关键词： Travel satisfaction   Travel captivity   Mode choice   Travel behavior  

摘要： In this study, we investigated travel captivity from the perspective of travel satisfaction. Using survey data from 565 commuters in Portland, Oregon, we compared satisfaction with the most recent commute trip (using the chosen mode) and hypothetical commute satisfaction if using an alternative mode. The difference in travel satisfaction between the chosen and alternative mode - referred to as the travel satisfaction gap - was used as a fine-grained proxy measure of travel captivity. Results indicate that active mode (walk/bicycle) users would be less satisfied when the alternative modes were auto or transit, while auto and transit commuters would be slightly more satisfied if they commuted by walking or bicycling. These outcomes suggest that auto users are most captive, while active travelers are mostly choice users. Results also show that respondents would be more satisfied with an alternative mode if it would enable more talking to other passengers.

摘要： BACKGROUND Successful airway management is a priority in the resuscitation of critically ill or traumatised patients. Several studies have demonstrated the importance of achieving maximum first pass success, particularly in prehospital advanced airway management. OBJECTIVE To compare success rates of emergency intubations between patients requiring cardiopulmonary resuscitation (CPR) for cardiac arrest (CPR group) and other emergencies (non-CPR group) using the C-MAC PM videolaryngoscope. DESIGN Ongoing analysis of prospective collected prehospital advanced airway management core variables. SETTING Single helicopter emergency medical service (HEMS) 'Christoph 22', Ulm Military Hospital, Germany, May 2009 to July 2018. PATIENTS We included all 1006 HEMS patients on whom prehospital advanced airway management was performed by board-certified anaesthesiologists on call at HEMS 'Christoph 22'. INTERVENTIONS The C-MAC PM was used as the first-line device. The initial direct laryngoscopy was carried out using the C-MAC PM without the monitor in sight. After scoring the direct laryngoscopic view according to the Cormack and Lehane grade, the monitor was folded within the sight of the physician and tracheal intubation was performed using the videolaryngoscopic view without removing the blade. MAIN OUTCOME MEASURES The primary outcome was successful airway management. Secondary outcomes were the patient's position during airway management, necessity for suction, direct and videolaryngoscopic view according to Cormack and Lehane grading, as well as number of attempts needed for successful intubation. RESULTS A patent airway was achieved in all patients including rescue techniques. There was a lower first pass success rate in the CPR group compared with the non-CPR group (84.4 vs. 91.4%, P = 0.01). In the CPR group, direct laryngoscopy resulted more often in a clinically unfavourable (Cormack and Lehane grade 3 or 4) glottic view (CPR vs. non-CPR-group 37.2 vs. 26.7%, P = 0.00

摘要： Calls for curricular reform in medical schools and enhanced integration of basic and clinical science have resulted in a shift toward preclerkship curricula that enhance the clinical relevance of foundational science instruction and provide students with earlier immersion in the clinical environment. These reforms have resulted in shortened preclerkship curricula, yet the promise of integrated basic science education into clerkships has not been sufficiently realized because of barriers such as the nature of clinical practice, time constraints, and limited faculty knowledge. As personalized medicine requires that physicians have a more nuanced understanding of basic science, this is cause for alarm. To address this problem, several schools have developed instructional and assessment strategies to better integrate basic science into the clinical curriculum. In this article, faculty and deans from 11 U.S. medical schools discuss the strategies they implemented and the lessons they learned to provide guidance to other schools seeking to enhance basic science education during clerkships. The strategies include program-level interventions (e.g., longitudinal sessions dedicated to basic science during clerkships, weeks of lessons dedicated to basic science interspersed in clerkships), clerkship-level interventions (e.g., case-based learning with online modules, multidisciplinary clerkship dedicated to applied science), bedside-level interventions (e.g., basic science teaching scripts, self-directed learning), and changes to formative and summative assessments (e.g., spaced repetition/leveraging test-enhanced learning, developing customized examinations). The authors discovered that: interventions were more successful when buy-in from faculty and students was considered, central oversight by curricular committees collaborating with faculty was key, and some integration efforts may require schools to provide significant resources. All schools administered the United States

关键词： alternative promoters   cancer   epigenetics   glioma   glioma stem cells   HOX genes  

