Accelerated shifts in terrestrial life zones under rapid climate change.

Rapid climate change is impacting biodiversity, ecosystem function, and human well-being. Though the magnitude and trajectory of climate change are becoming clearer, our understanding of how these changes reshape terrestrial life zones-distinct biogeographic units characterized by biotemperature, precipitation, and aridity representing broad-scale ecosystem types-is limited. To address this gap, we used high-resolution historical climatologies and climate projections to determine the global distribution of historical (1901-1920), contemporary (1979-2013), and future (2061-2080) life zones. Comparing the historical and contemporary distributions shows that changes from one life zone to another during the 20th century impacted 27 million km2 (18.3% of land), with consequences for social and ecological systems. Such changes took place in all biomes, most notably in Boreal Forests, Temperate Coniferous Forests, and Tropical Coniferous Forests. Comparing the contemporary and future life zone distributions shows the pace of life zone changes accelerating rapidly in the 21st century. By 2070, such changes would impact an additional 62 million km2 (42.6% of land) under "business-as-usual" (RCP8.5) emissions scenarios. Accelerated rates of change are observed in hundreds of ecoregions across all biomes except Tropical Coniferous Forests. While only 30 ecoregions (3.5%) had over half of their areas change to a different life zone during the 20th century, by 2070 this number is projected to climb to 111 ecoregions (13.1%) under RCP4.5 and 281 ecoregions (33.2%) under RCP8.5. We identified weak correlations between life zone change and threatened vertebrate richness, levels of vertebrate endemism, cropland extent, and human population densities within ecoregions, illustrating the ubiquitous risks of life zone changes to diverse social-ecological systems. The accelerated pace of life zone changes will increasingly challenge adaptive conservation and sustainable development strategies that incorrectly assume current ecological patterns and livelihood provisioning systems will persist.

Sleep, Psychosocial Functioning, and Device-Specific Adjustment in Patients with Implantable Cardioverter Defibrillators (ICDs).

Rates of sleep disorders and associated adjustment were examined in patients with implantable cardioverter defibrillators (ICDs; n = 42; Mage = 61.57, SD = 12.60). One night of ambulatory polysomnography, 14 days of sleep diaries, and questionnaires (mood, sleepiness, fatigue, device acceptance) were administered. Controlling for ischemia, MANCOVA examined adjustment by sleep diagnosis. Apnea was most common (28.6%), followed by Insomnia (16.7%) and Comorbid Insomnia/Apnea (11.9%). Patients with insomnia reported poorer mood, greater sleepiness, and lower device acceptance than good sleepers; they also demonstrated poorer mood and less ICD device acceptance than patients with sleep apnea. Patients with comorbid insomnia/apnea also exhibited poorer mood and less ICD device acceptance than good sleepers; however, comorbid patients did not significantly differ from insomnia or apnea patients on any measure. Those with disordered sleep (regardless of type) reported greater fatigue than good sleepers. Assessment (and treatment) of difficulties with sleep, mood, fatigue, and device acceptance may be important for the comprehensive clinical management of ICD patients. Further research appears warranted.

Patterns of Behavioral Deficits in Rodents Following Brain Injury Across Species, Gender, and Experimental Model.

Behavioral data were collected from several hundred mice and rats using a variety of experimental models of brain injury. The use of consistent protocols allowed compilation of these data, facilitating analyses of animal behaviors across experimental models, species, and gender. Spatial learning and sensorimotor/coordination data are presented, suggesting that, in general, rats performed better than mice both in the water maze and on the rotarod. Compared with females, males performed slightly better in the water maze and slightly worse on the rotarod. However, gender by species interactions accounted for both of these differences. Male rats performed better in the water maze than female rats, male mice, and female mice, which did not differ. Male mice performed worse on the rotarod than female mice, male rats, and female rats, which performed similarly. Furthermore, animals with subcortical injury were impaired in the water maze, but performed better than animals with cortical injuries. However, only animals with cortical injuries were impaired on the rotarod. Additional covariates, such as edema and lesion size, may further clarify these phenotypes. Overall, we provide evidence that abbreviated test batteries can be specifically designed to test deficits, depending on the species, gender, and model.

