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Combinatorial nanodot stripe assay to systematically study cell haptotaxis

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microsystems & Nanoengineering 2020年第1期6卷 37-48页

作者： mcolisi Dlamini timothy EKennedy David Juncker Biomedical Engineering Department McGill University3775 University StreetMontrealQC H3A 2B4Canada mcGill Genome Centre 740 Dr.Penfield AvenueMontrealQC H3A 0G1Canada mcGill Program in Neuroengineering MontrealQCCanada Department of Neurology and Neurosurgery McGill University3801 University StreetMontréalQC H3A 2B4Canada

Haptotaxis is critical to cell guidance and development and has been studied in vitro using either gradients or stripe assays that present a binary choice between full and zero coverage of a protein ***,stripes offer only a choice between extremes,while for gradients,cell receptor saturation,migration history,and directional persistence confound the interpretation of cellular ***,we introduce nanodot stripe assays(NSAs)formed by adjacent stripes of nanodot arrays with different surface ***-one pairwise combinations were designed using 0,1,3,10,30,44 and 100%stripes and were patterned with 200×200,400×400 or 800×800 nm 2 *** studied the migration choices of C2C12 myoblasts that express neogenin on NSAs(and three-step gradients)of *** reference surface between the nanodots was backfilled with a mixture of polyethylene glycol and poly-D-lysine to minimize nonspecific cell ***,cell response was independent of nanodot *** to a 0%stripe,cells increasingly chose the high-density stripe with up to~90%of cells on stripes with 10%coverage and *** preference for higher *** netrin-1 coverage was observed only for coverage ratios>2.3,with cell preference plateauing at~80%for ratios≥*** combinatorial NSA enables quantitative studies of cell haptotaxis over the full range of surface coverages and ratios and provides a means to elucidate haptotactic mechanisms.

关键词： filled coverage dot

Aerosol Properties and Their Impacts on Surface CCN at the ARm Southern Great Plains Site during the 2011 midlatitude Continental Convective Clouds Experiment

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Advances in Atmospheric Sciences 2018年第2期35卷 224-233页

作者： timothy LOGAN Xiquan DONG Baike XI Department of Atmospheric Sciences Texas A&M University College Station TX 77843-3150 USA Department of Hydrology andAtmospheric Sciences University of Arizona Tucson AZ 85721-0081 USA

Aerosol particles are of particular importance because of their impacts on cloud development and precipitation processes over land and ocean. Aerosol properties as well as meteorological observations from the Department of Energy Atmospheric Radiation measurement （ARm） platform situated in the Southern Great Plains （SGP） are utilized in this study to illustrate the dependence of continental cloud condensation nuclei （CCN） number concentration （NccN） on aerosol type and transport pathways. ARm-SGP observations from the 2011 midlatitude Continental Convective Clouds Experiment field campaign are presented in this study and compared with our previous work during the 2009-10 Clouds, Aerosol, and Precipitation in the marine Boundary Layer field campaign over the current ARm Eastern North Atlantic site. Northerly winds over the SGP reflect clean, continental conditions with aerosol scattering coefficient （~rsp） values less than 20 mm-1 and Ncct~ values less than 100 cm .3. However, southerly winds over the SGP are responsible for the observed moderate to high correlation （R） among aerosol loading （Crsp 〉 60 mm 1） and NCCN, carbonaceous chemical species （biomass burning smoke）, and precip- itable water vapor. This suggests a common transport mechanism for smoke aerosols and moisture via the Gull＇ of mexico, indicating a strong dependence on air mass type. NASA mERRA-2 reanalysis aerosol and chemical data are moderately to highly correlated with surface ARm-SGP data, suggesting that this facility can represent surface aerosol conditions in the SGE especially during strong aerosol loading events that transport via the Gulf of mexico. Future long-term investigations will help to understand the seasonal influences of air masses on aerosol, CCN, and cloud properties over land in comparison to over ocean.

