Synthesis and Screening of Novel Peptides on Human Pancreatic Islets for Type 1 Diabetes Therapies.

Type 1 diabetic patients characteristically exhibit a loss of insulin production, leading to chronic hyperglycemia and related complications. Herein we describe the design, synthesis and screening of novel oligopeptides for their potential to enhance the secretion of insulin from human pancreatic islets. The investigation of these compounds, based off the patented INGAP-PP sequence, aims to identify the peptide features key to maximizing insulin secretion.Clinical Relevance - This report describes the relative efficacy of selected novel compounds for potential Type 1 Diabetes Therapy. Tested on live human pancreatic islets, the compounds are evaluated for their enhancing/inhibitory effect on the secretion of insulin. These studies pave the way for future targeted drug therapies.

Giant electron-hole transport asymmetry in ultra-short quantum transistors.

Making use of bipolar transport in single-wall carbon nanotube quantum transistors would permit a single device to operate as both a quantum dot and a ballistic conductor or as two quantum dots with different charging energies. Here we report ultra-clean 10 to 100 nm scale suspended nanotube transistors with a large electron-hole transport asymmetry. The devices consist of naked nanotube channels contacted with sections of tube under annealed gold. The annealed gold acts as an n-doping top gate, allowing coherent quantum transport, and can create nanometre-sharp barriers. These tunnel barriers define a single quantum dot whose charging energies to add an electron or a hole are vastly different (e-h charging energy asymmetry). We parameterize the e-h transport asymmetry by the ratio of the hole and electron charging energies ηe-h. This asymmetry is maximized for short channels and small band gap tubes. In a small band gap device, we demonstrate the fabrication of a dual functionality quantum device acting as a quantum dot for holes and a much longer quantum bus for electrons. In a 14 nm-long channel, ηe-h reaches up to 2.6 for a device with a band gap of 270 meV. The charging energies in this device exceed 100 meV.

A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Health system costs for stage-specific breast cancer: a population-based approach.

OBJECTIVE: The objective of the present analysis was to determine the publicly funded health care costs associated with the care of breast cancer (bca) patients by disease stage. METHODS: Incident cases of female invasive bca (2005-2009) were extracted from the Ontario Cancer Registry and linked to administrative datasets from the publicly funded system. The type and use of health care services were stratified by disease stage over the first 2 years after diagnosis. Mean costs and costs by type of clinical resource used in the care of bca patients were compared with costs for a matched control group. The attributable cost for the 2-year time horizon was determined in 2008 Canadian dollars. RESULTS: This cohort study involved 39,655 patients with bca and 190,520 control subjects. The average age in those groups was 61.1 and 60.9 years respectively. Most bca patients were classified as either stage i (34.4%) or stage ii (31.8%). Of the bca cohort, 8% died within the first 2 years after diagnosis. The overall mean cost per bca case from a public payer perspective in the first 2 years after diagnosis was $41,686. Over the 2-year time horizon, the mean cost increased by stage: i, $29,938; ii, $46,893; iii, $65,369; and iv, $66,627. The attributable cost of bca was $31,732. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. CONCLUSIONS: Costs of care increased by stage of bca. Cost drivers were cancer clinic visits, physician billings, and hospitalizations. These data will assist planning and decision-making for the use of limited health care resources.

The role of attentional focus in plyometric training.

AIM: The purpose of this study was to examine how focusing attention during nine weeks of plyometric training influence jumping performance. It was hypothesized that participants utilizing an external focus of attention during practice would produce greater improvements in jumping behavior compared to participants practicing in the internal and control conditions. METHODS: Thirty-six untrained but physically active male college students were randomly assigned to 1 of 3 plyometric groups with a different focus of attention: external (EXF; N.=12), internal (INF; N.=12), and control (CON; N.=12). All participants subsequently participated in the same an 9-week periodized training program. Standing long jump (SLJ), countermovement jump (CMJ) and drop jump (DJ) were tested pre- and posttraining intervention. RESULTS: The EXF group exhibited greater improvement (P<0.05) in jumping distance for SLJ and height for CMJ than both the INF and CON groups, while the enhancement in jumping height for DJ was not superior (P<0.05) in the EXF group in comparison with the INF and CON groups. However, the CON group showed a greater increase (P<0.05) in jumping height for DJ than the INF group. The EXF group increased the range of knee flexion (KF), whereas both the INF and CON groups decreased the KF during the CMJ. Additionally, only the CON group reduced KF during the execution of the DJ. The EXF group (P<0.05) increased contact time, whereas both the INF and CON groups decreased (P<0.05) contact time in DJ. The EXF group had significantly (P<0.05) greater vertical ground reaction force in CMJ and DJ when compared with the INF and CON groups. CONCLUSION: These results suggest that the external focus of attention during plyometric training may provide a greater stimulus to jump performance in slow stretch shortening cycle (SSC) tasks by producing greater force than adopting the internal and no specific focus.

