Search

Precision medicine promises to transform healthcare for groups and individuals through early disease detection, refining diagnoses and tailoring treatments. Analysis of large-scale genomic-phenotypic databases is a critical enabler of precision medicine. Although Asia is home to 60% of the world's population, many Asian ancestries are under-represented in existing databases, leading to missed opportunities for new discoveries, particularly for diseases most relevant for these populations. The Singapore National Precision Medicine initiative is a whole-of-government 10-year initiative aiming to generate precision medicine data of up to one million individuals, integrating genomic, lifestyle, health, social and environmental data. Beyond technologies, routine adoption of precision medicine in clinical practice requires social, ethical, legal and regulatory barriers to be addressed. Identifying driver use cases in which precision medicine results in standardized changes to clinical workflows or improvements in population health, coupled with health economic analysis to demonstrate value-based healthcare, is a vital prerequisite for responsible health system adoption. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) We thank all investigators, staf members and study participants of the contributing cohorts and studies: (1) the HELIOS study at the Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; (2) the GUSTO study jointly hosted by the National University Hospital, KK Women’s and Children’s Hospital, the National University of Singapore and the Singapore Institute for Clinical Sciences, the Agency for Science Technology and Research (A*STAR); (3) the SEED cohort at the Singapore Eye Research Institute; (4) the MEC, National University of Singapore; (5) the PRISM cohort; and (6) the TTSH Personalised Medicine Normal Controls cohort. We also thank the National Supercomputing Centre, Singapore (https://www.ncss.sg) for computation resources. The SG10K_Health project is funded by the Industry Alignment Fund (Pre-Positioning) (IAF-PP, H17/01/a0/007); the project made use of participating study cohorts supported by the following funding sources: (1) the HELIOS study by grants from a Strategic Initiative at Lee Kong Chian School of Medicine, the Singapore MOH under its Singapore Translational Research Investigator Award (NMRC/STaR/0028/2017) and the IAF-PP (H18/01/a0/016); (2) the GUSTO study by the Singapore National Research Foundation under its Translational and Clinical Research Flagship Program and administered by the Singapore MOH’s National Medical Research Council Singapore (NMRC/TCR/004-NUS/2008, NMRC/ TCR/012-NUHS/2014) with additional funding support available through the A*STAR and the IAF-PP (H17/01/a0/005); (3) the SEED study by NMRC/CIRG/1417/2015, NMRC/CIRG/1488/2018 and NMRC/OFLCG/004/2018; (4) the MEC by individual research and clinical scientist award schemes from the Singapore National Medical Research Council (including MOH-000271-00) and the Singapore Biomedical Research Council, the Singapore MOH, the National University of Singapore and the Singapore National University Health System; (5) the PRISM cohort study by NMRC/CG/ M006/2017_NHCS, NMRC/STaR/0011/2012, NMRC/STaR/0026/2015, the Lee Foundation and the Tanoto Foundation; and (6) the TTSH cohort study by NMRC/CG12AUG2017 and CGAug16M012. This research is also supported by the National Research Foundation Singapore under its NPM program Phase II funding (MOH-000588) and administered by the Singapore MOH’s National Medical Research Council.

The current study focuses on the use of outcome framing as a strategic negative message tactic and its impact on partisans. Specifically, this study theorises that the impact of partisan cues such as party affiliation is moderated by differently framed claims in negative political advertising. Participants viewed a negative ad, varying in outcome framing (negative ramifications of electing the targeted candidate versus positive consequences of defeating the target) and partisan matching (in-party versus out-party). Participants were recruited via Amazon’s Mechanical Turk. Experiment 1 ( N = 96), where a Republican candidate was the target of a negative ad, revealed that the persuasiveness of a loss-framed negative ad significantly increased in the out-party versus in-party condition. Experiment 2 ( N = 123), where a Democratic candidate was the target of a negative ad, found that a loss framed-negative ad was significantly more influential than a gain-framed negative ad in both in-party and out-party conditions. Implications exist for design and practice of negative campaign messaging.

This study investigates the use of a commercial-off-the-shelf (COTS) ceramic glow-plug to assist ignition of jet fuel blends with cetane numbers of 30 and 35, below the minimum cetane number of 40 for #2 diesel. Experiments were carried out on a single-cylinder compression-ignition engine operating at 1200 RPM for single and dual-injection (pilot + main) timing sweeps. The COTS glow-plug, termed the ignition assistant, was operated at varying input power levels between 0 and 70 W (stock maximum power input is 30 W) at each SOI. Results demonstrate that the use of an ignition assistant at the higher input powers (50 and 70 W) enables operation over a wider range of SOI timings where more advanced times are limited by high pressure-rise rates and more retarded times are limited by rapidly increasing coefficient of variation of gross indicated mean effective pressure. Use of the ignition assistant enables stable combustion at later injection timings increasing the operable range of SOI timings. For the CN 30 fuel, at earlier injection timings, pressure traces, and heat release analysis demonstrated the advancement of start of combustion and combustion phasing with the ignition assistant on. At retarded injection timings where combustion would not otherwise occur completely for the CN 30 fuel, operating the ignition assistant at the higher powers enabled combustion phasing to be advanced and combustion to be stabilized at conditions where, with the ignition assistant off, misfire (flameout) would occur. Furthermore, the ignition assistant enabled combustion phasing to follow an approximately linear response with respect to SOI timing over a wider range of SOI times.

