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Abstract Objective The purpose of this scoping review was to summarize the literature pertaining to burnout and chiropractic. Methods A literature review was performed in accordance with Preferred Reporting of Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR). A literature review was performed by combining the term “chiropractic” with terms relevant to professional burnout (e.g., “work-related stress,” “emotional exhaustion”). We included all publications addressing burnout within the chiropractic profession, including all study designs in only peer-reviewed literature. Results Our search yielded 126 citations and 10 met the inclusion criteria. The studies identified consisted of eight surveys and two narrative reviews published from 2011 to 2024. Six of the studies utilized the Maslach Burnout Inventory to assess burnout. Chiropractic students reported greater burnout than the general population. Factors reported to increase burnout risk include higher workload, insurance mandates, and physical demands of daily practice. Factors reported to be protective against burnout included longer duration in clinical practice and philosophy-based practices. Conclusions Research on burnout within the chiropractic profession is limited and may not be generalizable. However, the reported factors contributing to burnout are well-documented. Future research should be conducted to improve understanding of the prevalence and causes of burnout in chiropractic.

Objective. To estimate the national and regional population attributable fraction (PAF) and potential number of preventable anemia cases for three nutritional risk factors (iron, red blood cell folate [RBCF], and vitamin B12 deficiencies) among women of childbearing age in Belize. Methods. A national probability-based household and micronutrient survey capturing sociodemographic and health information was conducted among 937 nonpregnant Belizean women aged 15–49 years. Blood samples were collected to determine hemoglobin, ferritin, alpha-1-glycoprotein (AGP), RBCF, and vitamin B12 status. All analyses used sample weights and design variables to reflect a complex sample survey. Logistic regression was used to determine adjusted prevalence risk (aPR) ratios, which were then used to estimate national and regional PAF for anemia. Results. The overall prevalence of anemia (hemoglobin

Abstract Background Patients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years’ follow-up. Methods We searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits. Results Following propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35–0.85; P = 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6). Conclusions This study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture. Registration Open Science Framework ( https://osf.io/vgrwz ).

Abstract Background Deep learning models applied to healthcare applications including digital pathology have been increasing their scope and importance in recent years. Many of these models have been trained on The Cancer Genome Atlas (TCGA) atlas of digital images, or use it as a validation source. One crucial factor that seems to have been widely ignored is the internal bias that originates from the institutions that contributed WSIs to the TCGA dataset, and its effects on models trained on this dataset. Methods 8,579 paraffin-embedded, hematoxylin and eosin stained, digital slides were selected from the TCGA dataset. More than 140 medical institutions (acquisition sites) contributed to this dataset. Two deep neural networks (DenseNet121 and KimiaNet were used to extract deep features at 20× magnification. DenseNet was pre-trained on non-medical objects. KimiaNet has the same structure but trained for cancer type classification on TCGA images. The extracted deep features were later used to detect each slide’s acquisition site, and also for slide representation in image search. Results DenseNet’s deep features could distinguish acquisition sites with 70% accuracy whereas KimiaNet’s deep features could reveal acquisition sites with more than 86% accuracy. These findings suggest that there are acquisition site specific patterns that could be picked up by deep neural networks. It has also been shown that these medically irrelevant patterns can interfere with other applications of deep learning in digital pathology, namely image search. Summary This study shows that there are acquisition site specific patterns that can be used to identify tissue acquisition sites without any explicit training. Furthermore, it was observed that a model trained for cancer subtype classification has exploited such medically irrelevant patterns to classify cancer types. Digital scanner configuration and noise, tissue stain variation and artifacts, and source site patient demographics are among factors that likely account for the observed bias. Therefore, researchers should be cautious of such bias when using histopathology datasets for developing and training deep networks.

Abstract Background This review aimed to identify variables influencing clinicians’ application of spinal manipulative therapy (SMT) for persistent spine pain after lumbar surgery (PSPS-2). We hypothesized markers of reduced clinical/surgical complexity would be associated with greater odds of applying SMT to the lumbar region, use of manual-thrust lumbar SMT, and SMT within 1-year post-surgery as primary outcomes; and chiropractors would have increased odds of using lumbar manual-thrust-SMT compared to other practitioners. Methods Per our published protocol, observational studies describing adults receiving SMT for PSPS-2 were included. PubMed, Web of Science, Scopus, OVID, PEDro, and Index to Chiropractic Literature were searched from inception to January 6, 2022. Individual patient data (IPD) were requested from contact authors when needed for selection criteria. Data extraction and a customized risk-of-bias rubric were completed in duplicate. Odds ratios (ORs) for primary outcomes were calculated using binary logistic regressions, with covariates including age, sex, symptom distribution, provider, motion segments, spinal implant, and surgery-to-SMT interval. Results 71 articles were included describing 103 patients (mean age 52 ± 15, 55% male). The most common surgeries were laminectomy (40%), fusion (34%), and discectomy (29%). Lumbar SMT was used in 85% of patients; and of these patients was non-manual-thrust in 59%, manual-thrust in 33%, and unclear in 8%. Clinicians were most often chiropractors (68%). SMT was used > 1-year post-surgery in 66% of cases. While no primary outcomes reached significance, non-reduced motion segments approached significance for predicting use of lumbar-manual-thrust SMT (OR 9.07 [0.97–84.64], P = 0.053). Chiropractors were significantly more likely to use lumbar-manual-thrust SMT (OR 32.26 [3.17–327.98], P = 0.003). A sensitivity analysis omitting high risk-of-bias cases (missing ≥ 25% IPD) revealed similar results. Conclusions Clinicians using SMT for PSPS-2 most often apply non-manual-thrust SMT to the lumbar spine, while chiropractors are more likely to use lumbar-manual-thrust SMT relative to other providers. As non-manual-thrust SMT may be gentler, the proclivity towards this technique suggests providers are cautious when applying SMT after lumbar surgery. Unmeasured variables such as patient or clinician preferences, or limited sample size may have influenced our findings. Large observational studies and/or international surveys are needed for an improved understanding of SMT use for PSPS-2. Systematic review registration PROSPERO (CRD42021250039).