Population-based home care services in breast cancer: utilization and costs.

OBJECTIVE: To determine utilization and costs of home care services (hcs) for individuals with a diagnosis of breast cancer (bc). METHODS: Incident cases of invasive bc in women were extracted from the Ontario Cancer Registry (2005-2009) and linked with other Ontario health care administrative databases. Control patients were selected from the population of women never diagnosed with any type of cancer. The types and proportions of hcs used were determined and stratified by disease stage. Attributable home care utilization and costs for bc patients were determined. Factors associated with hcs costs were assessed using regression analysis. RESULTS: Among the 39,656 bc and 198,280 control patients identified (median age: 61.6 years for both), 75.4% of bc patients used hcs (62.1% stage i; 85.7% stage ii; 94.6% stage iii; 79.1% stage iv) compared with 14.6% of control patients. The number of hcs used per patient-year were significantly higher for the bc patients than for the control patients (14.97 vs. 6.13, p < 0.01), resulting in higher costs per patient-year ($1,210 vs. $325; $885 attributable cost to bc, p < 0.01). The number of hcs utilized and the associated costs increased as the bc stage increased. In contrast, hcs costs decreased as income increased and as previous health care exposure decreased. INTERPRETATION: Patients with bc used twice as many hcs, resulting in costs that were almost 4 times those observed in a matched control group. Less than an additional $1000 per bc patient per year were spent on hcs utilization in the study population.

Telemedicine and telepresence for trauma and emergency care management.

The use of telemedicine is long-standing, but only in recent years has it been applied to the specialities of trauma, emergency care, and surgery. Despite being relatively new, the concept of teletrauma, telepresence, and telesurgery is evolving and is being integrated into modern care of trauma and surgical patients. This paper will address the current applications of telemedicine and telepresence to trauma and emergency care as the new frontiers of telemedicine application. The University Medical Center and the Arizona Telemedicine Program (ATP) in Tucson, Arizona have two functional teletrauma and emergency telemedicine programs and one ad-hoc program, the mobile telemedicine program. The Southern Arizona Telemedicine and Telepresence (SATT) program is an inter-hospital telemedicine program, while the Tucson ER-link is a link between prehospital and emergency room system, and both are built upon a successful existing award winning ATP and the technical infrastructure of the city of Tucson. These two programs represent examples of integrated and collaborative community approaches to solving the lack of trauma and emergency care issue in the region. These networks will not only be used by trauma, but also by all other medical disciplines, and as such have become an example of innovation and dedication to trauma care. The first case of trauma managed over the telemedicine trauma program or "teletrauma" was that of an 18-month-old girl who was the only survival of a car crash with three fatalities. The success of this case and the pilot project of SATT that ensued led to the development of a regional teletrauma program serving close to 1.5 million people. The telepresence of the trauma surgeon, through teletrauma, has infused confidence among local doctors and communities and is being used to identify knowledge gaps of rural health care providers and the needs for instituting new outreach educational programs.

Representing older and disabled people in virtual user trials: data collection methods.

A database was developed to support the creation of a computer-based tool which will support design teams in evaluating the usability of a design during early prototyping and indicate which individuals are effectively excluded or designed out. Methods are described for the collection of multivariate data on 100 real individuals covering a range of physical characteristics and capabilities. These data were tested to ensure a breadth of representation of individuals (particularly older and disabled people) in terms of anthropometry, joint constraints, postural capabilities and task behaviours. The concept of the design tool itself is explored by conducting virtual user trials in the computer-aided design environment. The novel approach of the research encourages empathy with individual users and allows generic abilities, such as bending, reaching and lifting to be assessed.

The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of ropivacaine-induced cardiotoxicity.