The effect of ergonomic laparoscopic tool handle design on performance and efficiency.

BACKGROUND: Many factors can affect a surgeon's performance in the operating room; these may include surgeon comfort, ergonomics of tool handle design, and fatigue. A laparoscopic tool handle designed with ergonomic considerations (pistol grip) was tested against a current market tool with a traditional pinch grip handle. The goal of this study is to quantify the impact ergonomic design considerations which have on surgeon performance. We hypothesized that there will be measurable differences between the efficiency while performing FLS surgical trainer tasks when using both tool handle designs in three categories: time to completion, technical skill, and subjective user ratings. METHODS: The pistol grip incorporates an ergonomic interface intended to reduce contact stress points on the hand and fingers, promote a more neutral operating wrist posture, and reduce hand tremor and fatigue. The traditional pinch grip is a laparoscopic tool developed by Stryker Inc. widely used during minimal invasive surgery. Twenty-three (13 M, 10 F) participants with no existing upper extremity musculoskeletal disorders or experience performing laparoscopic procedures were selected to perform in this study. During a training session prior to testing, participants performed practice trials in a SAGES FLS trainer with both tools. During data collection, participants performed three evaluation tasks using both handle designs (order was randomized, and each trial completed three times). The tasks consisted of FLS peg transfer, cutting, and suturing tasks. RESULTS: Feedback from test participants indicated that they significantly preferred the ergonomic pistol grip in every category (p < 0.05); most notably, participants experienced greater degrees of discomfort in their hands after using the pinch grip tool. Furthermore, participants completed cutting and peg transfer tasks in a shorter time duration (p < 0.05) with the pistol grip than with the pinch grip design; there was no significant difference between completion times for the suturing task. Finally, there was no significant interaction between tool type and errors made during trials. CONCLUSIONS: There was a significant preference for as well as lower pain experienced during use of the pistol grip tool as seen from the survey feedback. Both evaluation tasks (cutting and peg transfer) were also completed significantly faster with the pistol grip tool. Finally, due to the high degree of variability in the error data, it was not possible to draw any meaningful conclusions about the effect of tool design on the number or degree of errors made.

Effect of gastrojejunal feedings on visits and costs in children with neurologic impairment.

OBJECTIVE: The objective of the present study was to determine the effect of gastrojejunal tube (GJT) feedings in children with neurologic impairment (NI) on gastroesophageal reflux disease (GERD)- and/or dysfunctional swallowing-related visits and their associated costs. METHODS: The present study is a retrospective cohort study of children with NI and GERD who underwent GJT placement at the study hospital from December 1999 to October 2006. Visits (emergency department, radiology, and hospitalizations) were reviewed from the time of birth until 1 year following GJT placement and classified as either not GERD and/or dysfunctional swallowing related or GERD and/or dysfunctional swallowing related (eg, pneumonias). Incident rate ratios (IRRs) were calculated by dividing the post-GJT visit rate by the pre-GJT visit rate. Other outcomes included associated costs, fundoplications, and deaths. RESULTS: Thirty-three patients met inclusion criteria. The IRR for total visits was 1.78 (95% confidence interval [CI] 1.12-2.81) and for GERD- and/or dysfunctional swallowing-related visits 2.88 (95% CI 1.68-4.94). Feeding tube-related visits (IRR 5.36, 95% CI 2.73-10.51) accounted for the majority. GERD- and/or dysfunctional swallowing-related costs per child per year were low overall, with no difference from pre-GJT versus post-GJT placement ($1851 vs $4601, P = 0.89). Seven (21%) children underwent Nissen fundoplication and 4 (12%) died within 1 year of GJT placement. Two deaths involved jejunal perforation. CONCLUSIONS: Children with NI and GERD who are treated with GJT feedings have significantly more GERD- and/or dysfunctional swallowing-related visits in the following year. The majority of these visits are because of the procedural complications, which are inexpensive. There is, however, mortality associated with the GJT and some children proceed to a fundoplication.