Objective This study aimed to evaluate the effects of a financial literacy curriculum on resident and fellow's sense of well-being and financial stress. Study Design This single institution pilot study prospectively enrolled obstetrician/gynecologist (OB/GYN) medical trainees (residents and fellows) to take part in a five-part personal financial literacy curriculum during the 2019 to 2020 academic year. Topics covered included the following: financial education and its relationship to personal well-being, overview of financial terms and principles, budgeting, debt planning, and investing and giving. Primary outcomes were the improvement in well-being as measured by the Expanded Well-Being Index (E-WBI) and financial stress as measured by the Financial Stress Scale-College Version (FSS-CV) survey. Results Of the 35 residents and fellows who participated in the study, 21 (60%) completed the postintervention survey. After course completion, there was significant improvement in the individual's E-WBI (p Conclusion Cultivating financial literacy is associated with an improvement in the sense of well-being in residents and fellows and should be considered for inclusion in other graduate medical education (GME) programs.

PDF file - 43K

PDF file - 81K, Supplementary Table 2 Primers and probe sets utilized in this study were designed by the Primer Express 1.5 software and synthesized by Sigma-Aldrich. These primers and probes were utilized for quantitative PCR in ancillary biologic studies, and the data

PDF file - 106K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

Purpose: Ad5.SSTR/TK.RGD is an infectivity-enhanced adenovirus expressing a therapeutic thymidine kinase suicide gene and a somatostatin receptor (SSTR) that allows for noninvasive gene transfer imaging. The purpose of this study was to identify the maximum tolerated dose (MTD), toxicities, clinical efficacy, and biologic effects of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer.Experimental Design: Eligible patients were treated intraperitoneally for 3 days with 1 × 109 to 1 × 1012 vp/dose of Ad5.SSTR/TK.RGD followed by intravenous ganciclovir for 14 days. Toxicity and clinical efficacy were assessed using Common Toxicity Criteria (CTC) Adverse Events grading and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Imaging using In-111 pentetreotide was obtained before and after treatment. Tissue samples were obtained to evaluate for gene transfer, generation of wild-type virus, viral shedding, and antibody response.Results: Twelve patients were treated in three cohorts. The most common vector-related clinical toxicities were grade I/II constitutional or pain symptoms, experienced most often in patients treated at the highest dose. MTD was not identified. Five patients showed stable disease; all others experienced progressive disease. One patient with stable disease experienced complete resolution of disease and normalization of CA125 on further follow-up. Imaging detected increased In-111 pentetreotide retention in patients treated at the highest dose. Ancillary studies showed presence of Ad5.SSTR/TK.RGD virus and HSV1-tk expression in ascites samples collected at various time points in most patients treated within the higher dose cohorts.Conclusions: This study shows the safety, potential efficacy, and possible gene transfer imaging capacity of Ad5.SSTR/TK.RGD in patients with recurrent gynecologic cancer. Further development of this novel gene therapeutic appears to be warranted. Clin Cancer Res; 18(12); 3440–51. ©2012 AACR.

PDF file - 51K, Patients were then assigned into one of three Ad5.SSTR/TK.RGD dose cohorts ranging from 1 x 109 vp/d to 1 x 1012 vp/d (6 x 107 pfu/d to 6 x 1010 pfu/d). This dose administration strategy has been validated in our preclinical studies; assigned Ad5.SSTR/TK

Herein, we studied the impact of empty LNP (eLNP), component of mRNA-based vaccine, on anti-viral pathways and immune function of cells from young and aged individuals. eLNP induced maturation of monocyte derived dendritic cells (MDDCs). We further show that eLNP upregulated CD40 and induced cytokine production in multiple DC subsets and monocytes. This coincided with phosphorylation of TANK binding kinase 1 (pTBK1) and interferon response factor 7 (pIRF7). In response to eLNP, healthy older adults (>65 yrs) have decreased CD40 expression, and IFN-γ output compared to young adults (

