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1.
Plast Reconstr Surg Glob Open ; 12(8): e6030, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39114802

ABSTRACT

Background: A previous study by the authors noted a decline in independent plastic surgery residency programs and rising applicant participation. This study provides updates on match trends and influential predictors, and gathers program leaders' views on the future of the independent track. Methods: Match data (2019-2022) were obtained from the San Francisco match after American Council of Educators in Plastic Surgery approval. Variables influencing match success were analyzed, and program leaders were surveyed about desirable applicant traits and program trajectories. Results: From 2019 to 2022, 243 of 428 applicants matched. Programs and positions declined by 10% and 9.5%, respectively. Applicants rose to 42.3%, but match rates fell from 82% to 56%. Osteopathic graduates doubled, whereas international graduates increased to 53.8%. Successful matches were associated with US allopathic medical school graduates, university-affiliated general surgery residencies, eight or more interviews, United States Medical Licensing Examination scores greater than 230, and high post graduate year (PGY)1-3 American Board of Surgery In-service Training Examination scores (PGY1-64.7%, PGY2-61.2%, PGY3-60.7%; P < 0.05). Of surveyed programs, 55.6% aimed to continue running the independent track in the next year. Conversely, 7.4% planned to discontinue in the next year, 22.2% within 2-5 years, 7.4% within the next decade, and 7.4% were unsure. Conclusions: Although support for the independent plastic surgery track remains, program participation diminishes as applicant interest increases, intensifying match challenges. Increasing number of interviews improves match potential. Program leaders display varied commitments, with looming plans for some programs to discontinue offering this track. Applicant evaluation pivots on strong recommendations, research, and test scores.

2.
Mol Neurodegener ; 19(1): 59, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090623

ABSTRACT

BACKGROUND: Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson's Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. METHODS: In a case-control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer's disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. RESULTS: The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. CONCLUSIONS AND RELEVANCE: Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.


Subject(s)
Leukocytes, Mononuclear , Lewy Body Disease , Parkinson Disease , Humans , Parkinson Disease/immunology , Parkinson Disease/metabolism , Lewy Body Disease/immunology , Male , Female , Aged , Case-Control Studies , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Biomarkers/metabolism , Middle Aged , Cohort Studies , Aged, 80 and over , Lewy Bodies/pathology , Lewy Bodies/metabolism , Single-Cell Analysis/methods
4.
JACC Heart Fail ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39093259

ABSTRACT

BACKGROUND: Heart transplantation following donation after circulatory death (DCD HT) has short-term survival outcomes comparable to donation after brain death and has led to a significant increase in transplantation volume. The U.S. experience with the normothermic regional perfusion (NRP) DCD HT procurement method has not been evaluated. OBJECTIVES: The aim of this study was to examine short-term outcomes associated with NRP vs direct procurement and perfusion (DPP) methods used during DCD HT in the United States. METHODS: The UNOS (United Network for Organ Sharing) registry was queried for all adult (age ≥18 years) heart recipients and corresponding donors of controlled DCD HT from January 2019-December 2023. Transplantations were stratified by NRP or DPP reperfusion methods. The primary outcome was overall survival. RESULTS: A total of 918 heart donors and recipients met inclusion criteria, including 622 (68%) DPP and 296 (32%) NRP transplantations. Unadjusted Kaplan-Meier survival analysis demonstrated improved short-term survival associated with NRP (log-rank P = 0.005). After adjustment, DCD HT with NRP was independently associated with improved survival (HR: 0.39 [95% CI: 0.22-0.70]; P = 0.002). A propensity-matched analysis similarly demonstrated a cumulative survival benefit to NRP (log-rank P = 0.006). CONCLUSIONS: In this largest national series of DCD HT procurement perfusion strategies, NRP is associated with improved short-term survival as compared with DPP. This study evaluates the U.S. early experience with DCD HT, and longer-term follow-up data are needed to further assess the impact of DPP and NRP methods on post-heart transplantation outcomes.