Introduction: Surgical management of degenerative lumbar spine disorders is effective at improving patient pain, disability, and quality of life; however, obtaining a durable posterolateral fusion after decompression remains a challenge. Interbody fusion technologies are viable means of improving fusion rates in the lumbar spine, specifically various graft materials including autograft, structural allograft, titanium, and polyether ether ketone. This study assesses the effectiveness of Tritanium posterolateral cage in the treatment of degenerative disk disease. Methods: Nearest-neighbor 1:1 matched control transforaminal lumbar interbody fusion with PEEK vs. Tritanium posterior lumbar (PL) cage interbody fusion patients were identified using propensity scoring from patients that underwent elective surgery for degenerative disk diseases. Line graphs were generated to compare the trajectories of improvement in patient-reported outcomes (PROs) from baseline to 3 and 12 months postoperatively. The nominal data were compared via the χ2 test, while the continuous data were compared via Student's t-test. Results: The two groups had no difference regarding either the 3- or 12-month Euro-Qol-5D (EQ-5D), numeric rating scale (NRS) leg pain, and NRS back pain; however, the Tritanium interbody cage group had better Oswestry Disability Index (ODI) scores compared to the control group of the PEEK interbody cage at both 3 and 12 months (p=0.013 and 0.048). Conclusions: Our results indicate the Tritanium cage is an effective alternative to the previously used PEEK cage in terms of PROs, surgical safety, and radiological parameters of surgical success. The Tritanium cohort showed better ODI scores, higher fusion rates, lower subsidence, and lower indirect costs associated with surgical management, when compared to the propensity-matched PEEK cohort.

Abstract Objective To identify and descriptively compare medication recommendations among low back pain (LBP) clinical practice guidelines (CPG). Methods We searched PubMed, Cochrane Database of Systematic Review, Index to Chiropractic Literature, AMED, CINAHL, and PEDro to identify CPGs that described the management of mechanical LBP in the prior five years. Two investigators independently screened titles and abstracts and potentially relevant full text were considered for eligibility. Four investigators independently applied the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument for critical appraisal. Data were extracted for pharmaceutical intervention, the strength of recommendation, and appropriateness for the duration of LBP. Results 316 citations were identified, 50 full-text articles were assessed, and nine guidelines with global representation met the eligibility criteria. These CPGs addressed pharmacological treatments with or without non-pharmacological treatments. All CPGS focused on the management of acute, chronic, or unspecified duration of LBP. The mean overall AGREE II score was 89.3% (SD 3.5%). The lowest domain mean score was for applicability, 80.4% (SD 5.2%), and the highest was Scope and Purpose, 94.0% (SD 2.4%). There were ten classifications of medications described in the included CPGs: acetaminophen, antibiotics, anticonvulsants, antidepressants, benzodiazepines, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral corticosteroids, skeletal muscle relaxants (SMRs), and atypical opioids. Conclusions Nine CPGs, included ten medication classes for the management of LBP. NSAIDs were the most frequently recommended medication for the treatment of both acute and chronic LBP as a first line pharmacological therapy. Acetaminophen and SMRs were inconsistently recommended for acute LBP. Meanwhile, with less consensus among CPGs, acetaminophen and antidepressants were proposed as second-choice therapies for chronic LBP. There was significant heterogeneity of recommendations within many medication classes, although oral corticosteroids, benzodiazepines, anticonvulsants, and antibiotics were not recommended by any CPGs for acute or chronic LBP.

Moosavi Tayebi et al. develop a deep learning-based computational pathology tool for automated bone marrow cytology from whole slide images. Their approach generates a histogram of cell types present within the bone marrow aspirate to aid in diagnostic haematopathology.

Abstract Objective Cervical spine surgeries for degenerative conditions are rapidly increasing. Cervical post-surgery syndrome consisting of chronic pain, adjacent segment disease, recurrent disc herniation, facet joint pain, and/or epidural scarring is common. Repeat surgery is regularly recommended, though patients are often unable to undergo or decline further surgery. Manual therapy is included in clinical practice guidelines for neck pain and related disorders, however clinical guidance for utilization of manual therapy in adults with prior cervical spine surgery is lacking. This study aimed to synthesize available literature and characterize outcomes and adverse events for manual therapy interventions in adults with prior cervical spine surgery due to degenerative conditions. Methods Preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews was followed. PubMed, Cumulative Index of Nursing and Allied Health Literature, physiotherapy evidence database, and Index to Chiropractic Literature were searched from inception through October 2021. English-language literature comprised of randomized clinical trials (RCT), case–control, cohort, and case report designs were included. Adults undergoing manual therapy, with or without combination of other interventions, with prior cervical spine surgery due to degenerative conditions were included. Results Twelve articles were identified, including 10 case reports, 1 low-quality RCT, and 1 acceptable-quality RCT. Eight case reports described 9 patients with history of fusion surgery. Two case reports described 2 patients with history of discectomy. One case report described one patient with separate operations of a discectomy at one level and a fusion at another level. One case report described 2 patients with history of cervical disc replacement surgery. The two RCTs included 63 and 86 participants, respectively. Use of manual joint mobilization/manipulation, table/instrument assisted mobilization/manipulation, and multimodal interventions were described in eligible studies. Favorable clinical outcomes were reported in 10 studies. Six case reports/series involving 8 patients described use of unclassified forms of manual therapy. Eight studies described the use of multimodal interventions along with manual therapy. One study described high patient satisfaction. Two studies, accounting for 3 patients, reported serious adverse events. Conclusions There is a lack of literature informing evidence related to clinical outcomes, patient satisfaction, and adverse events associated with manual therapy for patients with prior cervical spine surgery due to degenerative conditions. High-quality studies of higher-level hierarchical study design are needed to understand the clinical utility and safety profile of manual therapy for this population.