IntroductionDespite improvement in progression-free survival with poly (ADP-ribose) polymerase inhibitors (PARPi) as maintenance therapy for ovarian cancer, many patients will eventually progress on therapy. Oligoprogression is uniquely suited to considerations of local consolidation therapy in this setting, but not commonly used in ovarian cancer. In this study we evaluated the proportion of patients on PARPi maintenance who developed limited sites of disease, the location of progression, and their natural history.MethodsFrom January 2006 to December 2020, natural language processing software (DEEP6AI) was used to identify 58 patients with ovarian cancer treated with PARPi maintenance after complete or partial response after surgery and platinum-based chemotherapy at our institution. Patients were assessed for presence and location of recurrence based on radiologic findings.ResultsThe median patient age was 65 (IQR 57–71) years. Patients had a median of two lines of chemotherapy prior to starting PARPi. With a median follow-up of 48 (range 12–149) months, 32 (55%) patients had a recurrence on maintenance olaparib and 11 (34%) patients developed oligoprogression (≤3 sites). For the 11 patients with oligoprogression, three patients developed recurrence in one site, five in two sites, and three in three sites. The sites of oligoprogression were pelvic/periaortic nodal (27%), peritoneal (27%), liver (27%), lung/mediastinal (14%), and brain (5%). The median progression-free survival for the entire cohort was 6.0 months (95% CI 4.2 to 7.8); median overall survival was not met. There were no significant differences in overall survival (p=0.81) or progression-free survival (p=0.95) between patients with and without oligoprogression.ConclusionsOne-third of patients on PARPi maintenance experienced oligoprogression defined as limited to ≤3 sites. These patients may benefit from local consolidation therapy. A larger dataset is needed to validate these findings to assess if trials investigating local therapy for these patients is of value.

Anti-Asian violence increased during the COVID-19 pandemic. Asian American/Pacific Islanders (AAPI) represent a diverse population experiencing a long history of stereotyping and exclusionism; however, this group is often left out of diversity/inclusion conversations. In academic medicine, AAPI are under-represented in leadership. We characterized the personal/professional experiences of AAPI gynecologic oncology trainees and assessed the impact of a virtual panel discussion with leaders in the field.An anonymous survey was disseminated online to trainees in/interested in gynecologic oncology fellowship who identified as AAPI, using modified snowball sampling. A virtual session with AAPI leaders in gynecologic oncology discussed themes emerging from survey responses. Session attendees completed an anonymous follow-up survey. Results were assessed quantitatively and qualitatively.44/59 (75%) respondents participated in the pre-survey; 23 (39%) participated in the virtual session. All session participants (23/23, 100%) completed the post-session survey. Participants reported increased identity-related thoughts with the COVID-19 pandemic (88% during, 61% prior). Sixty-eight percent reported that identity-related thoughts/awareness changed during the pandemic. Presence of AAPI colleagues was associated with higher perceived identity-related support from their department. Of those without AAPI coworkers, none (0%) felt 'moderately' or 'extremely well supported.' Qualitative analysis demonstrated that the panel discussion created a sense of community and encouragement, combating previously reported isolation and self-consciousness. Participants reported more connection with their heritage and identified more personal/professional topics that might be related to their cultural backgrounds.This intervention demonstrates the opportunity to provide a supportive network for mentorship and professional development in a culturally inclusive way.

A group of experts from different disciplines was convened to develop guidelines for the management of upper visual field impairments related to eyelid ptosis and dermatochalasis. The goal was to provide evidence-based recommendations to improve patient care.A multidisciplinary group of experts representing their specialty organizations was selected. A systematic literature review was performed including topics regarding documentation of the underlying cause for visual field impairment, selection of an appropriate surgical repair, assessment of the type of anesthesia, the use of adjunctive brow procedures, and follow-up assessments. The Grading of Recommendations, Assessment, Development, and Evaluation methodology process was used to evaluate the relevant studies. Clinical practice recommendations were developed using BRIDGE-Wiz (Building Recommendations In a Developers' Guideline Editor) software.Each topic area was assessed. A clinical recommendation was made, and the relevant literature was discussed.The review of the literature revealed varied complication rates and diverse treatment modalities for the correction of upper visual field deficit. Strong recommendations could not be made in most topic areas because of a paucity of methodologically sound studies in the literature. More rigorously designed studies are needed to measure outcomes of interest, with fewer sources of potential error or bias.Therapeutic, V.