5.
mBio ; : e0139224, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39105596

ABSTRACT

Mechanistic understanding of interactions in many host-microbe systems, including the honey bee microbiome, is limited by a lack of easy-to-use genome engineering approaches. To this end, we demonstrate a one-step genome engineering approach for making gene deletions and insertions in the chromosomes of honey bee gut bacterial symbionts. Electroporation of linear or non-replicating plasmid DNA containing an antibiotic resistance cassette flanked by regions with homology to a symbiont genome reliably results in chromosomal integration. This lightweight approach does not require expressing any exogenous recombination machinery. The high concentrations of large DNAs with long homology regions needed to make the process efficient can be readily produced using modern DNA synthesis and assembly methods. We use this approach to knock out genes, including genes involved in biofilm formation, and insert fluorescent protein genes into the chromosome of the betaproteobacterial bee gut symbiont Snodgrassella alvi. We are also able to engineer the genomes of multiple strains of S. alvi and another species, Snodgrassella communis, which is found in the bumble bee gut microbiome. Finally, we use the same method to engineer the chromosome of another bee symbiont, Bartonella apis, which is an alphaproteobacterium. As expected, gene knockout in S. alvi using this approach is recA-dependent, suggesting that this straightforward procedure can be applied to other microbes that lack convenient genome engineering methods. IMPORTANCE: Honey bees are ecologically and economically important crop pollinators with bacterial gut symbionts that influence their health. Microbiome-based strategies for studying or improving bee health have utilized wild-type or plasmid-engineered bacteria. We demonstrate that a straightforward, single-step method can be used to insert cassettes and replace genes in the chromosomes of multiple bee gut bacteria. This method can be used for investigating the mechanisms of host-microbe interactions in the bee gut community and stably engineering symbionts that benefit pollinator health.