Abstract. Objectives:. To compare operative rates, total hospital charges, and length of stay between different socioeconomic cohorts in treating distal radius fractures (DRFs). Design:. A retrospective cohort study. Setting:. Large public level 1 trauma center. Patients:. A retrospective search of all trauma activations over a 7-year period (2013–2020) yielded 816 adult patients diagnosed with DRF. Patients were separated into cohorts of socioeconomic status based on 2010 US Census data and insurance status. Intervention:. DRFs were treated either nonoperatively using closed reduction and splinting or operatively using open reduction and internal fixation, closed reduction percutaneous pinning, or external fixator application. Main Outcome Measurements:. Operative rates of DRF, total hospital charges, and length of stay. Results:. Patients who were uninsured or in the low-income socioeconomic cohort had no significant difference in operative rates, total hospital costs, or length of stay when compared with their respective insured or standard income groups. Younger patients and those with OTA/AO type C, bilateral, or open DRFs were more likely to undergo operative intervention. Conclusions:. This study demonstrates that low socioeconomic status based on annual household income and insurance status was not associated with differences in operative rates on DRFs, length of stay, or total hospital charges. These results suggest that outcome disparities between groups may be caused by postoperative differences rather than treatment decision-making. Although this study investigates access to surgical care at a publicly funded level 1 trauma center, disparities may still exist in other models of care. Level of Evidence:. Prognostic Level III.

Objectives Chiropractic spinal manipulative therapy (CSMT) and lumbar discectomy are both used for lumbar disc herniation (LDH) and lumbosacral radiculopathy (LSR); however, limited research has examined the relationship between these therapies. We hypothesised that adults receiving CSMT for newly diagnosed LDH or LSR would have reduced odds of lumbar discectomy over 1-year and 2-year follow-up compared with those receiving other care.Design Retrospective cohort study.Setting 101 million patient US health records network (TriNetX), queried on 24 October 2022, yielding data from 2012 query.Participants Adults age 18–49 with newly diagnosed LDH/LSR (first date of diagnosis) were included. Exclusions were prior lumbar surgery, absolute indications for surgery, trauma, spondylolisthesis and scoliosis. Propensity score matching controlled for variables associated with the likelihood of discectomy (eg, demographics, medications).Interventions Patients were divided into cohorts according to receipt of CSMT.Primary and secondary outcome measures ORs for lumbar discectomy; calculated by dividing odds in the CSMT cohort by odds in the cohort receiving other care.Results After matching, there were 5785 patients per cohort (mean age 36.9±8.2). The ORs (95% CI) for discectomy were significantly reduced in the CSMT cohort compared with the cohort receiving other care over 1-year (0.69 (0.52 to 0.90), p=0.006) and 2-year follow-up (0.77 (0.60 to 0.99), p=0.040). E-value sensitivity analysis estimated the strength in terms of risk ratio an unmeasured confounding variable would need to account for study results, yielding point estimates for each follow-up (1 year: 2.26; 2 years: 1.92), which no variables in the literature reached.Conclusions Our findings suggest receiving CSMT compared with other care for newly diagnosed LDH/LSR is associated with significantly reduced odds of discectomy over 2-year follow-up. Given socioeconomic variables were unavailable and an observational design precludes inferring causality, the efficacy of CSMT for LDH/LSR should be examined via randomised controlled trial to eliminate residual confounding.

Abstract Background The purpose of this study was to investigate the longitudinal postoperative relationship between physical activity, psychosocial factors, and physical function in patients undergoing lumbar spine surgery. Methods We enrolled 248 participants undergoing surgery for a degenerative lumbar spine condition. Physical activity was measured using a triaxial accelerometer (Actigraph GT3X) at 6-weeks (6wk), 6-months (6M), 12-months (12M) and 24-months (24M) following spine surgery. Physical function (computerized adaptive test domain version of Patient-Reported Outcomes Measurement Information System) and psychosocial factors (pain self-efficacy, depression and fear of movement) were assessed at preoperative visit and 6wk, 6M, 12M and 24M after surgery. Structural equation modeling (SEM) techniques were utilized to analyze data, and results are represented as standardized regression weights (SRW). Overall SRW were computed across five imputed datasets to account for missing data. The mediation effect of each psychosocial factor on the effect of physical activity on physical function were computed [(SRW for effect of activity on psychosocial factor X SRW for effect of psychosocial factor on function) ÷ SRW for effect of activity on function]. Each SEM model was tested for model fit by assessing established fit indexes. Results The overall effect of steps per day on physical function (SRW ranged from 0.08 to 0.19, p

Summary: Biologically active small molecules can impart modulatory effects, in some cases providing extended long-term memory. In a screen of biologically active small molecules for regulators of tumor necrosis factor (TNF) induction, we identify several compounds with the ability to induce training effects on human macrophages. Rutaecarpine shows acute and long-term modulation, enhancing lipopolysaccharide (LPS)-induced pro-inflammatory cytokine secretion and relieving LPS tolerance in human macrophages. Rutaecarpine inhibits β-glucan-induced H3K4Me3 marks at the promoters of several pro-inflammatory cytokines, highlighting the potential of this molecule to modulate chromosomal topology. Syk kinase inhibitor (SYKi IV), another screen hit, promotes an enhanced response to LPS similar to that previously reported for β-glucan-induced training. Macrophages trained with SYKi IV show a high degree of resistance to influenza A, multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and OC43 coronavirus infection, highlighting a potential application of this molecule and other SYKis as prophylactic treatments for viral susceptibility.

Abstract Background Suicide is a major public health concern that has wide-reaching implications on individuals, families, and society. Efforts to respond to a public health concern as a portal-of-entry provider can reduce morbidity and mortality of patients. The objective of this commentary is a call to action to initiate dialogue regarding suicide prevention and the role the chiropractic profession may play. Discussion This public health burden requires doctors of chiropractic to realize current strengths and recognize contemporaneous deficiencies in clinical, research, and policy environments. With this better understanding, only then can the chiropractic profession strive to enhance knowledge and promote clinical acumen to target and mitigate suicide risk to better serve the public. Conclusion We implore the profession to transition from bystander to actively engaged in the culture of suicide prevention beholden to all aspects of the biopsychosocial healthcare model. The chiropractic profession’s participation in suicide prevention improves the health and wellness of one’s community while also impacting the broader public health arena.