Purpose This study aims to examine how the relative importance of a search versus a credence attribute, strategically addressed in a flu vaccination advertisement, varies as a function of message sidedness. A search attribute was designed to highlight the affordability of flu shots, and a credence attribute addressed the potential health benefits of flu vaccination. Design/methodology/approach Two experiments were designed to explore how the relative persuasiveness of search versus credence attributes varies as a function of message sidedness in the context of flu vaccination advertising. In Experiment 1, the search–credence attribute type was manipulated by addressing either the affordability (e.g. “Get free flu shots”) or indirect health benefits of flu vaccines (e.g. “Improve herd immunity/community health”). In Experiment 2, an individual-level credence attribute (e.g. “Strengthen your immune system”) was created and compared to the other two attribute conditions used in Experiment 1: a search versus a societal credence versus an individual credence attribute. Findings Experiment 1 (N = 114) revealed the relative advantage of a search attribute (free flu shots) in the two-sided persuasion. Experiment 2 (N = 193) indicated that the persuasive impact of a societal credence attribute (herd immunity/community health) was greater in the two-sided message condition (vs one-sided message condition). Originality/value Relatively little research has examined how consumers respond to strategic flu prevention and vaccination messages promoting either credence or search attributes. Motivated by the need to investigate the relative effectiveness of stressing “herd immunity” versus “free flu shots” in flu vaccination advertising, this study examines how the effects of these distinct attributes on flu vaccination judgments differ between two-sided (e.g. “No vaccine is 100% effective”) and one-sided persuasion.

OBJECTIVES: Poly(ADP-ribose) polymerase (PARP) inhibitors are expensive and their use is expanding. We aimed to evaluate cost sharing patterns between patients, payors, and financial assistance programs. METHODS: We identified ovarian cancer patients prescribed a PARP inhibitor from 5/2015–9/2019 using our pharmacy database. Cost information was collected for patients who filled their prescription at our specialty pharmacy. We calculated descriptive statistics for monthly PARP inhibitor costs for patients, payors, and financial assistance programs. We used Wilcoxon rank sum tests to evaluate monthly costs based on insurance characteristics. RESULTS: Seventy-six patients filled 94 different PARP inhibitor prescriptions with 42 (45%) prescriptions obtained using any type of financial assistance program. We analyzed 232 prescription months for the 41 prescriptions with available cost data. This included 18 (44%) prescriptions for rucaparib, 18 (44%) for niraparib, and 5 (12%) for olaparib. The total monthly drug cost was average $12,422 and median $13,700. The monthly out-of-pocket (OOP) cost for patients was average $46 and median $0 (IQR $0–4). Payors had the highest monthly costs with average $12,019 and median $13,662 (IQR $9,914–14,709). Financial assistance programs contributed average $358 and median $0 per month (IQR $0–150). Patients with public (p

Fuel-flexible aircraft propulsion systems using compression ignition engines will require novel strategies for reducing the ignition delay of low-reactivity fuels to feasible timescales. Hot surface ignition of fuel sprays has been implemented in some practical situations, but the complex nature of flame formation within the spray structure poses significant challenges. In order to design next-generation ignition devices, the capacity of hot surface heating elements to promote fuel spray ignition must be investigated. In this study, a rapid compression machine (RCM) was used to examine the ignition process of a single kerosene-based F-24 jet fuel spray with a cylindrical heating element inserted into the spray periphery. The experiments, performed with moderately high injection pressures of 40 MPa, have demonstrated two modes of ignition governed by surface temperature and insertion depth of the heating element. There exists an optimal position where the heating element tip is located in the fuel vapor cone around the liquid spray. For this configuration, a critical surface temperature was identified (∼1250 K), above which short ignition delays associated with a “spray ignition” mode are consistently achieved. In this case, a local ignition flame kernel propagates downstream to the flame lift-off length before full ignition of the spray. In comparison, below the critical temperature a slower “volumetric” mode results. The extended ignition delays associated with this mode may be impractical for compression ignition engines operating at high speeds and increased altitude.

Background In order to correct upper lid laxity, upper blepharoplasty, subbrow excision, and forehead lift have been utilized. Our newly developed subbrow excision attaches the orbicularis oculi muscle to the frontalis muscle. This improves the longevity of the result without inhibiting the gliding plane of the periorbita. Method From January 2016 to July 2018, 564 patients were operated on using this technique. Among them, 41 were male and 523 were female with the average age of 59.5 years. The average size of the subbrow excision was 55 mm × 8 mm. From the upper skin incision site, the upper dissection proceeded cephalad in the subcutaneous plane just above the orbicularis oculi muscle to the point where the frontalis muscle was seen. The lower flap was created by incising the orbicularis oculi muscle 5 mm cephalad to the distal skin incision. From this 5-mm orbicularis muscle stump, the dissection proceeded caudally in a plane between the orbicularis muscle and the orbital septum. Once this flap was created, the 5-mm muscle stump was attached to the exposed frontalis muscle in a horizontal mattress fashion in three areas. The skin incision was then closed. Three months after the operation, a satisfaction survey was conducted using the Likert scale. Results The patients were followed postoperatively for at least 6 months. In all but two cases, the orbital laxity improved. However, in the brow’s lateral third where the frontalis muscle does not exist, a slight lowering of the brow had occurred. The incision healed well without any keloid or hypertrophic scars. There were no significant complications such as superior orbital nerve entrapment-related sensory problems. Conclusions Subbrow lift utilizing the frontalis muscle attachment to the lower flap orbicularis muscle is a novel method of correcting upper eyelid skin hooding. The technique does not rely on periosteal fixation. Therefore, the eyebrow gliding plane is not violated. Thus, the natural eyebrow movement is maintained. There were no cases of injury to the deep branch of the supraorbital nerve, poor wound healing, or other significant complications. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