6.
JAMA Netw Open ; 7(8): e2425373, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39093561

ABSTRACT

Importance: Artificial intelligence (AI) has permeated academia, especially OpenAI Chat Generative Pretrained Transformer (ChatGPT), a large language model. However, little has been reported on its use in medical research. Objective: To assess a chatbot's capability to generate and grade medical research abstracts. Design, Setting, and Participants: In this cross-sectional study, ChatGPT versions 3.5 and 4.0 (referred to as chatbot 1 and chatbot 2) were coached to generate 10 abstracts by providing background literature, prompts, analyzed data for each topic, and 10 previously presented, unassociated abstracts to serve as models. The study was conducted between August 2023 and February 2024 (including data analysis). Exposure: Abstract versions utilizing the same topic and data were written by a surgical trainee or a senior physician or generated by chatbot 1 and chatbot 2 for comparison. The 10 training abstracts were written by 8 surgical residents or fellows, edited by the same senior surgeon, at a high-volume hospital in the Southeastern US with an emphasis on outcomes-based research. Abstract comparison was then based on 10 abstracts written by 5 surgical trainees within the first 6 months of their research year, edited by the same senior author. Main Outcomes and Measures: The primary outcome measurements were the abstract grades using 10- and 20-point scales and ranks (first to fourth). Abstract versions by chatbot 1, chatbot 2, junior residents, and the senior author were compared and judged by blinded surgeon-reviewers as well as both chatbot models. Five academic attending surgeons from Denmark, the UK, and the US, with extensive experience in surgical organizations, research, and abstract evaluation served as reviewers. Results: Surgeon-reviewers were unable to differentiate between abstract versions. Each reviewer ranked an AI-generated version first at least once. Abstracts demonstrated no difference in their median (IQR) 10-point scores (resident, 7.0 [6.0-8.0]; senior author, 7.0 [6.0-8.0]; chatbot 1, 7.0 [6.0-8.0]; chatbot 2, 7.0 [6.0-8.0]; P = .61), 20-point scores (resident, 14.0 [12.0-7.0]; senior author, 15.0 [13.0-17.0]; chatbot 1, 14.0 [12.0-16.0]; chatbot 2, 14.0 [13.0-16.0]; P = .50), or rank (resident, 3.0 [1.0-4.0]; senior author, 2.0 [1.0-4.0]; chatbot 1, 3.0 [2.0-4.0]; chatbot 2, 2.0 [1.0-3.0]; P = .14). The abstract grades given by chatbot 1 were comparable to the surgeon-reviewers' grades. However, chatbot 2 graded more favorably than the surgeon-reviewers and chatbot 1. Median (IQR) chatbot 2-reviewer grades were higher than surgeon-reviewer grades of all 4 abstract versions (resident, 14.0 [12.0-17.0] vs 16.9 [16.0-17.5]; P = .02; senior author, 15.0 [13.0-17.0] vs 17.0 [16.5-18.0]; P = .03; chatbot 1, 14.0 [12.0-16.0] vs 17.8 [17.5-18.5]; P = .002; chatbot 2, 14.0 [13.0-16.0] vs 16.8 [14.5-18.0]; P = .04). When comparing the grades of the 2 chatbots, chatbot 2 gave higher median (IQR) grades for abstracts than chatbot 1 (resident, 14.0 [13.0-15.0] vs 16.9 [16.0-17.5]; P = .003; senior author, 13.5 [13.0-15.5] vs 17.0 [16.5-18.0]; P = .004; chatbot 1, 14.5 [13.0-15.0] vs 17.8 [17.5-18.5]; P = .003; chatbot 2, 14.0 [13.0-15.0] vs 16.8 [14.5-18.0]; P = .01). Conclusions and Relevance: In this cross-sectional study, trained chatbots generated convincing medical abstracts, undifferentiable from resident or senior author drafts. Chatbot 1 graded abstracts similarly to surgeon-reviewers, while chatbot 2 was less stringent. These findings may assist surgeon-scientists in successfully implementing AI in medical research.


Subject(s)
Abstracting and Indexing , Biomedical Research , Humans , Cross-Sectional Studies , Artificial Intelligence , Surgeons , Internship and Residency/statistics & numerical data , General Surgery/education
7.
Blood ; 144(5): 471-472, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39088225

Subject(s)
Humans
8.
Clin Cancer Res ; 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39078289

ABSTRACT

PURPOSE: Cytarabine (also known as ara-C) has been the backbone of acute myeloid leukemia (AML) chemotherapy for over five decades. Recent pharmacogenomics-based 10-SNP ara-C score (ACS10) showed low ACS10 (£0) to be associated with poor outcome in AML patients treated with standard chemotherapy. Here, we evaluated ACS10 score in the context of three different induction 1 regimens in pediatric AML patients. EXPERIMENTAL DESIGN: ACS10 score groups (low,£0 or high,>0) were evaluated for association with event-free survival (EFS) and overall survival (OS) by three randomized treatment arms in patients treated on the AML02 (NCT00136084) and AML08 (NCT00703820) clinical trials: AML02 low-dose cytarabine (LDAC arm, n=91), AML02+AML08 high-dose cytarabine (HDAC arm, n=194) and AML08 clofarabine+ cytarabine (Clo/Ara-C arm, n=105) induction 1 regimens. RESULTS: Within the low-ACS10 score (£0) group, significantly improved EFS and OS was observed among patients treated with Clo/Ara-C as compared to LDAC (EFS, HR=0.45, 95% CI, 0.23-0.88, p=0.020; OS, HR=0.44, 95% CI, 0.19-0.99, p=0.048). In contrast, within the high-ACS10 score group (score >0) augmentation with Clo/Ara-C was not favorable as compared to LDAC (Clo/Ara-C vs. LDAC, EFS, HR=1.95, 95% CI: 1.05-3.63, p=0.035; OS HR=2.17, 95%CI: 1.05-4.49; p=0.037). Personalization models predicted 9% improvement in outcome in ACS10 score-based tailored induction (Clo/Ara-C for low and LDAC for high-ACS10 groups) as compared to non-personalized approaches (p<0.002). CONCLUSIONS: Our findings suggest that tailoring induction regimens using ACS10 scores can significantly improve outcome in patients with AML. Given the SNPs are germline, preemptive genotyping can accelerate matching the most effective remission induction regimen.