Background: The risks of femoral arterial line placement in young children have been incompletely defined. We hypothesized that a low complication rate would be associated with ultrasound use. Subjects and Methods: Infants aged 0–12 months undergoing placement of a femoral arterial line at our institution over a 3.5-year period were identified through billing data, and their records were reviewed. Events concerning each line were recorded individually. Patients were excluded if there was incomplete documentation or if the line was in place for under 24 h. Demographics, information about line placement, and complications were recorded. Results: Three hundred and sixty-four femoral arterial lines were included. Eighty percent of lines were placed in the operating room, with the rest placed in the cardiac intensive care unit (ICU) (11%), the cardiac catheterization lab (6%), or the pediatric ICU (3%). Femoral artery occlusion occurred with 16% of lines placed, and limb ischemia in 6%. One patient had tissue loss. Occlusion was associated with lower gestational age at birth (44 [40–57] vs. 50 [41–60], P = 0.04), lower weight (3.7 [3.1–5.7] vs. 4.3 kg [3.3–6.2], P = 0.05), left-sided lines (52% vs. 66%, P = 0.05), placement in interventional catheterization lab (odds ratio [OR]: 3.28, confidence interval [CI]: 1.24–8.67, P = 0.02), >2 attempts (27% vs. 13%, P < 0.01), and catheter diameter (OR: 2.86, CI: 1.18–6.92, P = 0.02). Conclusion: Femoral arterial catheter placement in infants younger than 12 months resulted in a 16% rate of arterial occlusion at our institution, which was associated with low gestational age, larger catheter size, and left-sided lines but not ultrasound use, line duration, catheter length, use of anticoagulation, physician specialty, or physician training level.

Abstract Background The purpose of this prospective case series study was to compare changes in early postoperative physical activity and physical function between 6 weeks and 3 and 6 months after lumbar spine surgery. Methods Fifty-three patients (mean [95% confidence interval; CI] age = 59.2 [56.2, 62.3] years, 64% female) who underwent spine surgery for a degenerative lumbar condition were assessed at 6 weeks and 3- and 6-months after surgery. The outcomes were objectively-measured physical activity (accelerometry) and patient-reported and objective physical function. Physical activity was assessed using mean steps/day and time spent in moderate to vigorous physical activity (MVPA) over a week. Physical function measures included Oswestry Disability Index (ODI), 12-item Short Form Health Survey (SF-12), Timed Up and Go (TUG), and 10-Meter Walk (10 MW). We compared changes over time in physical activity and function using generalized estimating equations with robust estimator and first-order autoregressive covariance structure. Proportion of patients who engaged in meaningful physical activity (e.g., walked at least 4400 and 6000 steps/day or engaged in at least 150 min/week in MVPA) and achieved clinically meaningful changes in physical function were compared at 3 and 6 months. Results After surgery, 72% of patients initiated physical therapy (mean [95%CI] sessions =8.5 [6.6, 10.4]) between 6 weeks and 3 months. Compared to 6 weeks post-surgery, no change in steps/day or time in MVPA/week was observed at 3 or 6 months. From 21 to 23% and 9 to 11% of participants walked at least 4400 and 6000 steps/day at 3 and 6 months, respectively, while none of the participants spent at least 150 min/week in MVPA at these same time points. Significant improvements were observed on ODI, SF-12, TUG and 10 MW (p

Abstract Background Little is known about the preferred treatment strategies of chiropractors in managing low back pain patients with prior lumbar fusions. There are several case reports which describe chiropractic care following surgical intervention, but there are no cohort or experimental studies published. Therefore, we sought to examine self-reported management approaches and practice patterns related to the management of patients with prior surgical lumbar fusion, among United States Veterans Affairs (VA) chiropractors. Methods An electronic survey was administered nationwide to all chiropractors providing clinical care within VA. Questions were informed by a prior survey and piloted on a sample of chiropractors external to VA. Statistical analysis included respondent background information, and quantitative analysis of chiropractic referral patterns and practices. This survey collect information on 1) provider demographics, 2) VA referral patterns, and 3) attitudes, beliefs, practices and interventions utilized by VA chiropractors to manage patients with a history of surgical lumbar fusion. Results The survey response rate was 46.3% (62/134). The respondents were broadly representative of VA chiropractic providers in age, gender, and years in practice. The majority of respondents (90.3%) reported seeing at least 1 post-fusion patient in the past month. The most common therapeutic approaches utilized by VA chiropractors were healthy lifestyle advice (94.9%), pain education (89.8%), exercise prescription (88.1%), stretching (66.1%) and soft tissue manual therapies (62.7%). A relatively smaller proportion described always or frequently incorporating lumbar (16.9%), thoracic (57.6%) or pelvic (39.0%) spinal manipulation. Conclusion This survey provides preliminary data on VA chiropractic services in the management of patients with prior lumbar fusion. These patients are often seen by VA chiropractors, and our findings support the need for further study to advance understanding of interventions utilized by chiropractors in this patient population.

Drought stress causes the greatest soybean [Glycine max (L.) Merr.] yield losses among the abiotic stresses in rain-fed U.S. growing areas. Because less than 10% of U.S. soybean hectares are irrigated, combating this stress requires soybean plants which possess physiological mechanisms to tolerate drought for a period of time. Phenotyping for these mechanisms is challenging, and the genetic architecture for these traits is poorly understood. A morphological trait, slow or delayed canopy wilting, has been observed in a few exotic plant introductions (PIs), and may lead to yield improvement in drought stressed fields. In this study, we visually scored wilting during stress for a panel of 162 genetically diverse maturity group VI-VIII soybean lines genotyped with the SoySNP50K iSelect BeadChip. Field evaluation of canopy wilting was conducted under rain-fed conditions at two locations (Athens, GA and Salina, KS) in 2015 and 2016. Substantial variation in canopy wilting was observed among the genotypes. Using a genome-wide association mapping approach, 45 unique SNPs that tagged 44 loci were associated with canopy wilting in at least one environment with one region identified in a single environment and data from across all environments. Several new soybean accessions were identified with canopy wilting superior to those of check genotypes. The germplasm and genomic regions identified can be used to better understand the slow canopy wilting trait and be incorporated into elite germplasm to improve drought tolerance in soybean.