ICU early physical rehabilitation programs: financial modeling of cost savings.

OBJECTIVE: To evaluate the potential annual net cost savings of implementing an ICU early rehabilitation program. DESIGN: Using data from existing publications and actual experience with an early rehabilitation program in the Johns Hopkins Hospital Medical ICU, we developed a model of net financial savings/costs and presented results for ICUs with 200, 600, 900, and 2,000 annual admissions, accounting for both conservative- and best-case scenarios. Our example scenario provided a projected financial analysis of the Johns Hopkins Medical ICU early rehabilitation program, with 900 admissions per year, using actual reductions in length of stay achieved by this program. SETTING: U.S.-based adult ICUs. INTERVENTIONS: Financial modeling of the introduction of an ICU early rehabilitation program. MEASUREMENTS AND MAIN RESULTS: Net cost savings generated in our example scenario, with 900 annual admissions and actual length of stay reductions of 22% and 19% for the ICU and floor, respectively, were $817,836. Sensitivity analyses, which used conservative- and best-case scenarios for length of stay reductions and varied the per-day ICU and floor costs, across ICUs with 200-2,000 annual admissions, yielded financial projections ranging from -$87,611 (net cost) to $3,763,149 (net savings). Of the 24 scenarios included in these sensitivity analyses, 20 (83%) demonstrated net savings, with a relatively small net cost occurring in the remaining four scenarios, mostly when simultaneously combining the most conservative assumptions. CONCLUSIONS: A financial model, based on actual experience and published data, projects that investment in an ICU early rehabilitation program can generate net financial savings for U.S. hospitals. Even under the most conservative assumptions, the projected net cost of implementing such a program is modest relative to the substantial improvements in patient outcomes demonstrated by ICU early rehabilitation programs.

Managing multiple-casualty incidents: a rural medical preparedness training assessment.

OBJECTIVE: The objectives of this study were to develop a novel training model for using mass-casualty incident (MCI) scenarios that trained hospital and prehospital staff together using Microsoft Visio, images from Google Earth and icons representing first responders, equipment resources, local hospital emergency department bed capacity, and trauma victims. The authors also tested participants' knowledge in the areas of communications, incident command systems (ICS), and triage. METHODS: Participants attended Managing Multiple-Casualty Incidents (MCIs), a one-day training which offered pre- and post-tests, two one-hour functional exercises, and four distinct, one-hour didactic instructional periods. Two MCI functional exercises were conducted. The one-hour trainings focused on communications, National Incident Management Systems/Incident Command Systems (NIMS/ICS) and professional roles and responsibilities in NIMS and triage. The trainings were offered throughout communities in western Montana. First response resource inventories and general manpower statistics for fire, police, Emergency Medical Services (EMS), and emergency department hospital bed capacity were determined prior to MCI scenario construction. A test was given prior to and after the training activities. RESULTS: A total of 175 firefighters, EMS, law enforcement, hospital personnel or other first-responders completed the pre- and post-test. Firefighters produced higher baseline scores than all other disciplines during pre-test analysis. At the end of the training all disciplines demonstrated significantly higher scores on the post-test when compared with their respective baseline averages. Improvements in post-test scores were noted for participants from all disciplines and in all didactic areas: communications, NIMS/ICS, and triage. CONCLUSIONS: Mass-casualty incidents offer significant challenges for prehospital and emergency room workers. Fire, Police and EMS personnel must secure the scene, establish communications, define individuals' roles and responsibilities, allocate resources, triage patients, and assign transport priorities. After emergency department notification and in advance of arrival, emergency department personnel must assess available physical resources and availability and type of manpower, all while managing patients already under their care. Mass-casualty incident trainings should strengthen the key, individual elements essential to well-coordinated response such as communications, incident management system and triage. The practice scenarios should be matched to the specific resources of the community. The authors also believe that these trainings should be provided with all disciplines represented to eliminate training "silos," to allow for discussion of overlapping jurisdictional or organizational responsibilities, and to facilitate team building.