BACKGROUND AND OBJECTIVE: The amide-linked local anaesthetics, bupivacaine and ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a previous study, we observed decreased contractility and ST segment depression following ropivacaine administration in anaesthetized dogs. The efficacy of intravenous (i.v.) and intracoronary nicorandil (30 and 100 microg kg(-1)), i.v. nitroglycerin (glyceryl trinitrate) (5 microg kg(-1)) and calcium chloride (1, 2 and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine were studied following the administration of intracoronary ropivacaine. METHODS: Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg kg(-1)). A left-sided thoracotomy was performed and the left circumflex coronary was cannulated. For each dog, the dose of ropivacaine was identified, which produced measurable cardiotoxicity. In each case, ropivacaine was followed by one of the three resuscitation drugs. The effects of each resuscitation drug on ST segments and left ventricular contractility (dP/dt) produced by ropivacaine alone were compared with those produced by ropivacaine followed by each of the three resuscitation drugs using Fisher's exact test. RESULTS: The doses of ropivacaine required to produce depression of left ventricular dP/dt and ST segments ranged from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility (dP/dt) was more rapidly and completely reversed by calcium chloride than by either nitroglycerin or nicorandil (P = 0.008). CONCLUSIONS: Calcium chloride may be effective in the treatment of inadvertent intravascular administration of amide local anaesthetic agents.

The prevalence of musculoskeletal troubles among car drivers.

In order to explore the relationship between car driving and musculoskeletal troubles, a cross-sectional structured-interview survey of low- to high-mileage drivers (including individuals who drove as part of their job) was conducted based on the Nordic Musculoskeletal Questionnaire. The results clearly showed that exposure to car driving was associated with reported sickness absence due to low back trouble and that those who drive as part of their job appear to be more at risk from low back trouble than those whose jobs primarily involve sitting (not driving) and standing activities. The frequency of reported discomfort also increased with higher annual mileage. In addition, drivers of cars with more adjustable driving packages had fewer reported musculoskeletal troubles. This identifies an urgent need for the training of managers of fleet vehicles in the importance of developing measures to reduce this problem, for example, the selection of an individual's car with respect to comfort and postural criteria.

Trauma attending in the resuscitation room: does it affect outcome?

Although there are no Class I data supporting the regionalization of trauma care the consensus is that trauma centers decrease morbidity and mortality. However, the controversy continues over whether trauma surgeons should be in-house or take call from home. The current literature does not answer the question because in all of the recent studies the attendings who took call from home were in the resuscitation room guiding the care. We believe the correct question is: Does the presence of the trauma attending in the resuscitation room make a difference? At a university-affiliated Level II trauma center data from the trauma registry, resuscitation room flowsheet, and dictated admission notes were reviewed on all patients over a 6-month period. Data points were: attending present in the resuscitation room, standard demographics, resuscitation room time, time to operating room (OR), time to CT scan, length of stay, complications, and mortality. A total of 943 patients were studied with 216 (23%) having the attending present in the resuscitation room and 727 (77%) without the attending present. The groups were similar in terms of age, sex, Injury Severity Score, percentage Injury Severity Score greater than 15 (16-17.1%), and mechanism of injury (24-29% penetrating). Of all the data points studied only time to the OR had a statistically significance difference (P < 0.05) with it taking 43.8 minutes (+/-20.1) when the attending was present and 109.4 minutes (+/-107) when the attending was absent. There were also no missed injuries, delays to the OR, or inappropriate workups when the attendings were present. Only the time to the OR reached statistical significance. The time to the OR is indicative of the decision-making process in the resuscitation room, and it is in this area that the attendings' presence is the most useful. Also, we believe that it is important that there were no missed injuries, delays to the OR, or inappropriate workups when the attendings were present in the resuscitation room. This again speaks to the decision-making process. We believe that these data support the need for the attending to be present in the resuscitation room to facilitate accurate and timely decisions regardless of whether they take the call from home or in-house.

Cyanide toxicity in the surgical intensive care unit: a case report.

Hypertension is a widespread entity in the surgical intensive care unit. Not only is the clinical spectrum varied, but the armamentarium available to the clinician is also wide-ranging. Sodium nitroprusside, a potent vasodilator with a short half-life, is often used for hypertensive crisis and to deliberately maintain a low blood in certain clinical conditions. Cyanide toxicity is a known complication of sodium nitroprusside use. Herein is reported a case of probable cyanide toxicity in an elderly trauma patient. The pharmacology of sodium nitroprusside and the pitfalls of making the diagnosis of cyanide toxicity are discussed.

Epidural ropivacaine hydrochloride during labour: protein binding, placental transfer and neonatal outcome.