摘要： In human, the 39 coding HOX genes and 18 referenced noncoding antisense transcripts are arranged in four genomic clusters named HOXA, B, C, and D. This highly conserved family belongs to the homeobox class of genes that encode transcription factors required for normal development. Therefore, HOX gene deregulation might contribute to the development of many cancer types. Here, we study HOX gene deregulation in adult glioma, a common type of primary brain tumor. We performed extensive molecular analysis of tumor samples, classified according to their isocitrate dehydrogenase (IDH1) gene mutation status, and of glioma stem cells. We found widespread expression of sense and antisense HOX transcripts only in aggressive (IDHwt) glioma samples, although the four HOX clusters displayed DNA hypermethylation. Integrative analysis of expression, DNA methylation, and histone modification signatures along the clusters revealed that HOX gene upregulation relies on canonical and alternative bivalent CpG island promoters that escape hypermethylation. H3K27me3 loss at these promoters emerges as the main cause of widespread HOX gene upregulation in IDHwt glioma cell lines and tumors. Our study provides the first comprehensive description of the epigenetic changes at HOX clusters and their contribution to the transcriptional changes observed in adult glioma. It also identified putative 'master' HOX proteins that might contribute to the tumorigenic potential of glioma stem cells.

关键词： breast cancer   dosing   HER2   modeling   pertuzumab   population pharmacokinetics  

摘要： PERJETA (pertuzumab), administered with Herceptin (trastuzumab), is used in the treatment of human epidermal growth factor receptor 2-positive breast cancer. Pertuzumab is currently approved with an initial loading dose of 840 mg, followed by a 420-mg maintenance dose intravenously every 3 weeks. A reloading dose is required if there is a >= 6-week delay in treatment. In response to the potential treatment disruption due to COVID-19, the impact of dose delays and alternative dosing regimens on intravenous pertuzumab for human epidermal growth factor receptor 2-positive breast cancer treatment is presented. Simulations were conducted by using the validated population pharmacokinetic model for pertuzumab, and included (1) 4-, 6-, and 9-week dose delays of the 840 mg/420 mg every 3 weeks dosing regimen and (2) 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens. Simulations were compared with the currently approved pertuzumab dosing regimen. The simulations in 1000 virtual patients showed that a dose reload (840 mg) is required following a dose delay of >= 6 weeks to maintain comparable C-trough (lowest concentration before the next dose is given) levels to clinical trials. The 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks alternative dosing regimens decrease median steady-state C-trough by approximate to 40% compared with the approved regimen, and <90% of patients will be above the target C-trough. Thus, the alternative 840 mg/420 mg every 4 weeks and 840 mg every 6 weeks pertuzumab dosing regimens are not recommended. Flexibility for intravenous PERJETA-based regimens is available with an alternative route of pertuzumab administration (subcutaneous vs intravenous).

关键词： Karst rocky desertification   Rural energy   Biomass energy   Southwestern China  

摘要： Karst in southwestern China forms a rocky desertification area with a particularly vulnerable ecological environment. Studying the potential of agricultural available biomass energy in this region is of great significance for the construction of the rural energy industry and ecological environment protection in karst mountains. This study investigated three regions with different degrees of rocky desertification in the karst mountains of southwestern China. The characteristics of rural energy consumption and their impact on the ecology of Karst region were analyzed. Moreover, the total available agricultural biomass energy resources in the study area were estimated via residue to product ratio, ecological returning coefficient, collection coefficient, conversion coefficient, and by-product coefficient. The research results indicate that the fragile karst ecological environment and the over-consumption of fuelwood resources are the most important reasons for the evolution of rocky desertification in this region, which exposes karst rocky desertification areas and increases the risk of rocky desertification. Given abundant agricultural biomass energy reserves in karst regions of southwestern China, promoting biomass energy as an alternative for fuelwood carries great significance for ecological protection of karst regions. This can serve as an important measure to promote ecological restoration in karst rocky desertification areas.

关键词： Biomaterials   Orthopaedic   Silicon nitride   Zirconia toughened alumina   Titanium   PEEK  