The Tungsten-Promoted Synthesis of Piperidyl-Modified erythro-Methylphenidate Derivatives.

Due to its efficacy as a dopamine receptor agonist, methylphenidate (MPH) is of interest as a potential therapeutic for cocaine addiction. While numerous derivatives of MPH have been investigated for their potential medicinal value, functionalization of the piperidine ring has not been explored. The pyridine borane ligand in WTp(NO)(PMe3)(η2-pyBH3) is dearomatized by the metal and can be elaborated to the analogous η2-mesylpyridinium complex. Installing a methyl phenylacetate moiety at the C2' position via a Reformatsky reaction followed by a tandem protonation/nucleophilic addition sequence results in a library of erythro MPH analogues functionalized at the piperidyl C5' position. The functional group is added chemoselectively to C5', cis to the methyl phenylacetate. Repeating this procedure with an enantioenriched source of the tungsten reagent results in enantioenriched MPH derivatives. All identities of the newly reported compounds are supported by comprehensive 2D NMR and HRMS data or crystallographic data.

Barriers to Online Learning in the Time of COVID-19: A National Survey of Medical Students in the Philippines.

INTRODUCTION: In March 2020, the coronavirus disease 2019 (COVID-19) pandemic forced medical schools in the Philippines to stop face-to-face learning activities and abruptly shift to an online curriculum. This study aimed to identify barriers to online learning from the perspective of medical students in a developing country. METHODS: The authors sent out an electronic survey to medical students in the Philippines from 11 to 24 May 2020. Using a combination of multiple-choice, Likert scale, and open-ended questions, the following data were obtained: demographics, medical school information, access to technological resources, study habits, living conditions, self-assessment of capacity for and perceived barriers to online learning, and proposed interventions. Descriptive statistics were calculated. Responses were compared between student subgroups using nonparametric tests. RESULTS: Among 3670 medical students, 93% owned a smartphone and 83% had a laptop or desktop computer. To access online resources, 79% had a postpaid internet subscription while 19% used prepaid mobile data. Under prevailing conditions, only 1505 students (41%) considered themselves physically and mentally capable of engaging in online learning. Barriers were classified under five categories: technological, individual, domestic, institutional, and community barriers. DISCUSSION: Medical students in the Philippines confronted several interrelated barriers as they tried to adapt to online learning. Most frequently encountered were difficulty adjusting learning styles, having to perform responsibilities at home, and poor communication between educators and learners. By implementing student-centered interventions, medical schools and educators play a significant role in addressing these challenges during the COVID-19 pandemic and beyond. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01231-z.

Charge-based scanning probe readback of nanometer-scale ferroelectric domain patterns at megahertz rates.

We present a method for data storage in continuous ferroelectric (FE) media, applicable to storage systems based on one or more scanning probes. Written FE domains are read back in a destructive fashion by applying a constant voltage of magnitude greater than the coercive voltage, as is done in FE random access memory (FeRAM). The resulting flow of screening charges through the readback amplifier provides sufficient signal to allow readback of domains of minimum dimension of the order of 10 nm at MHz rates, orders of magnitude faster than previously demonstrated techniques for readback of domains in continuous FE media.

Psychology consultation patterns in a medical intensive care unit: A brief report.

PURPOSE/OBJECTIVE: Intensive care unit (ICU) survivors frequently experience long-lasting mental health, cognitive, and physiologic challenges. Psychologists have a role in providing interventions to reduce patient distress during critical illness and improve outcomes. There is limited data regarding psychology consultations in the ICU. This brief report characterizes psychology consultations in a medical intensive care unit (MICU) in an academic medical center. METHOD: Psychology consultations were prospectively tracked, with patient-related data retrospectively collected and analyzed. RESULTS: A total of 79 consecutive psychology consultations occurred at mean of 8 ± 6 days after MICU admission. Reasons for consultation were patient emotional distress (56%), rehabilitation therapy engagement (24%), family engagement (13%), cognitive disturbance (4%), and pain (4%). Patient characteristics were: mean age 56 ± 15 years, 54% women, 53% White, and 34% with psychiatric comorbidity at MICU admission. Patients referred for consultation had a longer MICU length of stay than the total MICU population (12 ± 9 days vs. 4 ± 6 days, p < .01). For consultations for emotional distress compared with limited rehabilitation therapy engagement, patient demographic characteristics were similar, with the exception of women (vs. men) being more commonly consulted for emotional distress (64 vs. 26%, p = .01). CONCLUSIONS: Patients with a longer MICU stay more commonly had a rehabilitation psychology consultation request, typically to provide support for emotional distress or engagement in rehabilitation therapy. Future research should evaluate the effectiveness of psychology interventions in the ICU. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