Abstract The emergence of digital pathology has opened new horizons for histopathology. Artificial intelligence (AI) algorithms are able to operate on digitized slides to assist pathologists with different tasks. Whereas AI-involving classification and segmentation methods have obvious benefits for image analysis, image search represents a fundamental shift in computational pathology. Matching the pathology of new patients with already diagnosed and curated cases offers pathologists a new approach to improve diagnostic accuracy through visual inspection of similar cases and computational majority vote for consensus building. In this study, we report the results from searching the largest public repository (The Cancer Genome Atlas, TCGA) of whole-slide images from almost 11,000 patients. We successfully indexed and searched almost 30,000 high-resolution digitized slides constituting 16 terabytes of data comprised of 20 million 1000 × 1000 pixels image patches. The TCGA image database covers 25 anatomic sites and contains 32 cancer subtypes. High-performance storage and GPU power were employed for experimentation. The results were assessed with conservative “majority voting” to build consensus for subtype diagnosis through vertical search and demonstrated high accuracy values for both frozen section slides (e.g., bladder urothelial carcinoma 93%, kidney renal clear cell carcinoma 97%, and ovarian serous cystadenocarcinoma 99%) and permanent histopathology slides (e.g., prostate adenocarcinoma 98%, skin cutaneous melanoma 99%, and thymoma 100%). The key finding of this validation study was that computational consensus appears to be possible for rendering diagnoses if a sufficiently large number of searchable cases are available for each cancer subtype.

Pathogenic variants in BRAT1 are associated with a spectrum of clinical syndromes ranging from Lethal Neonatal Rigidity and Multifocal Seizure syndrome (RMFSL) to Neurodevelopmental Disorder with Cerebellar Atrophy and with or without Seizures (NEDCAS). RMFSL is characterized by early-onset multifocal seizures with microcephaly. Death occurs during infancy although a less severe course with later onset seizures and longer survival into childhood has been described. Here, we summarize published cases of BRAT1 disorders and present the case of a 20-year-old man with two heterozygous BRAT1 variants and a relatively later age of seizure onset with survival into adulthood. This case expands the spectrum of disease associated with BRAT1 variants and highlights the utility of genetic testing to identify the cause of developmental and epileptic encephalopathies where clinical heterogeneity within a spectrum of disease exists.

Tuberculosis (TB) control programs use whole-genome sequencing (WGS) of Mycobacterium tuberculosis (Mtb) for detecting and investigating TB case clusters. Existence of few genomic differences between Mtb isolates might indicate TB cases are the result of recent transmission. However, the variable and sometimes long duration of latent infection, combined with uncertainty in the Mtb mutation rate during latency, can complicate interpretation of WGS results. To estimate the association between infection duration and single nucleotide polymorphism (SNP) accumulation in the Mtb genome, we first analyzed pairwise SNP differences among TB cases from Los Angeles County, California, with strong epidemiologic links. We found that SNP distance alone was insufficient for concluding that cases are linked through recent transmission. Second, we describe a well-characterized cluster of TB cases in California to illustrate the role of genomic data in conclusions regarding recent transmission. Longer presumed latent periods were inconsistently associated with larger SNP differences. Our analyses suggest that WGS alone cannot be used to definitively determine that a case is attributable to recent transmission. Methods for integrating clinical, epidemiologic, and genomic data can guide conclusions regarding the likelihood of recent transmission, providing local public health practitioners with better tools for monitoring and investigating TB transmission.

Abstract Background Drought stress is a major limiting factor of soybean [Glycine max (L.) Merr.] production around the world. Soybean plants can ameliorate this stress with improved water-saving, sustained N2 fixation during water deficits, and/or limited leaf hydraulic conductance. In this study, carbon isotope composition (δ13C), which can relate to variation in water-saving capability, was measured. Additionally, nitrogen isotope composition (δ15N) and nitrogen concentration that relate to nitrogen fixation were evaluated. Decrease in transpiration rate (DTR) of de-rooted soybean shoots in a silver nitrate (AgNO3) solution compared to deionized water under high vapor pressure deficit (VPD) conditions was used as a surrogate measurement for limited leaf hydraulic conductance. A panel of over 200 genetically diverse soybean accessions genotyped with the SoySNP50K iSelect BeadChips was evaluated for the carbon and nitrogen related traits in two field environments (Athens, GA in 2015 and 2016) and for transpiration response to AgNO3 in a growth chamber. A multiple loci linear mixed model was implemented in FarmCPU to perform genome-wide association analyses for these traits. Results Thirty two, 23, 26, and nine loci for δ13C, δ15N, nitrogen concentration, and transpiration response to AgNO3, respectively, were significantly associated with these traits. Candidate genes that relate to drought stress tolerance enhancement or response were identified near certain loci that could be targets for improving and understanding these traits. Soybean accessions with favorable breeding values were also identified. Low correlations were observed between many of the traits and the genetic loci associated with each trait were largely unique, indicating that these drought tolerance related traits are governed by different genetic loci. Conclusions The genomic regions and germplasm identified in this study can be used by breeders to understand the genetic architecture for these traits and to improve soybean drought tolerance. Phenotyping resources needed, trait heritability, and relationship to the target environment should be considered before deciding which of these traits to ultimately employ in a specific breeding program. Potential marker-assisted selection efforts could focus on loci which explain the greatest amount of phenotypic variation for each trait, but may be challenging due to the quantitative nature of these traits.

Abstract Soybean [Glycinemax (L.) Merr.] maturity determines the growing region of a given soybean variety and is a primary factor in yield and other agronomic traits. The objectives of this research were to identify the quantitative trait loci (QTL) associated with maturity groups (MGs) and determine the genetic control of soybean maturity in each MG. Using data from 16,879 soybean accessions, genome‐wide association (GWA) analyses were conducted for each paired MG and across MGs 000 through IX. Genome‐wide association analyses were also performed using 184 genotypes (MGs V–IX) with days to flowering (DTF) and maturity (DTM) collected in the field. A total of 58 QTL were identified to be significantly associated with MGs in individual GWAs, which included 12 reported maturity loci and two stem termination genes. Genome‐wide associations across MGs 000–IX detected a total of 103 QTL and confirmed 54 QTL identified in the individual GWAs. Of significant loci identified, qMG‐5.2 had effects on the highest number (9) of MGs, followed by E2, E3, Dt2, qMG‐15.5, E1, qMG‐13.1, qMG‐7.1, and qMG‐16.1, which affected five to seven MGs. A high number of genetic loci (8–25) that affected MGs 0–V were observed. Stem termination genes Dt1 and Dt2 mainly had significant allele variation in MGs II–V. Genome‐wide associations for DTF, DTM, and reproductive period (RP) in the diversity panel confirmed 15 QTL, of which seven were observed in MGs V–IX. The results generated can help soybean breeders manipulate the maturity loci for genetic improvement of soybean yield.