This study was undertaken: (i) to quantify the effects of labour and epidural analgesia on plasma alpha1-acid glycoprotein concentration, (ii) to examine the effects of changes in plasma alpha1-acid glycoprotein concentration on plasma protein binding and placental transfer of ropivacaine, and (iii) to examine the association between umbilical venous ropivacaine concentration and neurobehavioural function in the neonate. Multiparous patients undergoing induction of labour received a continuous epidural infusion of 0.1% ropivacaine following an epidural bolus. A significant association was demonstrated between maternal plasma alpha1-acid glycoprotein concentration and 1/free fraction of ropivacaine 60 min after starting ropivacaine administration (r(2) = 0.77) but not at delivery. No significant correlation was demonstrable between maternal unbound ropivacaine concentration and either neonatal (cord) ropivacaine concentration or UV/MV (a measure of placental transfer). Thirty minutes after delivery, 9/10 neonates had neurological and adaptive capacity scores < 35, whereas only three infants had scores < 35 at 2 h. All scores exceeded 35 16 h after delivery. No association between mean (SD) umbilical venous ropivacaine concentration [0.09 (0.08) mg x l(-1)] and neurological and adaptive capacity scores was demonstrated.

Functional outcome after open repair of abdominal aortic aneurysm.

INTRODUCTION: Detailed information on functional outcome after open abdominal aortic aneurysm (AAA) repair is sparse. Information about functional outcome of open AAA repair is essential to allow comparison of treatment modalities. METHODS: To determine the functional outcome of patients after open repair of AAA, we reviewed 154 consecutive, nonemergency open repairs of infrarenal AAAs between 1990 and 1997 and each patient's medical records. Clinical variables were recorded for each patient, as were multiple outcomes, including ambulatory status, independent living status, current medical condition, and the patient's perception of recovery and satisfaction. Eighty-seven patients or their families were available for current telephone interview to obtain information about objective functional activities, including walking and driving, and subjective functional information, including assessment of complete recovery and willingness to undergo AAA repair again. Chart data were available for all 154 patients. RESULTS: There were 42 women and 112 men. A total of 139 operations were elective, and 15 were urgent. The operative mortality rate was 4%, mean hospital stay was 10.7 +/- 1.3 days, and mean intensive care unit stay was 4.57 +/- 1.17 days. Seventeen (11%) patients required transfer to a skilled nursing facility with a mean stay of 3.66 +/- 2.9 months. All patients were ambulatory preoperatively, whereas at last follow-up (median, 25 months; range, 0.13-108.5 months), 100 (64%) of the patients remained ambulatory, 34 (22%) required assistance, and 12 (14%) were nonambulatory. At current assessment by telephone interview, 33% of patients described a decrease in their functional activity including driving, shopping, and traveling compared with their preoperative status, whereas 67% were unchanged. When asked to assess their own degree of recovery, 64% of patients stated that they experienced complete recovery with an average time to recovery of 3.9 months, whereas 33% said they had not fully recovered at a mean follow-up of 34 months. Sixteen (18%) patients said they would not undergo AAA repair again knowing the recovery process, even though they appeared to fully understand the implication of AAA rupture. CONCLUSION: Patients undergoing open AAA repair generally experienced significant freedom from surgical complications. However, substantial functional impairment was present. It is unclear whether the functional disability resulted from the AAA surgery or from aging and comorbidities unrelated to surgery.

Relationship between antiphospholipid antibodies and progression of lower extremity arterial occlusive disease after lower extremity bypass operations.

PURPOSE: Antiphospholipid antibodies (APLs), which consist of anticardiolipin antibodies (ACLs) or lupus anticoagulant (LA), are associated with venous thrombosis, stroke, and cardiac events. Although they are present in many patients with lower extremity atherosclerotic occlusive disease (LEAOD), the relationship between APL and the progression of LEAOD has not been reported. A comparison of progression of LEAOD as determined with direct imaging studies in patients with and without APL forms the basis for this report. METHODS: APL+ patients (immunoglobulin M [IgM] or IgA or IgG ACL > 3 SD units above control mean or positive LA) who underwent lower extremity bypass grafting between January 1990 and June 1999 (n = 79) were compared with an APL control group (n = 68). Members of the study and control groups were similar with respect to age, procedure, sex, length of follow-up, and multiple atherosclerosis risk factors. Progression of LEAOD was determined by comparing preoperative arteriograms with postoperative imaging studies (arteriograms or duplex scanning). External iliac, common femoral, superficial femoral and popliteal arteries were graded as < 50% stenosis, > or = 50% stenosis, or occluded. Posterior tibial and anterior tibial arteries were graded as patent or occluded. Progression was defined as any increase in stenosis category. RESULTS: The mean follow-up period was 31 months for APL+ and 35 months for APL- patients (P = not significant). Progression of LEAOD occurred in 58 (73%) of 79 APL+ patients and in 25 (37%) of 68 APL- patients (P <.001). There was no difference in progression in external iliac or common femoral arteries. Differences in progression were noted in more distal arteries; APL+ patients had significantly more progression in superficial femoral (45% vs 16%, P <.01), popliteal (31% vs 12%, P <.01), posterior tibial (29% vs 13%, P <.05), and anterior tibial arteries (29% vs 14%, P <.05). Multivariate logistic regression analysis showed a significant independent association between the presence of APL and progression of LEAOD (P <.0001). CONCLUSION: In this study, the presence of APL in patients undergoing lower extremity bypass operations was a significant independent risk factor for progression of LEAOD. We conclude that this patient group should be closely monitored in the postoperative period and appears ideally suited for prospective studies of therapies to modify LEAOD progression.