How to utilize benchmarking in the clinical laboratory.

Benchmarking of clinical laboratory activities has become a tool used increasingly to enable administrators and managers to obtain an independent evaluation of the performance of the laboratory and identify opportunities for improvement. Benchmarking is particularly important because of the diversity and complexity of the various sections of the laboratory. The critical component of laboratory benchmarking is peer comparison, as solutions to shortcomings or problems can be titrated and planned through this process. The reliability of benchmarking must be supplemented and modified by the input of the manager's detailed understanding of local circumstances. At this critical moment, the changes in peer review strategies instituted by JCAHO, CAP, CLIA, and individual states create an urgent opportunity to assist medical directors and laboratory managers in maintaining an overview of the performance and quality of laboratory operations. Unannounced site visits will require prompt reports and alerts of undesirable changes in performance. The future goals of benchmarking must expand to include surveys of laboratory test utilization and patient outcomes as ultimate measures of test utility in the clinical process and important assessments of the quality of patient care.

Measuring Treatment Outcomes in Comorbid Insomnia and Fibromyalgia: Concordance of Subjective and Objective Assessments.

STUDY OBJECTIVES: In insomnia, actigraphy tends to underestimate wake time compared to diaries and PSG. When chronic pain co-occurs with insomnia, sleep may be more fragmented, including more movement and arousals. However, individuals may not be consciously aware of these arousals. We examined the baseline concordance of diaries, actigraphy, and PSG as well as the ability of each assessment method to detect changes in sleep following cognitive behavioral therapy for insomnia (CBT-I). METHODS: Adults with insomnia and fibromyalgia (n = 113) were randomized to CBT-I, CBT for pain, or waitlist control. At baseline and posttreatment, participants completed one night of PSG and two weeks of diaries/actigraphy. RESULTS: At baseline, objective measures estimated lower SOL, higher TST, and higher SE than diaries (ps < 0.05). Compared to PSG, actigraphic estimates were higher for SOL and lower for WASO (ps < 0.05). Repeated measures ANOVAs were conducted for the CBT-I group (n = 15), and significant method by time interactions indicated that the assessment methods differed in their sensitivity to detect treatment-related changes. PSG values did not change significantly for any sleep parameters. However, diaries showed improvements in SOL, WASO, and SE, and actigraphy also detected the WASO and SE improvements (ps < 0.05). CONCLUSIONS: Actigraphy was generally more concordant with PSG than with diaries, which are the recommended assessment for diagnosing insomnia. However, actigraphy showed greater sensitivity to treatment-related changes than PSG; PSG failed to detect any improvements, but actigraphy demonstrated changes in WASO and SE, which were also found with diaries. In comorbid insomnia/fibromyalgia, actigraphy may therefore have utility in measuring treatment outcomes.

Inhibition of cytokine-stimulated thymic lymphocyte proliferation by fatty acids: the role of eicosanoids.