关键词： aerosol indirect effect aerosol transport biomass burning smoke

Using the win ratio to compare laparoscopic versus open liver resection for colorectal cancer liver metastases

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Hepatobiliary Surgery and Nutrition 2023年第5期12卷 692-703,I0017页

作者： Alessandro Paro J.madison Hyer Brandon S.Avery Diamantis I.Tsilimigras Fabio Bagante Alfredo Guglielmi Andrea Ruzzenente Sorin Alexandrescu George Poultsides Kazunari Sasaki Federico Aucejo timothy m.Pawlik Department of Surgery The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research InstituteColumbusOHUSA University of Verona VeronaItaly Fundeni Clinical Institute BucharestRomania Stanford University StanfordCAUSA Cleveland Clinic Foundation ClevelandOHUSA

Background:We sought to assess the overall benefit of laparoscopic versus open hepatectomy for treatment of colorectal liver metastases(CRLms)using the win ratio,a novel methodological ***:CRLm patients undergoing curative-intent resection in 2001-2018 were identified from an international multi-institutional *** were paired and matched based on age,number and size of lesions,lymph node status and receipt of preoperative *** win ratio was calculated based on margin status,severity of postoperative complications,90-day mortality,time to recurrence,and time to ***:Among 962 patients,the majority underwent open hepatectomy(n=832,86.5%),while a minority underwent laparoscopic hepatectomy(n=130,13.5%).Among matched patient-to-patient pairs,the odds of the patient undergoing laparoscopic resection“winning”were 1.77[WR:1.77,95%confidence interval(CI):1.42-2.34].The win ratio favored laparoscopic hepatectomy independent of low(WR:2.94,95%CI:1.20-6.39),medium(WR:1.56,95%CI:1.16-2.10)or high(WR:7.25,95%CI:1.13-32.0)tumor burden,as well as unilobar(WR:1.71,95%CI:1.25-2.31)or bilobar(WR:4.57,95%CI:2.36-8.64)*** odds of“winning”were particularly pronounced relative to short-term outcomes(i.e.,90-day mortality and severity of postoperative complications)(WR:4.06,95%CI:2.33-7.78).Conclusions:Patients undergoing laparoscopic hepatectomy had 77%increased odds of“winning”.Laparoscopic liver resection should be strongly considered as a preferred approach to resection in CRLm patients.

关键词： Colorectal liver metastases(CRLms) minimally invasive surgery laparoscopic liver resection win ratio

Dietary manipulation and testosterone replacement therapy may explain changes in body composition after spinal cord injury: A retrospective case report

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World Journal of Clinical Cases 2019年第17期7卷 2427-2437页

作者： Ashraf S Gorgey Robert m Lester mina P Ghatas Sakita N Sistrun timothy Lavis Spinal Cord Injury and Disorders Service Hunter Holmes McGuire VAMCRichmondVA 23249United States Department of Physical medicine and Rehabilitation Virginia Commonwealth UniversityRichmondVA 23249United States Bionutrition Service Center for Clinical and Translational ResearchVirginia Commonwealth UniversityRichmondVA 23249United States

BACKGROUND Reduced level of physical activity,high-fat diet and skeletal muscle atrophy are key factors that are likely to contribute to deleterious changes in body composition and metabolic following spinal cord injury (SCI).Reduced caloric intake with lowering percentage macronutrients of fat and increasing protein intake may likely to improve body composition parameters and decrease ectopic adiposity after *** To highlight the effects of dietary manipulation and testosterone replacement therapy (TRT) on body composition after SCI mETHODS A 31-year-old male with T5 SCI was administered transdermal TRT daily for 16 *** intake and percentage macronutrients were analyzed using dietary *** resonance imaging and dual-energy x-ray absorptiometry were used to measure changes in body *** Caloric intake and fat percentage were reduced by 445 kcal/d and 6.5%,*** body weight decreased by 8%,body fat decreased by 29%,and lean mass increased by 7%.Thigh subcutaneous adipose tissue cross-sectional area was reduced by 31%.CONCLUSION manipulation of caloric intake,fat percentage,and protein percentage may have influenced body composition after SCI.

关键词： Spinal cord injury Diet High-protein Low-fat Nutrients Basal metabolic rate Case report

Water balloon-induced orbital fracture in an aviator

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military medical Research 2020年第2期7卷 245-248页

作者： timothy E.Holland David m.Smith Guy N.Gibson Jared G.Brinkerhoff Flight and Operational medical Clinic 78th Medical Group655 Seventh StreetRobins Air Force BaseRobinsGA 31098USA Department of Radiology Ehrling Bergquist Clinic2501 Capehart RdOffutt AFBNEOffutt 68113-2160USA Flight and Operational medical Clinic 5th Medical Group194 Missilie AveMinot AFBNDMinot 58705USA