Should trauma surgeons render definitive vascular repair in peripheral vascular injuries?

Our hypothesis is that in an established Level I trauma center general trauma surgeons should repair peripheral vascular injuries even in stable patients when there is time for a vascular consult. We reviewed all penetrating peripheral vascular injuries in stable patients operated on by nine experienced general trauma surgeons (1993-1996). Outcome measures were amputation, nerve damage, and vascular complications. There were 43 patients with 44 peripheral vascular injuries identified. Sixty per cent were from stab wounds. There were 27 arterial injuries (carotid four, subclavian one, vertebral two, axillary three, brachial eight, ulnar one, radial two, femoral five, and anterior tibial one). There were three venous injuries (one each subclavian, axillary, and popliteal). There were 14 combined injuries (vertebral two, femoral nine, and popliteal three). There were no mortalities. Morbidity was limited to patients with lower extremity injuries. In the nine patients with combined femoral vessel injury there were three complications (nerve damage, thrombosed arterial repair, and thrombosed venous repair). In the four patients with popliteal venous injuries there were two complications, both venous thrombosis. Our early arterial patency rate was 97.6 per cent. These data support the hypothesis that general surgeons with trauma experience can provide effective treatment of peripheral vascular injuries. The significance of these findings in improving the image of trauma surgery as a career is discussed.

Digital rectal examination for trauma: does every patient need one?

The digital rectal examination is widely accepted as an essential component in the initial assessment of trauma. However, no data have been published that justify its routine use in all seriously injured patients. The objective of this study was to determine what if any impact on subsequent treatment and management decisions the initial digital rectal examination had on injured patients arriving at our emergency department (ED). We conducted a prospective observational study of all injured patients arriving at a Level II trauma center over a period of 6 months. A digital rectal examination was performed on all patients during the secondary survey phase of their initial evaluation shortly after arrival to the ED. The results of the rectal examination were noted for each patient with particular attention placed on the presence or absence of gross blood, Hemoccult result, prostatic examination, rectal vault integrity, and rectal sphincter tone. In addition the patient's hemodynamic parameters while in the ED and the injuries that were sustained were noted, as was their final disposition. Four hundred twenty-three patients were admitted to the ED after sustaining serious injuries. The mean Injury Severity Score was 9.96. The prostatic examination was normal in more than 99 per cent of patients; no high-riding or nonpalpable prostate glands were noted. Twenty-two patients (5.2%) were Hemoccult positive, but in none of these cases did the presence of occult blood in the stool lead to a change in the initial management or diagnostic approach. Three patients (0.7%) with penetrating injuries to the perineal/pelvic area had gross blood on digital rectal examination that prompted operative exploration to rule out a lower gastrointestinal injury. All three had rectal injuries confirmed at surgery. Rectal sphincter tone was normal in 406 (96%) patients, weak in 17 (4%), and absent in none. The only patient in whom the sphincter tone influenced management was an individual complaining of complete paralysis after a blunt mechanism of injury. He had normal rectal sphincter tone and admitted to malingering shortly thereafter. Overall the rectal examination influenced therapeutic decision making in five cases (1.2%). The digital rectal examination is unlikely to affect initial management when applied indiscriminately to all seriously injured patients during the secondary survey. Patients in whom the rectal examination may have a higher probability of influencing management are those with penetrating injuries in proximity to the lower gastrointestinal tract, questionable spinal cord damage, and severe pelvic fractures with potential urethral disruption or open fractures in continuity with the rectal vault. The Hemoccult test does not add useful information and should be discontinued as part of the secondary survey of injured patients.