摘要： A variety of novel biomaterials are emerging as alternatives to conventional metals and alloys, for use in spinal implants. These promise potential advantages with respect to e.g. elastic modulus compatibility with the host bone, improved radiological imaging or enhanced cellular response to facilitate osseointegration. However, to date there is scarce comparative data on the biological response to many of these biomaterials that would give insights into the relative level of bone formation, resorption inhibition and inflammation. Thus, in this study, we aimed to evaluate and compare the in vitro biological response to standard discs of four alternative biomaterials: polyether ether ketone (PEEK), zirconia toughened alumina (ZTA), silicon nitride (SN) and surface-textured silicon nitride (ST-SN), and the reference titanium alloy Ti6Al4V (TI). Material-specific characteristics of these biomaterials were evaluated, such as surface roughness, wettability, protein adsorption (BSA) and apatite forming capacity in simulated body fluid. The activity of pre-osteoblasts seeded on the discs was characterized, by measuring viability, proliferation, attachment and morphology. Then, the osteogenic differentiation of preosteoblasts was compared in vitro from early to late stage by Alizarin Red S staining and real-time PCR analysis. Finally, osteoclast activity and inflammatory response were assessed by real-time PCR analysis. Compared to TI, all other materials generally demonstrated a lower osteoclastic activity and inflammatory response. ZTA and SN showed generally an enhanced osteogenic differentiation and actin length. Overall, we could show that SN and ST-SN showed a higher osteogenic effect than the other reference groups, an inhibitive effect against bone resorption and low inflammation, and the results indicate that silicon nitride has a promising potential to be developed further for spinal implants that require enhanced osseointegration.

关键词： Doravirine   lamivudine   RP‐   HPLC   Tenofovir disoproxil fumarate  

摘要： A novel method was developed for the simultaneous estimation of the doravirine, lamivudine, and tenofovir disoproxil fumarate in the pharmaceutical dosage form. The chromatogram was run through an Ascentis C18 column (150 x 4.6 mm, 2.7 mu m), with the mobile phase consisting of a phosphate buffer and acetonitrile in the ratio of 50:50 (v/v). The mobile phase was pumped through the column at a flow rate of 1 mL/min. The column temperature was maintained at 30 degrees C. The optimized wavelength for doravirine, lamivudine, and tenofovir disoproxil fumarate was 230.0 nm. The retention times for doravirine, lamivudine, and tenofovir disoproxil were 2.222, 2.764, and 3.403 min, respectively;the relative standard deviation (%) values of method precision for doravirine, lamivudine, and tenofovir disoproxil were 0.6, 0.6, and 0.1, respectively. The % recovery was 100.20%, 100.15%, and 100.36% for doravirine, lamivudine, and tenofovir disoproxil fumarate, respectively. The limit of detection and limit of quantification values were obtained from regression equations of doravirine, lamivudine, and tenofovir disoproxil fumarate, and were 0.24 and 0.73 ppm, 0.53 and 1.60 ppm, and 0.47 and 1.43 ppm, respectively. The regression equations of doravirine, lamivudine, and tenofovir disoproxil fumarate were y = 17,541x + 117,303, y = 15,555x + 10,791, and y = 15,250x + 31,663, respectively. The method developed was accurate, simple, precise, sensitive, and economical. Hence, it could be adopted for regular quality control for estimation of doravirine, lamivudine, and tenofovir disoproxil fumarate in pharmaceutical industries.

关键词： Temporomandibular joint   TMJ   ankylosis   mandibulectomy  

摘要： Objectives Temporomandibular joint ankylosis (TMJA) is the partial or complete inability to open the mouth due to intra- or extra-articular fibrous, bony or fibro-osseous tissue proliferation. Surgical procedures such as gap arthroplasty, condylectomy or wide extra-articular osteotomy have been recommended to treat this condition;these techniques are challenging, time-consuming and have been occasionally associated with postoperative recurrence, severe periarticular neurovascular iatrogenic trauma and death. Segmental mandibulectomy had previously been recommended as an alternative option for unilateral TMJA, but the location of mandibulectomy and extent of bone removal from the mandible region have not been mentioned in the literature. This study aimed to validate the area of the mandibular body (rostral, middle or caudal) and amount of bony tissue that should be osteotomized during a segmental mandibulectomy for treatment of unilateral TMJA in cats. Methods In this block study, 30 cadaver heads of domestic shorthair cats were randomly divided into three groups of 10 specimens each based on the mandibular region that would undergo segmental mandibulectomy (rostral, middle and caudal). The size of the removed mandibular segment and pre- and postoperative vertical range of mandibular motion were compared for statistical purposes. Results A significant statistical difference was observed between the pre- and postoperative vertical range of mandibular motion between the rostral, middle and caudal segmental mandibulectomies (P <0.001). The mean postoperative recovered range of mandibular motion for the rostral, middle and caudal segmental mandibulectomies was 50.4%, 81.9% and 90.4%, respectively. Conclusions and relevance The caudal segmental mandibulectomy showed the highest postoperative vertical range of mandibular motion. The removal of a minimum of 1.2 cm of the caudal mandibular body was required to achieve nearly full recovery of presurgical mouth opening in the