A new multi-location soot sampling method is used to enhance the knowledge about the structural evolution of in-flame particles in a light-duty optical diesel engine. Through thermophoresis-based particle sampling performed at multiple in-bowl locations, the soot structures are shown for both early formation stage and later stage from the same combustion event. Three different jet-spacing angles of 45°, 90° and 180° were studied to analyse how different levels of jet–jet interaction impact the soot particle morphology and internal structure. One selected jet–jet interaction condition was further analysed to show differences in soot structures between the up-swirl side and down-swirl side of the wall jets. From transmission electron microscopes (TEM) images of the sampled soot particles and their statistical size analysis, it was found soot particles initially formed within 45∘ separated jet–jet interaction region have un-solidified premature aggregates due to limited carbonisation in the locally fuel-rich mixtures. When these soot particles travelled on the down-swirl side of the jets, they became solidified and carbonised while the oxidation was evident from the smaller soot primary particle and longer carbon-layer fringe and lower tortuosity. The higher mixing on the up-swirl side of the jets further enhanced the soot oxidation, resulting in even smaller soot primary particle, fragmentation of large soot aggregates, and even longer and less curved carbon-layer fringes. Regarding jet–jet interaction, the 180° jet spacing angle created no jet–jet interaction condition on the soot sampler locations. For smaller jet-spacing angles, the increase in jet–jet interaction promoted the soot formation as evidenced by larger and more complex soot aggregates formed due to more active soot aggregation and agglomeration. The soot oxidation became limited at higher jet–jet interaction conditions, which led to more amorphous soot internal structures.

Objectives Trainee well-being is a core component of ACGME program requirements and the SGO has recognized the high incidence of burnout among gynecologic oncologists and its negative impact. To foster a culture of wellness throughout the SGO community we sought to engage current fellows along with fellowship directors in a structured didactic program designed to teach wellness. We evaluated the feasibility of and preliminary responses to a pilot curriculum designed to teach skills that promote wellness and prevent burnout. Methods The SGO Wellness Taskforce developed a curriculum with topics based on established evidence as well as specialty specific stressors such as end of life discussions. Faculty leaders from 15 pilot-sites attended a full-day training course and then taught four modules over four months. Interactive modules engaged fellows through reflective writing, guided discussion, and multimedia presentations. Fellows completed the Perceived Stress Scale pre- and post-implementation and provided feedback regarding attitudes toward wellness and the individual modules. Faculty curriculum leaders completed surveys regarding their attitudes toward the curriculum as well as their trainees' reactions. Results Among 73 participating gynecologic oncology fellows, 95% (69/73) and 52/73 (71%) completed the pre-and post-surveys, respectively. Only 34/73 (49%) respondents reported that there was wellness programming at their institution prior to the initiation of the SGO curriculum. At institutions where such programming was available, 35% (12/34) reported not utilizing them. Fifty-five (80%) fellows had PSS scores greater than 12 compared to 39 (75%) post-intervention. After the curriculum, the percentage of fellows comfortable discussing wellness topics increased from 63 to 74%. Prior to the curriculum, 75% felt they could identify symptoms of burnout or psychosocial distress. This increased to 90% post-intervention. The modules were well received by fellows, and the time spent addressing wellness was widely appreciated. Conclusions A structured curriculum to promote wellness among gynecologic oncology fellows is feasible and was associated with observed decreased reported stress among fellows at participating programs. This curriculum addresses ACGME requirements regarding trainee well-being, and showed potential for more programmatic, nationwide implementation. Fellowship culture change was not directly measured, but may have been one of the most significant positive outcomes of the wellness program. Further longitudinal studies will be necessary to understand the natural course of fellow burnout and the impact of structured wellness programming.

Hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin when used at the time of interval cytoreductive surgery (ICS) after neoadjuvant chemotherapy (NACT) has been shown to provide a survival advantage compared to interval cytoreduction alone for patients with advanced epithelial ovarian cancer in a cost-effective manner. A recent large multi-center retrospective cohort study showed a survival advantage with HIPEC given during primary debulking surgery compared to surgery alone. While there is an ongoing randomized controlled trial examining HIPEC at the time of primary cytoreductive surgery (PCS) before chemotherapy (OVHIPEC-2), there is currently no study of this practice in the United States or cost data to inform incorporation of this practice. To help guide the use of HIPEC in the upfront setting until the results of the OVHIPEC-2 are available in 2026, a decision-analytic cost-effectiveness model of the US healthcare sector was developed for patients undergoing PCS with or without HIPEC. Effectiveness inputs were extracted from a Chinese retrospective cohort study of 425 patients who underwent PCS with HIPEC and 159 patients who underwent PCS alone. We found incremental cost effectiveness ratios (ICER) of $9,789 per life year saved (LYS) for optimal PCS, $18,164/LYS for suboptimal PCS, and $7,854/LYS for all patients. Our findings provide preliminary data to support that HIPEC at the time of primary cytoreductive surgery can be considered cost-effective regardless of residual disease status when using a standard willingness to pay threshold.

Energy addition using a hot surface probe is required for reliable ignition of aircraft compression ignition engines running on fuel variations and at altitude conditions. Thus, durability of the hot surface probe is crucial for application in these engines. Thermo-mechanical stress is one of the key parameters that determine durability, which requires an accurate prediction of the transient temperature field based on well-defined boundary conditions representing the dynamic and complex fluid flow inside engines. To meet this requirement, the present study focuses on transient thermo-mechanical stress analysis using a sequentially coupled CFD-FEA approach to understand transient thermo-mechanical responses of the hot surface probe. A 3D transient reacting flow simulation was conducted first using CONVERGE software, the results of which were exported to map thermal and pressure boundary conditions onto a structural finite element mesh. Transient thermo-mechanical stress analysis was performed sequentially using ABAQUS software utilizing the mapped boundary conditions. The results such as transient temperature history, resultant thermo- mechanical stress, displacement, potential failure modes, etc. were critically reviewed, which can provide helpful information for further design improvement.

Diesel engines equipped with ignition assist devices such as glow plugs may improve combustion behavior at low temperatures and with low cetane fuels found in remote fields. The coordination of injection timing and the energy input of the ignition assist needs to continuously adjust to maintain the best combustion phasing at all conditions. However, most diesel engines do not use closed-loop combustion control and operate in a sub-optimal manner because the dispersion of combustion phasing, also known as cycle-to-cycle variability, requires careful feedback controller design. This work presents an initial investigation of a control-oriented model that captures the average and statistical influence of commercial glow plugs used for ignition assist beyond the start-up phase. Experiments were conducted at a single speed and load operating point as a proof of concept to obtain a model that quantifies the combustion phasing statistics and thus can guide feedback control design. The developed phenomenological model includes the engine’s thermal state because it impacts combustion behavior over the course of repeated experiments. The 3-term mean phasing model and 2-term standard deviation model estimate start of combustion within 0.6 and 0.2 crank angle degrees, respectively, and can be readily expanded to more operating conditions.

This study shows the in-cylinder soot reduction mechanism associated with injection timing variation in a small-bore optical diesel engine. For the three selected injection timings, three optical-/laser-based imaging diagnostics were performed to show the development of high-temperature reaction and soot within the cylinder, which include OH* chemiluminescence, planar laser–induced fluorescence of hydroxyl and planar laser–induced incandescence. In addition, detailed soot morphology analysis was conducted using thermophoresis-based soot particle sampling from two locations within the piston bowl, and the subsequent analysis of transmission electron microscope (TEM) images of the sampled soot aggregates was also conducted. The results suggest that when fuel injection timing is varied, ambient gas temperature makes a predominant effect on soot formation and oxidation. This is primarily combustion phasing effect as the advanced fuel injection moved the start of combustion closer to the top dead centre, and therefore, soot formation and oxidation occurred at elevated ambient gas temperature. There was an overall development pattern of in-cylinder soot consistently found for three injection timings of this study. The planar laser–induced incandescence images showed that a few small soot pockets first appear around the jet axis, which promptly grow into large soot regions behind the head of the flame marked planar laser–induced fluorescence of hydroxyl. The soot signals disappear due to significant oxidation induced by surrounding OH radicals. When the injection timing is advanced, the soot formation becomes higher as indicated by higher total laser–induced incandescence coverage, increased sampled particle counts and larger and more stretched soot aggregate structures. However, soot oxidation is also enhanced under this elevated ambient temperature environment. At the most advanced injection timing of this study, the enhanced soot oxidation outperformed the increased soot formation with both peak laser–induced incandescence signal coverage and late-cycle coverage showing lower values than those of more retarded injection timings.