9.
Microorganisms ; 12(7)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-39065067

ABSTRACT

We used inter-delta typing (IDT) and MALDI-TOF profiling to characterize the genetic and phenotypic diversity of 45 commercially available winemaking Saccharomyces cerevisiae strains and 60 isolates from an organic winemaker from Waipara, New Zealand, as a stratified approach for predicting the commercial potential of indigenous isolates. A total of 35 IDTs were identified from the commercial strains, with another 17 novel types defined among the Waipara isolates. IDT 3 was a common type among strains associated with champagne production, and the only type in commercial strains also observed in indigenous isolates. MALDI-TOF MS also demonstrated its potential in S. cerevisiae typing, particularly when the high-mass region (m/z 2000-20,000) was used, with most indigenous strains from each of two fermentation systems distinguished. Furthermore, the comparison between commercial strains and indigenous isolates assigned to IDT 3 revealed a correlation between the low-mass data (m/z 500-4000) analysis and the recommended use of commercial winemaking strains. Both IDT and MALDI-TOF analyses offer useful insights into the genotypic and phenotypic diversity of S. cerevisiae, with MALDI-TOF offering potential advantages for the prediction of applications for novel, locally isolated strains that may be valuable for product development and diversification.

10.
Nat Commun ; 15(1): 6242, 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39048554

ABSTRACT

Engineered DNA will slow the growth of a host cell if it redirects limiting resources or otherwise interferes with homeostasis. Escape mutants that alleviate this burden can rapidly evolve and take over cell populations, making genetic engineering less reliable and predictable. Synthetic biologists often use genetic parts encoded on plasmids, but their burden is rarely characterized. We measured how 301 BioBrick plasmids affected Escherichia coli growth and found that 59 (19.6%) were burdensome, primarily because they depleted the limited gene expression resources of host cells. Overall, no BioBricks reduced the growth rate of E. coli by >45%, which agreed with a population genetic model that predicts such plasmids should be unclonable. We made this model available online for education ( https://barricklab.org/burden-model ) and added our burden measurements to the iGEM Registry. Our results establish a fundamental limit on what DNA constructs and genetic modifications can be successfully engineered into cells.


Subject(s)
Escherichia coli , Genetic Engineering , Plasmids , Synthetic Biology , Synthetic Biology/methods , Escherichia coli/genetics , Escherichia coli/metabolism , Plasmids/genetics , Genetic Engineering/methods , Models, Genetic
11.
Burns ; 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-39043513

ABSTRACT

BACKGROUND: A phase 3b, open-label, multicenter, expanded-access study (NCT04123548) evaluated safety and clinical outcomes of StrataGraft treatment in adults with deep partial-thickness thermal burns with intact dermal elements. METHODS: Adult patients with 3 % to < 50 % total body surface area burns were treated with a single application of ≤ 1:1 meshed StrataGraft and followed for 24 weeks. Primary endpoint was count and percentage of patients with treatment-emergent adverse events (TEAEs). Secondary endpoints included confirmed wound closure (WC) at Week 12, durable WC at Week 24, time to WC, scar evaluation, and wound infection-related events. RESULTS: Fifty-two patients with 96 treatment sites were enrolled. Pruritus was the most common TEAE (22 patients [42.3 %]). Twenty serious TEAEs occurred in 10 patients (19.2 %); none were related to StrataGraft. There were 4 (7.7 %) deaths (aspiration, myocardial infarction, self-injury, Gram-negative rod sepsis); none were related to StrataGraft. Confirmed WC was achieved by Week 12 in 33 patients (63.5 %; 95 % CI: 50.4-76.5 %) and 69 treatment sites (71.9 %; 95 % CI: 62.9-80.9 %). Durable WC was achieved by Week 24 in 29 patients (55.8 %; 95 % CI: 42.3-69.3 %) and 58 treatment sites (60.4 %; 95 % CI: 50.6-70.2 %). CONCLUSIONS: StrataGraft demonstrated clinical benefit. Safety data were consistent with previously reported findings.