Background:Orbital fractures are common injuries found in facial *** etiologies of orbital fractures include motor vehicle collisions and *** report the case of a 32-year-old male who suffered an orbital fracture from a water ***,we describe the aeromedical complications that may result from this ***,we attempt to answer the question of when a patient may return to flying after sustaining such an injury through review of the *** presentation:A 32-year-old male pilot with the United States Air Force was at an outdoor event with his unit when he was struck with a water balloon launched from a sling shot into his left *** afterwards,he had an onset of subcutaneous emphysema and was escorted to a nearby Emergency *** tomography identified an orbital fracture with associated orbital and subcutaneous *** patient was evaluated by a plastic surgeon and was determined not to be a surgical *** weeks later,he returned to flying ***:Water balloons are thought to be safe and harmless ***,when coupled with sling shots,water balloons can become formidable projectiles capable of significant orbital injury including orbital *** injuries are concerning to aviators,as the most common sites for fractures of the orbit are the thin ethmoid and maxillary bones adjacent to the *** altitude,gases in the sinuses may expand and enter the orbit through these fractures,which may suddenly incapacitate the *** is important for flight surgeons to identify and assess these individuals to determine suitability for flying.

关键词： Boyle’s law Orbital emphysema Facial fracture

Pharmaceutical salts: Theory, use in solid dosage forms and in situ preparation in an aerosol

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Asian Journal of Pharmaceutical Sciences 2016年第6期11卷 722-734页

作者： timothy Scott Wiedmanna Amir Naqwib Department of Pharmaceutics University of Minnesota308 Harvard St SEMinneapolisMN 55455USA mSP Corporation ShoreviewMN 55126USA

In this article, the theoretical foundation for salts is given with an emphasis on the amount of drug in solution. Consideration is given for the solubility of the non-ionized form, acid dissociation constant and solubility product, which are the limiting constraints. For dissolution of nonionized drugs, the surface pH differs from the bulk pH, giving rise to a lower than expected rate. For salts, theoretical considerations are relatively complex, and an experimental approach to estimating the surface pH is more likely to be of value in predicting the dissolution rate. General guidelines are described for screening, preparing and characterizing drugs as salts, which critically depend on the goal of the product ***, our work involving the preparation of salts as a means to generate aerosols from a solution is provided. The solubility of six structurally related compounds was determined in four acids. Thereafter, the amount of the compound in solution was determined as a function of pH, using the acid that provided the highest solubility. Because the pH required to achieve the needed concentration for aerosol generation was low, ammonia vapor was introduced into the air stream to neutralize aerosol droplets. Solvent was then removed from the aerosol by a silica column. The resulting aerosol had a concentration of 96 μg/l and a mass median particle size of 1.8 μm. The reported pharmacokinetic study substantiated the feasibility of evaluating its safety and efficacy of inhalation administration in the rat model.

关键词： Solubility Salt Aerosol Inhalation Solubility product

Contemporary indications for and outcomes of hepatic resection for neuroendocrine liver metastases

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World Journal of Gastrointestinal Surgery 2020年第4期12卷 159-170页

作者： Steven D Scoville Dimitrios Xourafas Aslam m Ejaz Allan Tsung timothy Pawlik Jordan m Cloyd Department of Surgery Division of Surgical Oncology at The Ohio State UniversityJames Cancer CenterColumbusOH 43210United States The Arthur G James Comprehensive Cancer Center and Solove Research Institute The Ohio State UniversityColumbusOH 43210United States Department of Surgery Harvard Medical SchoolDepartment of SurgeryBrigham and Women's HospitalHarvard Medical SchoolBostonMA 02215United States Department of Surgery The Ohio State UniversityColumbusOH 43210United States Department of Surgery The Ohio State University Wexner Medical CenterColumbusOH 43210United States Department of Surgery Division of Surgical OncologyThe Ohio State University Wexner Medical CenterColumbusOH 43210United States

BACKGROUND Although surgical resection is associated with the best long-term outcomes for neuroendocrine liver metastases(NELm),the current indications for and outcomes of surgery for NELm from a population perspective are not well *** To determine the current indications for and outcomes of liver resection(LR)for NELm using a population-based *** A retrospective review of the 2014-2017 American College of Surgeons National Surgical Quality Improvement Program and targeted hepatectomy databases was performed to identify patients who underwent LR for *** characteristics and 30-d morbidity and mortality were *** Among 669 patients who underwent LR for NELm,the median age was 60(interquartile range:51-67)and 51%were *** the number of metastases resected ranged from 1 to 9,the most common(45%)number of tumors resected was *** majority(68%)of patients had a largest tumor size ofmy(71%)while fewer underwent a right or left hepatectomy or *** majority of operations were open(82%)versus laparoscopic(17%)or robotic(1%).In addition,30%of patients underwent intraoperative ablation while 45%had another concomitant operation including cholecystectomy(28.8%),bowel resection(20.2%),or partial pancreatectomy(3.4%).Overall 30-d morbidity and mortality was 29%and 1.3%,*** multivariate analysis,American Society of Anesthesiologists class≥3[odds ratios(OR),OR=2.089,95%confidence intervals(CI):1.197-3.645],open approach(OR=1.867,95%CI:1.148-3.036),right hepatectomy(OR=1.618,95%CI:1.014-2.582),and prolonged operative time of>230 min(OR=1.731,95%CI:1.168-2.565)were associated with higher 30-d morbidity while intraoperative ablation and concomitant procedures were *** LR for NELm was performed with relatively low postoperative morbidity and *** procedures performed at the time of LR did not increase morbidity.