Understanding tuberculosis (TB) transmission chains can help public health staff target their resources to prevent further transmission, but currently there are few tools to automate this process. We have developed the Logically Inferred Tuberculosis Transmission (LITT) algorithm to systematize the integration and analysis of whole-genome sequencing, clinical, and epidemiological data. Based on the work typically performed by hand during a cluster investigation, LITT identifies and ranks potential source cases for each case in a TB cluster. We evaluated LITT using a diverse dataset of 534 cases in 56 clusters (size range: 2–69 cases), which were investigated locally in three different U.S. jurisdictions. Investigators and LITT agreed on the most likely source case for 145 (80%) of 181 cases. By reviewing discrepancies, we found that many of the remaining differences resulted from errors in the dataset used for the LITT algorithm. In addition, we developed a graphical user interface, user's manual, and training resources to improve LITT accessibility for frontline staff. While LITT cannot replace thorough field investigation, the algorithm can help investigators systematically analyze and interpret complex data over the course of a TB cluster investigation.Code available at:https://github.com/CDCgov/TB_molecular_epidemiology/tree/1.0; https://zenodo.org/badge/latestdoi/166261171.

Forward genetics remains a powerful method for revealing the genes underpinning organismal form and function, and for revealing how these genes are tied together in gene networks. In maize, forward genetics has been tremendously successful, but the size and complexity of the maize genome made identifying mutant genes an often arduous process with traditional methods. The next generation sequencing revolution has allowed for the gene cloning process to be significantly accelerated in many organisms, even when genomes are large and complex. Here, we describe a bulked-segregant analysis sequencing (BSA-Seq) protocol for cloning mutant genes in maize. Our simple strategy can be used to quickly identify a mapping interval and candidate single nucleotide polymorphisms (SNPs) from whole genome sequencing of pooled F2 individuals. We employed this strategy to identify narrow odd dwarf as an enhancer of teosinte branched1, and to identify a new allele of defective kernel1. Our method provides a quick, simple way to clone genes in maize.

The mammalian immune system is constantly challenged by signals from both pathogenic and non-pathogenic microbes. Many of these non-pathogenic microbes have pathogenic potential if the immune system is compromised. The importance of type I interferons (IFNs) in orchestrating innate immune responses to pathogenic microbes has become clear in recent years. However, the control of opportunistic pathogens-and especially intracellular bacteria-by type I IFNs remains less appreciated. In this study, we use the opportunistic, Gram-negative bacterial pathogen Burkholderia cenocepacia (Bc) to show that type I IFNs are capable of limiting bacterial replication in macrophages, preventing illness in immunocompetent mice. Sustained type I IFN signaling through cytosolic receptors allows for increased expression of autophagy and linear ubiquitination mediators, which slows bacterial replication. Transcriptomic analyses and in vivo studies also show that LPS stimulation does not replicate the conditions of intracellular Gram-negative bacterial infection as it pertains to type I IFN stimulation or signaling. This study highlights the importance of type I IFNs in protection against opportunistic pathogens through innate immunity, without the need for damaging inflammatory responses.

Sight reading skills are widely considered to be crucial for all musicians. However, given that sight reading involves playing sheet music without having seen it before, once an exercise has been completed by a student it can no longer be used as a sight reading exercise for them. In this paper we present a novel evolutionary algorithm for generating musical sight reading exercises in the Western art music tradition. Using models based on expert examples, the algorithm generates material suitable for practice which is both technically appropriate and aesthetically pleasing with respect to an instrument and difficulty level. This overcomes the resource constraint in using traditional practice exercises, which are exhausted quickly by students and teachers due to their limited quantity.

Objective: Patient satisfaction is emerging as a new health-care metric. We hypothesized that an emergency department (ED) informational pamphlet would significantly improve patient understanding of ED operations and ultimately improve patient satisfaction. Methods: We performed a prospective study of patients presenting to a single tertiary care center ED from April to July 2017. All patients were given a pamphlet on alternating weeks with regular care on opposite weeks and were surveyed upon ED discharge. The primary outcome was patient satisfaction with ED care. Secondary outcomes included patient understanding of various wait times (test results, consultants), discharge process, who was on the care team and what to expect during the ED visit. Results: Four hundred ninety-four patients were included in this study and 266 (54%) were in the control group. Of 228 (46%) patients who were given the pamphlet, 116 (51%) were unaware they received it. Of the remaining 112 (49%) patients who remembered receiving the pamphlet, 43 (38%) stated they read it. Among those reading the pamphlet, only two statements were significant: knowing what to expect during the ED visit (88% vs 71%; P = 0.012) and waiting time for test results (95% vs 75%; P = 0.003) when compared to those who did not receive or read the pamphlet. Conclusion: An ED informational pamphlet, when utilized by patients, does improve patient understanding of some aspects of the ED visit but does not appear to be the best tool to convey all information. Ultimately, sustained improvement in patient satisfaction is a complex and dynamic issue necessitating a multifactorial approach and other methods should be explored.