12.
Chem Rev ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39018111

ABSTRACT

Making a measurement over millions of nanoparticles or exposed crystal facets seldom reports on reactivity of a single nanoparticle or facet, which may depart drastically from ensemble measurements. Within the past 30 years, science has moved toward studying the reactivity of single atoms, molecules, and nanoparticles, one at a time. This shift has been fueled by the realization that everything changes at the nanoscale, especially important industrially relevant properties like those important to electrocatalysis. Studying single nanoscale entities, however, is not trivial and has required the development of new measurement tools. This review explores a tale of the clever use of old and new measurement tools to study electrocatalysis at the single entity level. We explore in detail the complex interrelationship between measurement method, electrocatalytic material, and reaction of interest (e.g., carbon dioxide reduction, oxygen reduction, hydrazine oxidation, etc.). We end with our perspective on the future of single entity electrocatalysis with a key focus on what types of measurements present the greatest opportunity for fundamental discovery.

13.
Plast Reconstr Surg Glob Open ; 12(7): e5938, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38957722

ABSTRACT

Background: Skeletal muscle relaxants have emerged as a broad category of analgesic adjuncts, aiming to improve pain relief and reduce opioid reliance. These drugs induce muscle relaxation and reduce muscle spasms, and therefore, they are commonly used in surgical procedures involving muscle manipulation, such as abdominal surgery, breast surgery, and spine surgery. However, their analgesic efficacy and opioid-sparing effects are poorly explored. Methods: A scoping review of literature was performed with several electronic databases. We used a search string with a sequence of text words and word variants related to central muscle relaxants, pain management, postoperative pain, and specific muscle relaxants. Results: Review of literature shows significant heterogeneity among the studies in terms of surgical procedures, patient populations, choice of muscle relaxant, and timing and duration of administration, potentially limiting the generalizability of the findings and the ability for pooled analysis. Conclusions: Given the lack of evidence, we recommend that the use of skeletal muscle relaxants be reserved for patients in whom an optimal multimodal analgesic technique is not adequate. Also, there may be a limited role for these drugs in patients at high risk of postoperative pain undergoing surgical procedures with expected high opioid requirements. Due to the concerns of potential adverse effects, the decision to use muscle relaxants in vulnerable populations should be made carefully, weighing the benefits against the risks.

14.
Healthcare (Basel) ; 12(13)2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38998867

ABSTRACT

(1) Background: Body dysmorphic disorder (BDD) presents significant challenges in aesthetic and reconstructive plastic surgery, impacting patient outcomes and well-being. Understanding its prevalence and associated factors is crucial for effective patient care. (2) Methods: A systematic review of national and international databases on body dysmorphic disorder, plastic surgery, cosmetic surgery, reconstructive surgery, and prevalence yielded 999 studies between 1878 and April 2024. Inclusion criteria focused on studies reporting prevalence while excluding those with small sample sizes (<20 participants), unclear diagnostic criteria for BDD, and non-English accessibility. (3) Results: A meta-analysis using a random effects model was conducted on 65 studies involving 17,107 patients to estimate the prevalence of BDD. The overall estimated prevalence of BDD was 18.6%; 10,776 (62.9%) were females, with a mean age of 35.5 ± 11.7 years. Subgroup meta-analysis found significant variability in effect sizes across countries and types of specialty, of which Brazil showed the highest proportion and dermatology exhibited the smallest. Meta-regression analysis found no significant relationship between the year of publication and prevalence rates. (4) Conclusions: Our findings update the current literature on BDD prevalence in aesthetic and reconstructive plastic surgery. We emphasize the importance of proactive screening and multidisciplinary care approaches to address the complex challenges posed by patients with BDD. Further research is needed to explore evolving trends in BDD prevalence and factors influencing its expression across different cultural contexts.