This study shows how soot particles inside the cylinder of the engine are reduced due to high pressure fuel injection used in a light-duty single-cylinder optical diesel engine fuelled with methyl decanoate, a selected surrogate fuel for the diagnostics. For various injection pressures, planar laser induced incandescence (PLII) imaging and planar laser-induced fluorescence of hydroxyl (OH-PLIF) imaging were performed to understand the temporal and spatial development of soot and high-temperature flames. In addition, a thermophoresis-based particle sampling technique was used to obtain transmission electron microscope (TEM) images of soot aggregates and primary particles for detailed morphology analysis. The OH-PLIF images suggest that an increase in the injection pressure leads to wider distribution of high-temperature flames likely due to better mixing. The enhanced high-temperature reaction can promote soot formation evidenced by both a faster increase of LII signals and larger soot aggregates on the TEM images. However, the increased OH radicals at higher injection pressure accelerates the soot oxidation as shown in a higher decreasing rate of LII signals as well as dramatic reduction of the sampled soot aggregates at later crank angles. The analysis of nanoscale carbon layer fringe structures also shows a consistent trend that, at higher injection pressure, the soot particles are more oxidized to form more graphitic carbon layer structures. Therefore, it is concluded that the in-cylinder soot reduction at higher injection pressure conditions is due to enhanced soot oxidation despite increased soot formation.

The sandfish, Holothuria (Metriatyla) scabra Jaeger, 1833 is a commercially-valuable tropical sea cucumber species which is overexploited throughout much of its distributional range, the Philippine archipelago included. The need for management interventions to sustain the fishery is recognized. However, the lack of knowledge on the genetic structure of natural populations needs to be addressed to guide management initiatives. The present study examined genetic diversity and spatial patterns of genetic structure of sandfish populations across the Philippine archipelago. Population genetic analysis using 11 microsatellite markers revealed weak yet significant regional genetic structure among 15 H. scabra populations across the Philippine archipelago (FST = 0.016; P 0.05). Peripheral locations exhibited limited gene flow (Philippine Sea, South China Sea, Sulu Sea and Celebes Sea; mean FST = 0.023, P

This study shows how the structure of soot particles within the flame changes due to the relative direction of the swirl flow in a small-bore diesel engine in which significant flame–wall interactions cause about half of the flame travelling against the swirl flow while the other half penetrating in the same direction. The thermophoresis-based particle sampling method was used to collect soot from three different in-flame locations including the flame–wall impingement point near the jet axis and the two 60° off-axis locations on the up-swirl and down-swirl side of the wall-interacting jet. The sampled soot particle images were obtained using transmission electron microscopes and the image post-processing was conducted for statistical analysis of size distribution of soot primary particles and aggregates, fractal dimension, and sub-nanoscale parameters such as the carbon layer fringe length, tortuosity, and spacing. The results show that the jet-wall impingement region is dominated by many small immature particles with amorphous internal structure, which is very different to large, fractal-like soot aggregates sampled from 60° downstream location on the down-swirl side. This structure variation suggests that the small immature particles underwent surface growth, coagulation and aggregation as they travelled along the piston-bowl wall. During this soot growth, the particle internal structure exhibits the transformation from amorphous carbon segments to a typical core–shell structure. Compared to those on the down-swirl side, the soot particles sampled on the up-swirl side show much lower number counts and more compact aggregates composed of highly concentrated primary particles. This soot aggregate structure, together with much narrower carbon layer gap, indicates higher level of soot oxidation on the up-swirl side of the jet.

We report the sequencing and detection of 36 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage in the Philippines.

We report the sequencing and detection of 39 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) samples containing lineage-defining mutations specific to viruses belonging to the B.1.1.7 lineage (UK variant) in the Philippines.

The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.351 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

Additional file 1. Figure S1: Testing the learning ability of MT CNN using differentlengths of k mers. Table S1: Transformation of percentage of assigned reads to discretevariables for the naive Bayesian network. Table S2: The insertion, deletion, and mismatch rates for simulating50 mers using Mason2.

