactivity were also increased. The responses of both arteries and veins to ATP, and to a lesser extent NA, were reduced in IBD while responses to NPY were greater in veins. Decreased responses to ATP indicate changes in purinergic-mediated transmission in the pathological state.