The effect of individual fatty acids on the proliferation of thymic lymphocytes in response to interleukin-1 (IL-1) was investigated. Proliferation was estimated by measuring [3H]thymidine incorporation into the acid insoluble fraction of the thymocytes. A concentration-dependent inhibition (in the range 1-100 microM) in the IL-1-stimulated proliferation was observed with the C20 fatty acids dihomo-gamma-linolenic acid (DGLA), arachidonic acid and eicosapentaenoic acid (EPA). A less pronounced concentration-dependent inhibitory response was observed with the C18 fatty acids linoleic acid, alpha-linolenic acid and gamma-linolenic acid. Palmitic acid and oleic did not have any effect on either basal or IL-1-stimulated proliferation at concentrations up to 100 microM. The potencies of each fatty acid for this effect at a concentration of 100 microM were: arachidonic acid > EPA > or = DGLA > linoleic acid. DGLA, arachidonic acid and EPA also attenuated IL-2-stimulated proliferation. The inhibitory action of these fatty acids was not mediated by conversion to prostaglandins or other eicosanoids as the cyclooxygenase inhibitor, ketoprofen and NDGA did not alter their action. Incubation of thymocytes with radiolabelled DGLA and EPA followed by reverse-phase HPLC analysis revealed that DGLA is predominantly converted to a more polar metabolite which is not PGE1 whereas EPA does not appear to be converted to any other detectable metabolite. The data indicate that the inhibitory actions of fatty acids on cell proliferation do not occur as a result of conversion to other metabolites but may be direct effects. The inhibition of cytokine-stimulated lymphocyte proliferation by unsaturated fatty acids would imply that they may attenuate cell-mediated immune reactions.

Effects of lipid fatty acyl chain structure on the activity of the (Ca2+ + Mg2+)-ATPase.

The (Ca2+ + Mg2+)-ATPase purified from rabbit muscle sarcoplasmic reticulum has been reconstituted into a series of phosphatidylcholines in the liquid crystalline phase. For phosphatidylcholines containing monounsaturated fatty acyl chains, optimal activity is observed for a chain length of C18, with longer or shorter chains supporting lower activities. Phospholipids with methyl-branched chain saturated fatty acids support somewhat lower activities than the corresponding phospholipids with mono-unsaturated fatty acids. Mixed chain phospholipids support ATPase activities comparable to those shown by an unmixed chain phospholipid with the same average chain length. However, the response of the ATPase reconstituted with mixed chain phospholipids to the addition of oleyl alcohol is dominated by the longest fatty acyl chain. Based on their ability to displace brominated phospholipids, relative binding constants to the ATPase of a series of phosphatidylcholines have been determined. Binding to the ATPase is virtually unaffected by fatty acyl chain length or the presence of methyl branches.

Neurosurgical interventions in the treatment of idiopathic Parkinson disease: neurostimulation and neural implantation.

With the exception of thalamotomy for drug-refractory tremor, surgical therapy for Parkinson's disease has been almost abandoned as treatment for Parkinsonian symptoms between 1965 and 1985. Reasons for this development relate to inconsistent postoperative results, complications associated with stereotactic surgical techniques and, most importantly, the advent of levodopa, which is still considered to be the gold standard in pharmacotherapy for Parkinson's disease. However, both, the long-term experience with L-DOPA therapy on the one hand and the progress of advanced stereotactic techniques and fetal graft research on the other hand have lead to reconsideration of surgical therapy in Parkinson's disease for patients, who can not be treated satisfactorily with medication. Both lesions (via thermocoagulation) and/or neurostimulation (via chronic intracerebral implantation of electrodes) in thalamic nuclei (nucleus ventralis oralis posterior/intermedialis thalami; VOP/VIM) may alleviate rest tremor in PD patients. In principle neurostimulation has the significant advantage of reversibility with regard to side effects in comparison to lesion surgery. Furthermore ventro-posterior pallidotomy or chronic stimulation in this structures may ameliorate bradykinesia and levodopa-induced dyskinesias. Additionally, "switching-off" the subthalamic nucleus by neurostimulation has been reported to reduce rigidity, bradykinesia and levodopa-induced ON-OFF-fluctuations. On the other hand, neuronal transplantation of fetal nigral dopamine precursor cells aims at restoring the striatal dopamine deficit. Both animal and clinical experiments have shown that fetal grafts survive intrastriatal transplantation and may ensue moderate to satisfactory improvements, especially in regard to bradykinesia and ON-OFF-fluctuations. Further progress in the field of neuronal transplantation will largely depend on the development of alternative cell resources.