Objective Common robotic training curricula in the US entail completion of an online module followed by lab training with standardized exercises, such as manipulating needles with robotic needle drivers. Assessments are generally limited to elapsed time and subjective proficiency. We sought to test the feasibility of a simulation-based robotic hysterectomy curriculum to collect objective measurements of trainee progress, map the trainee learning curve and provide a system for trainee-specific evaluation. Methods An observational cohort study of a single institutions' residency members participating in a procedural hysterectomy simulation performed every 4 months. Each simulation episode had one-on-one teaching. The robotic platform was used to measure all movements within cartesian coordinates, the number of clutches, instrument collisions, time to complete the simulated hysterectomy, and unintended injuries during the procedure. Results Voluntary participation was high. Objective metrics were successfully recorded at each session and improved nearly universally. More senior residents demonstrated superior capabilities compared to junior residents as expected. The majority of residents (29/31) were able to complete an entire simulated hysterectomy in the allotted 30-minute training session period by the end of the year. Conclusions This program establishes learning curves based on objective data points using a risk-free simulation platform. The curves can then be used to evaluate trainee skill level and tailor teaching to specific objective competencies. The pilot curriculum can be tailored to the unique needs of each surgical discipline's residency training.

e17526 Background: Adenocarcinoma and adenosquamous carcinoma of the cervix are subtypes of HPV related cervical cancer. As virally mediated tumors, they have become an obvious choice for immunotherapy treatment approach. Currently, there is little information about the presence of immunological tumor markers among patients with endocervical adenocarcinomas. We hypothesized cervical adenocarcinomas highly express immunotherapy markers. Here we characterize the protein status of immunotherapy markers in a large single institution dataset. Methods: An IRB approved retrospective review of cervical adenocarcinoma and adenosquamous carcinoma was performed. We gathered original slides for each patient and performed immunohistochemistry (IHC) for tumor markers CD8, PDL1, TIM3 and LAG3. Demographic and pathologic data was captured. Patients were categorized by positivity percentage for each marker. Descriptive statistics and univariate analysis were used. Results: A total of 97 patients met criteria for the study and slides were available for staining in 68 patients. Demographic data showed a median age of 42 years old with majority of patients identifying as White at 66%, followed by Hispanic (13%), Asian (10%), other (7%) and Black (1%). Of the entire cohort, 75% were adenocarcinoma, 25% were adenosquamous carcinoma. Among those with recorded status, 82% were HPV positive, 14% had metastasis, and 13% had recurrence. On univariate analysis, adenocarcinoma was significantly more common in patients who were LAG3 < 1% or PDL < 1% (p = 0.002, p = 0.007). Patients who were LAG3 < 1% or PDL < 1% were also less likely to have Grade 1 tumors (p = 0.006, 0.03). When analyzing by respective immune marker percentage group there were no statistically significant differences in LVSI, depth of invasion, stage, or recurrence rate. By IHC, 68% were PDL1 > 1% positive, 63% were LAG3 > 1% positive, 100% were TIM3 > 1% positive, 100% were CD8 > 1% positive. Seven of the 68 patients had a recurrence. Of those patients with recurrence, one was treated with immunotherapy. Conclusions: A large proportion of cervical adenocarcinomas displayed immunotherapy targets by IHC suggesting that combined immunotherapy agents may be useful in this population. Further study is needed to assess whether IHC is predictive of outcome or response.[Table: see text]

Study Objective Determine near-optimal dose, safety, and efficacy of nerindocianine in pelvic ureter detection with near-infrared fluorescence imaging in women undergoing minimally invasive pelvic surgery with 3 Food and Drug Administration–cleared imaging systems. Design Open label, phase 1/2a study. Setting University of Alabama at Birmingham. Patients Forty-one female subjects undergoing minimally invasive gynecologic surgery. Interventions Subjects received a single dose of nerindocianine sodium, starting at 0.06-mg/kg body weight and increased/decreased until the near-optimal dose was determined (part A). Examine the degree of concordance between endoscopic and robotic devices (part B). Measurements and Main Results In part A, composite scores were collected every 10 minutes for 30 minutes and then every 15 minutes through 90 minutes using a scale measuring the anatomy/laterality of ureter visualization. In part B (paired imaging system efficacy), 2 cohorts of 8 subjects each received the near-optimal dose. Composite scores for visualization of the ureter were collected at 10 and 30 minutes postinfusion with the Firefly Imaging System and either the PINPOINT or 1588 AIM endoscope. Composite scores were compared to examine the degree of concordance between devices. Part A comprised 25 total subjects enrolled in dosing groups 1, 2, and 3 (0.06-, 0.12-, and 0.045-mg/kg, respectively). Median time to first ureter visualization was 10 minutes (all groups). The nerindocianine 0.06-mg/kg and 0.12-mg/kg groups had longer length of time of visualization than the 0.045-mg/kg group, resulting in the selection of 0.06 mg/kg as the near-optimal dose. Part B enrolled 16 total subjects in 2 groups dosed at 0.06 mg/kg. Efficacy analysis showed no statistically significant difference in composite scores with Firefly versus PINPOINT or 1588 AIM. Conclusion Nerindocianine was well tolerated with visualization of the ureter demonstrated in 88.9% of the subjects through 90 minutes postdosing. No meaningful visualization differences were observed among the Food and Drug Administration–cleared surgical imaging systems used.