Child mortality from rotavirus gastroenteritis remains high in Nigeria, representing 14% of all rotavirus deaths worldwide. Here, we examine the potential impact and cost-effectiveness of national rotavirus vaccine introduction in geographic and economic subpopulations of Nigeria. We projected the health and economic outcomes of rotavirus vaccination in children over the first five years of life using a spreadsheet-based model. We modeled child populations using national survey data on rotavirus mortality risk factors and vaccination coverage to predict burden and impact across regional and wealth quintile subpopulations within Nigeria. Our base case considered introduction of a general rotavirus vaccine, modeled to encompass characteristics of existing vaccines, versus no vaccine. Base case costs were estimated from the government perspective, assuming Gavi subsidies, over the first five years. We also present estimates from the cost of vaccination from the perspective of Gavi. We explored uncertainty in model parameters through probabilistic uncertainty, one-way sensitivity, and scenario analyses. According to our estimates, rotavirus enteritis was responsible for 47,898 [95% Uncertainty Limits: 35,361; 63,703] child deaths per year, with approximately 80% of the national burden concentrated in the three northern regions of Nigeria. Rotavirus vaccination was estimated to prevent 6,454 [3,960; 9,721] deaths, 13% [9%; 18%] of the national annual RV burden. National ICERs for rotavirus vaccination from the Nigerian government and Gavi perspectives were US$47 [$18; $105] and $62 [$29; $130] per DALY averted, respectively. General rotavirus vaccination was projected to reduce rotavirus mortality by only 6% [4%; 9%] in the North West region compared to 35% [24%; 47%] in the South East region. Base case ICERs ranged from US$25 [10; 56] per DALY averted in North West to US$64 [18; 157] per DALY averted in South South. Gavi perspective ICERs ranged from US$33 [$15; $68] in North West to US$88 [35; 191] per DALY averted in South South. According to one-way sensitivity analyses, ICERs were most sensitive to vaccine efficacy, followed by estimated administrative costs and rotavirus mortality. Disparities in mortality reduction were largely driven by inequality in vaccination coverage across regions and between socioeconomic subpopulations. Due to high, persistent, and inequitable burden of rotavirus in Nigeria, routine vaccination with any of these rotavirus vaccines would be an high impact and cost-effective strategy in reducing child mortality.

Abstract Background Spinal epidural lipomatosis is an uncommon source of neurogenic claudication. We present two cases of spinal epidural lipomatosis as it relates to diagnosis, management, and a possible association with common medical intervention. Case presentation Case 1: 63-year old male patient presented with neurogenic claudication symptoms, but without evidence of bony central canal stenosis on lumbar computed tomography. He entered a trial of spinal manipulation with transient beneficial gains after seven appointments, but no durable change in neurogenic claudication. An MRI was recommended at this point which revealed grade III spinal epidural lipomatosis at the L5/S1 level. Case 2: 51-year old male patient presented to a pain management physician with radicular symptoms for a series of lumbar epidural steroid injections. He completed a series of three lumbar epidural steroid injections with only short-term benefit. A repeat MRI demonstrated the presence of grade I (borderline grade II) spinal epidural lipomatosis. Conclusions The first case illustrates a limitation of ruling out central canal stenosis with computed tomography for patients unable to undergo an MRI. The second case demonstrates a possible association between steroid injections and spinal epidural lipomatosis. An association of this kind has not been established; further research is needed to determine the significance.

Darwin described evolution as “descent with modification.” Descent, however, is not an explicit focus of most evolution instruction and often leaves deeply held misconceptions to dominate student understanding of common ancestry and species relatedness. Evolutionary trees are ways of visually depicting descent by illustrating the relationships between species and groups of species. The ability to properly interpret and use evolutionary trees has become known as “tree thinking.” We used a 20-question assessment to measure misconceptions in tree thinking and compare the proportion of students who hold these misconceptions in an introductory biology course with students in two higher-level courses including a senior level biology course. We found that misconceptions related to reading the graphic (reading the tips and node counting) were variably influenced across time with reading the tips decreasing and node counting increasing in prevalence. On the other hand, misconceptions related to the fundamental underpinnings of evolutionary theory (ladder thinking and similarity equals relatedness) proved resistant to change during a typical undergraduate study of biology. A possible new misconception relating to the length of the branches in an evolutionary tree is described. Understanding the prevalence and persistence of misconceptions informs educators as to which misconceptions should be targeted in their courses.

Objective: We assessed whether provider sitting influenced patient satisfaction in an academic emergency department (ED) and if education and/or environmental manipulation could nudge providers to sit. Methods: This was a prospective, controlled pre–post trial of provider sitting and its influence on patient satisfaction within 2 urban, academic EDs. A 12-item survey was administered to a convenience sample of patients to assess for care satisfaction before, during, and after study interventions. Study interventions included (a) placement of branded folding seats and (b) an educational campaign. Only the intervention ED received folding seats. The primary outcome examined the influence of provider sitting on patient satisfaction. A secondary outcome examined the frequency of provider sitting. Results: During the entire study period, 2827 patients were surveyed; 63% were female and 65% were between the ages of 26 and 65. Sitting at any point during an ED encounter improved responses to satisfaction questions (polite [67% vs 59%], cared [64% vs 54%], listened [60% vs 52%], informed [57% vs 47%], time [56% vs 45%], P < .0001 for all measures). The odds of provider sitting increased 30% when a seat was placed in the room (odds ratio [OR] = 1.3, 95% confidence interval [CI]: 1.1-1.5). No change in provider sitting was observed in the control ED (OR = 1.0, 95% CI: 0.8-1.2). Conclusions: Placing a seat in a patient’s room nudges providers to sit during an ED encounter. Education alone did not influence provider behavior. Sitting down resulted in significantly higher patient satisfaction scores during an ED visit.

Soybean cyst nematode (Heterodera glycines Ichinohe) (SCN) is the most destructive pest affecting soybeans [Glycine max (L.) Merr.] in the U.S. To date, only two major SCN resistance alleles, rhg1 and Rhg4, identified in PI 88788 (rhg1) and Peking (rhg1/Rhg4), residing on chromosomes (Chr) 18 and 8, respectively, have been widely used to develop SCN resistant cultivars in the U.S. Thus, some SCN populations have evolved to overcome the PI 88788 and Peking derived resistance, making it a priority for breeders to identify new alleles and sources of SCN resistance. Toward that end, 461 soybean accessions from various origins were screened using a greenhouse SCN bioassay and genotyped with Illumina SoySNP50K iSelect BeadChips and three KASP SNP markers developed at the Rhg1 and Rhg4 loci to perform a genome-wide association study (GWAS) and a haplotype analysis at the Rhg1 and Rhg4 loci. In total, 35,820 SNPs were used for GWAS, which identified 12 SNPs at four genomic regions on Chrs 7, 8, 10, and 18 that were significantly associated with SCN resistance (P < 0.001). Of those, three SNPs were located at Rhg1 and Rhg4, and 24 predicted genes were found near the significant SNPs on Chrs 7 and 10. KASP SNP genotyping results of the 462 accessions at the Rhg1 and Rhg4 loci identified 30 that carried PI 88788-type resistance, 50 that carried Peking-type resistance, and 58 that carried neither the Peking-type nor the PI 88788-type resistance alleles, indicating they may possess novel SCN resistance alleles. By using two subsets of SNPs near the Rhg1 and Rhg4 loci obtained from SoySNP iSelect BeadChips, a haplotype analysis of 461 accessions grouped those 58 accessions differently from the accessions carrying Peking or PI 88788 derived resistance, thereby validating the genotyping results at Rhg1 and Rhg4. The significant SNPs, candidate genes, and newly characterized SCN resistant accessions will be beneficial for the development of DNA markers to be used for marker-assisted breeding and developing soybean cultivars carrying novel sources of SCN resistance.