16.
Pain ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981063

ABSTRACT

ABSTRACT: Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N = 233; mean age = 40.8 years, range 22-64 years; mean time since diagnosis = 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR = 1.6, 95% CI 1.1-2.3), respiratory (PR = 1.8, 95% CI 1.2-2.5), gastrointestinal (PR = 1.6, 95% CI 11.0-2.3), and neurological (PR = 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR = 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR = 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR = 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed.

17.
bioRxiv ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-39026717

ABSTRACT

Systems neuroscience has experienced an explosion of new tools for reading and writing neural activity, enabling exciting new experiments such as all-optical or closed-loop control that effect powerful causal interventions. At the same time, improved computational models are capable of reproducing behavior and neural activity with increasing fidelity. Unfortunately, these advances have drastically increased the complexity of integrating different lines of research, resulting in the missed opportunities and untapped potential of suboptimal experiments. Experiment simulation can help bridge this gap, allowing model and experiment to better inform each other by providing a low-cost testbed for experiment design, model validation, and methods engineering. Specifically, this can be achieved by incorporating the simulation of the experimental interface into our models, but no existing tool integrates optogenetics, two-photon calcium imaging, electrode recording, and flexible closed-loop processing with neural population simulations. To address this need, we have developed Cleo: the Closed-Loop, Electrophysiology, and Optophysiology experiment simulation testbed. Cleo is a Python package enabling injection of recording and stimulation devices as well as closed-loop control with realistic latency into a Brian spiking neural network model. It is the only publicly available tool currently supporting two-photon and multi-opsin/wavelength optogenetics. To facilitate adoption and extension by the community, Cleo is open-source, modular, tested, and documented, and can export results to various data formats. Here we describe the design and features of Cleo, validate output of individual components and integrated experiments, and demonstrate its utility for advancing optogenetic techniques in prospective experiments using previously published systems neuroscience models.

18.
J Antimicrob Chemother ; 79(8): 2017-2021, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38958234

ABSTRACT

OBJECTIVES: To investigate clinical outcomes of patients with Pseudomonas endocarditis and identify factors associated with treatment failure. METHODS: Adult patients meeting definitive Duke's criteria for Pseudomonas endocarditis at 11 hospitals were identified between May 2000 and February 2024. Failure was defined as death or microbiological failure by day 42. First-line therapy consisted of cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam alone or in combination. RESULTS: Forty-eight patients met inclusion criteria; 29% were persons who inject drugs and 13% were organ transplant recipients. Pseudomonas aeruginosa was the causative species in 98% of cases. Patients who experienced 42 day cure were more likely to be initially managed with first-line ß-lactam agents compared with those who experienced clinical failure (97% versus 62%, P = 0.004). Treatment with first-line ß-lactams was associated with shorter time to treatment initiation and a lower likelihood of infection due to MDR Pseudomonas spp. In the univariate model, patients who experienced 90 day mortality were more likely to have prosthetic valve endocarditis (57% versus 24%, P = 0.02), an intracardiac complication (36% versus 9%, P = 0.04) and a higher median (IQR) Pitt bacteraemia score [2.5 (2-3.8) versus 1 (0-2), P = 0.048]. Combination therapy did not improve clinical outcomes but did increase the rate of adverse effects resulting in drug discontinuation compared with monotherapy, (21% versus 0%, P = 0.08). CONCLUSIONS: This is the largest study of Pseudomonas endocarditis to date. We identified improved clinical outcomes when cefepime, piperacillin/tazobactam, ceftazidime or ceftolozane/tazobactam were used for initial treatment. We did not identify a clinical benefit for combination treatment.