Hirschsprung disease in the premature newborn: a population based study and 40-year single center experience.

BACKGROUND/PURPOSE: Understanding of Hirschsprung disease (HD) in premature newborns (PHD) is anecdotal. We have sought in this study to identify the demographic and clinical features of PHD. METHODS: All patients with HD 1970-2011 treated at our tertiary care children's hospital were identified. Patients with biopsy confirmed HD and EGA <37weeks were selected for further review. Prenatal and birth data, demographics, clinical signs, radiologic and pathologic data, and operative interventions were examined. The occurrence of PHD was observed using data from the Utah Department of Health database 1997-2011. RESULTS: 404 patients with HD from 1970 to 2011 were treated. Twenty-seven (6.7%) had PHD. Mean birth weight in PHD was 2196grams and mean gestational age 34 (range 29-36)weeks. Seven patients had Down syndrome. Nonchromosomal anomalies occurred in 25%. Median time from birth to biopsy diagnosis was 42days (range 2-316days). The most common presenting signs were abdominal distension and bilious emesis. The HD incidence in Utah for all births was 1/4322 (0.023%) and for premature infants 1/3885 (0.027%). CONCLUSIONS: PHD are similar to term infants with HD. Diagnosis of HD is often delayed in premature newborns, and associated anomalies are more common.

Feasibility and safety of in-bed cycling for physical rehabilitation in the intensive care unit.

PURPOSE: The purpose was to evaluate the feasibility and safety of in-bed cycle ergometry as part of routine intensive care unit (ICU) physical therapist (PT) practice. MATERIALS AND METHODS: Between July 1, 2010, and December 31, 2011, we prospectively identified all patients admitted to a 16-bed medical ICU receiving cycling by a PT, prospectively collected data on 12 different potential safety events, and retrospectively conducted a chart review to obtain specific details of each cycling session. RESULTS: Six hundred eighty-eight patients received PT interventions, and 181 (26%) received a total of 541 cycling sessions (median [interquartile range {IQR}] cycling sessions per patient, 2 [1-4]). Patients' mean (SD) age was 57 (17) years, and 103 (57%) were male. The median (IQR) time from medical ICU admission to first PT intervention and first cycling session was 2 (1-4) and 4 (2-6) days, respectively, with a median (IQR) cycling session duration of 25 (18-30) minutes. On cycling days, the proportion of patients receiving mechanical ventilation, vasopressor infusions, and continuous renal replacement therapy was 80%, 8%, and 7%, respectively. A single safety event occurred, yielding a 0.2% event rate (95% upper confidence limit, 1.0%). CONCLUSIONS: Use of in-bed cycling as part of routine PT interventions in ICU patients is feasible and appears safe. Further study of the potential benefits of early in-bed cycling is needed.

Enzymatic mutation detection (EMD) of novel mutations (R565X and R1523X) in the FBN1 gene of patients with Marfan syndrome using T4 endonuclease VII.

The Enzymatic Mutation Detection (EMDtrade mark) method is a streamlined and improved version of the original Enzymatic Cleavage of Mismatch (EMC) method. EMD is a fully homogeneous, rapid four step procedure that allows for detection and localization of mismatched or unmatched nucleotides within heteroduplex DNA. To test the utility of EMD for use in the screening of large and complex genes, the fibrillin 1 (FBN1) gene was scanned in a cohort of six patients diagnosed with connective tissue disorders. Four of the six patients were diagnosed with classic Marfan syndrome (MFS). The results were compared with a previous MDEtrade mark scanning of the same patient cohort. Two causative mutations, R565X and R1523X, were detected by EMD that were not detected by MDE. In both cases, the mutation resulted in premature termination of translation. In addition, several polymorphisms were detected by the enzymatic approach that failed detection by heteroduplex analysis. We propose that the EMD method is a sensitive and rapid approach to mutation detection in large genes such as FBN1.