关键词： Carcinoid Neuroendocrine tumor Primary tumor resection Intraoperative ablation Cholecystectomy Small bowel resection

Joint Contact Forces with Changes in Running Stride Length and midsole Stiffness

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Journal of Science in Sport and Exercise 2020年第1期2卷 69-76页

作者： Joshua m.Thomas WBrent Edwards timothy R.Derrick Department of Health Wellnessand SportUniversity of DubuqueDubuqueIA 52001USA Human Performance Laboratory Faculty of KinesiologyUniversity of CalgaryCalgaryAB T2N 1N4Canada Department of Kinesiology Iowa State University111L Forker BuildingAmesIA 50011USA

The purpose of this study was to determine if lower extremity joint loading was influenced by stride length or shoe midsole *** subjects completed 10 trials of overground running at an average speed of 4.43 m/s in each of three condi-tions:normal running,running with a stride length(SL)reduced by 10%of normal,and running with a cushioned midsole stiffness(i.e.,mechanical impact reduction of 13.7-10.9 g).Reaction forces calculated from inverse dynamics were summed with muscle forces estimated from a musculoskeletal model using static optimization to obtain joint contact forces at the hip,knee and ankle *** components of the contact forces[axial,anterior-posterior,and medial-lateral(mL)]were examined using parametric statistics(α=0.05).Reducing stride length resulted in significant decreases in absolute peak ankle contact forces in the axial direction(normal:-14.5±1.5 BW;reduced SL:-14.0±1.6 BW)and the mL direction(normal:0.67±0.23 BW;reduced SL:0.61±0.21 BW).Reducing stride length also reduced the peak absolute axial forces at the knee(normal:-10.6±1.3 BW;reduced SL:-9.8±1.2 BW)and the hip(normal:-7.26±2.24 BW;reduced SL:-6.75±2.10 BW).The cushioned shoe did not statistically reduce the peak absolute contact forces from the normal stride condition at any of the *** hoc stress analysis suggested that the observed changes in anterior hip force would increase stress more than any of the other statistically significant *** in stride length appear to decrease some joint contact variables but cushioning in the heel region of the shoe does not.

关键词： Gait Injury Compressive force Shear force Cushioning Strain

Neuroendocrine liver metastases: a contemporary review of treatment strategies

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Hepatobiliary Surgery and Nutrition 2020年第4期9卷 440-451页

作者： Jordan m.Cloyd Aslam Ejaz Bhavana Konda mina S.makary timothy m.Pawlik Departments of Surgery The Ohio State UniversityWexner Medical CenterColumbusOHUSA Departments of Internal medicine The Ohio State UniversityWexner Medical CenterColumbusOHUSA Departments of Radiology The Ohio State UniversityWexner Medical CenterColumbusOHUSA

Well-differentiated neuroendocrine tumors(NETs)are globally increasing in prevalence and the liver is the most common site of *** liver metastases(NELm)are heterogeneous in clinical presentation and ***,recent advances in diagnostic techniques and therapeutic strategies have improved the multidisciplinary management of this challenging *** feasible,surgical resection of NELm offers the best long-term *** indications for hepatic resection include performance status acceptable for major liver surgery,grade 1 or 2 tumors,absence of extrahepatic disease,adequate size and function of future liver remnant,and feasibility of resecting>90%of *** therapies including concomitant liver ablation are generally safe when used appropriately and may expand the number of patients eligible for *** patients with synchronous resectable NELm,resection of the primary either in a staged or combined fashion is *** patients who are not surgical candidates,liver-directed therapies such as transarterial embolization,chemoembolization,and radioembolization can provide locoregional control and improve symptoms of carcinoid *** systemic therapy options also exist for patients with advanced or progressive *** research efforts are needed to identify novel biomarkers that will define the optimal indications for and sequencing of treatments to be delivered in a personalized fashion.

关键词： Gastroenteropancreatic neuroendocrine tumors(GEP-NETs) liver-directed therapies carcinoid hepatic resection targeted therapy