Subject(s)
Anti-Bacterial Agents , Endocarditis, Bacterial , Pseudomonas Infections , Pseudomonas aeruginosa , Humans , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas Infections/mortality , Male , Female , Middle Aged , Anti-Bacterial Agents/therapeutic use , Endocarditis, Bacterial/drug therapy , Endocarditis, Bacterial/microbiology , Endocarditis, Bacterial/mortality , Adult , Aged , Pseudomonas aeruginosa/drug effects , Treatment Outcome , Tazobactam/therapeutic use , Retrospective Studies , Treatment Failure , Piperacillin, Tazobactam Drug Combination/therapeutic use , Cephalosporins
19.
Plast Reconstr Surg Glob Open ; 12(7): e5937, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38962153

ABSTRACT

Background: The highly competitive nature of the integrated plastic surgery residency match justifies the need for objective data that provide insights into some of the residents' selection criteria. Many studies have sought to provide information on these criteria, but to our knowledge, none has described the inflection point where the match probability does not further increase. Although our study provides this information to potential applicants, it will also help them assess and optimize their chances of a successful match. Methods: We pooled and analyzed the data available on matched and unmatched integrated plastic surgery applicants on the national residency match program database between 2016 and 2022. Results: Step 2 score of 250 or more (P < 0.0001), number of publications more than 15 (P = 0.0007), number of research experiences five or more (P = 0.018), number of contiguous ranks more than 10 (P < 0.0001), number of volunteer experiences five or more (P < 0.0001), being a US MD applicant (P < 0.0001), and Alpha Omega Alpha membership (P < 0.0001) were all associated with increased probability of matching into the integrated plastic surgery program. Match probability did not further increase after 15 publications, five research experiences, 15 contiguous ranks, and 10 volunteer experiences have been reached. Having a PhD (P = 0.149) or a non-PhD graduate degree (P = 0.07) was not associated with increased match probability. Conclusion: The law of diminishing returns sets in for applicants to the integrated plastic surgery match after 15 publications, 15 contiguous ranks, five research experiences, and 10 volunteer experiences have been reached.

20.
Ann Surg Oncol ; 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38955992

ABSTRACT

BACKGROUND: Immediate lymphatic reconstruction (ILR) has been proposed to decrease lymphedema rates. The primary aim of our study was to determine whether ILR decreased the incidence of lymphedema in patients undergoing axillary lymph node dissection (ALND). METHODS: We conducted a two-site pragmatic study of ALND with or without ILR, employing surgeon-level cohort assignment, based on breast surgeons' preferred standard practice. Lymphedema was assessed by limb volume measurements, patient self-reporting, provider documentation, and International Classification of Diseases, Tenth Revision (ICD-10) codes. RESULTS: Overall, 230 patients with breast cancer were enrolled; on an intention-to-treat basis, 99 underwent ALND and 131 underwent ALND with ILR. Of the 131 patients preoperatively planned for ILR, 115 (87.8%) underwent ILR; 72 (62.6%) were performed by one breast surgical oncologist and 43 (37.4%) by fellowship-trained microvascular plastic surgeons. ILR was associated with an increased risk of lymphedema when defined as ≥10% limb volume change on univariable analysis, but not on multivariable analysis, after propensity score adjustment. We did not find a statistically significant difference in limb volume measurements between the two cohorts when including subclinical lymphedema (≥5% inter-limb volume change), nor did we see a difference in grade between the two cohorts on an intent-to-treat or treatment received basis. For all patients, considering ascertainment strategies of patient self-reporting, provider documentation, and ICD-10 codes, as a single binary outcome measure, there was no significant difference in lymphedema rates between those undergoing ILR or not. CONCLUSION: We found no significant difference in lymphedema rates between patients undergoing ALND with or without ILR.

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