Despite the importance of tree-thinking and evolutionary trees to biology, no appropriately developed concept inventory exists to measure student understanding of these important concepts. To address this need, we developed a multiple-choice concept inventory consisting of 24 pairs of items, and we provide evidence to support its use among undergraduate students. A set of learning outcomes was developed to guide the creation of the concept inventory. The learning outcomes, student interviews, and student responses were used to develop and revise inventory items. Supporting evidence was gathered from traditional item analysis, exploratory factor analysis, confirmatory factor analysis, traditional reliability analyses, and comparisons to alternative assessments. Appropriate implementation and utility of the concept inventory are discussed.

BackgroundPatients who undergo lumbar discectomy may experience ongoing lumbosacral radiculopathy (LSR) and seek spinal manipulative therapy (SMT) to manage these symptoms. We hypothesized that adults receiving SMT for LSR at least one year following lumbar discectomy would be less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT, over two years' follow-up.MethodsWe searched a United States network of health records (TriNetX, Inc.) for adults aged ≥ 18 years with LSR and lumbar discectomy ≥ 1 year previous, without lumbar fusion or instrumentation, from 2003 to 2023. We divided patients into two cohorts: (1) chiropractic SMT, and (2) usual care without chiropractic SMT. We used propensity matching to adjust for confounding variables associated with lumbar spine reoperation (e.g., age, body mass index, nicotine dependence), calculated risk ratios (RR), with 95% confidence intervals (CIs), and explored cumulative incidence of reoperation and the number of SMT follow-up visits.ResultsFollowing propensity matching there were 378 patients per cohort (mean age 61 years). Lumbar spine reoperation was less frequent in the SMT cohort compared to the usual care cohort (SMT: 7%; usual care: 13%), yielding an RR (95% CIs) of 0.55 (0.35-0.85; P = 0.0062). In the SMT cohort, 72% of patients had ≥ 1 follow-up SMT visit (median = 6).ConclusionsThis study found that adults experiencing LSR at least one year after lumbar discectomy who received SMT were less likely to undergo lumbar spine reoperation compared to matched controls not receiving SMT. While these findings hold promise for clinical implications, they should be corroborated by a prospective study including measures of pain, disability, and safety to confirm their relevance. We cannot exclude the possibility that our results stem from a generalized effect of engaging with a non-surgical clinician, a factor that may extend to related contexts such as physical therapy or acupuncture.RegistrationOpen Science Framework ( https://osf.io/vgrwz ).

Despite therapeutic advances, acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. One potential limitation of the current treatment paradigm is the lack of effective therapies to optimize reperfusion after ischemia and prevent reperfusion-mediated injury. Experimental studies indicate that this process accounts for up to 50% of the final infarct size, lending it importance as a potential target for cardioprotection. However, multiple therapeutic approaches have shown potential in pre-clinical and early phase trials but a paucity of clear clinical benefit when expanded to larger studies. Here we explore this history of trials and errors of the studies of cyclosporine A and other mitochondrial membrane permeability inhibitors, agents that appeared to have a promising pre-clinical record yet provided disappointing results in phase III clinical trials.

Summary: Activation of the TLR4 signaling pathway by lipopolysaccharide (LPS) leads to induction of both inflammatory and interferon-stimulated genes, but the mechanisms through which these coordinately activated transcriptional programs are balanced to promote an optimal innate immune response remain poorly understood. In a genome-wide small interfering RNA (siRNA) screen of the LPS-induced tumor necrosis factor α (TNF-α) response in macrophages, we identify the interferon-stimulated protein IFIT1 as a negative regulator of the inflammatory gene program. Transcriptional profiling further identifies a positive regulatory role for IFIT1 in type I interferon expression, implicating IFIT1 as a reciprocal modulator of LPS-induced gene classes. We demonstrate that these effects of IFIT1 are mediated through modulation of a Sin3A-HDAC2 transcriptional regulatory complex at LPS-induced gene loci. Beyond the well-studied role of cytosolic IFIT1 in restricting viral replication, our data demonstrate a function for nuclear IFIT1 in differential transcriptional regulation of separate branches of the LPS-induced gene program. : John et al. describe a function for IFIT1 in the innate immune response. Previously considered an antiviral protein, IFIT1 is identified as a reciprocal modulator of bacterially induced pro-inflammatory and interferon genes and shown to associate with chromatin regulators to modulate transcription and the host response to bacterial infection. Keywords: interferon, IFIT1, TLR4, interferon gene program, pro-inflammatory gene program, RNAi screen, TNF-α

Metabolomics is an effective approach to characterize the metabotype which can reflect the influence of genetics, physiological status, and environmental factors such as drug intakes, diet. Diet may change the chemopreventive efficacy of given agents due to the altered physiological status of the subject. Here, metabolomics response to a chemopreventive agent targretin or tamoxifen, in rats with methylnitrosourea-induced tumors on a standard diet (4% fat, CD) or a high fat diet (21% fat, HFD) was evaluated, and found that (1) the metabolome was substantially affected by diet and/or drug treatment; (2) multiple metabolites were identified as potential pharmacodynamic biomarkers related to targretin or tamoxifen regardless of diet and time; and (3) the primary bile acid pathway was significantly affected by targretin treatment in rats on both diets, and the lysolipid pathway was significantly affected by tamoxifen treatment in rats on the high fat diet.

Households consume a significant fraction of total potable water production. Strategies to improve the efficiency of water use tend to emphasize technological interventions to reduce or shift water demand. Behavioral water use reduction strategies can also play an important role, but a flexible framework for exploring the “what-ifs” has not been available. This paper introduces such a framework, presenting an agent-based model of household water-consuming behavior. The model simulates hourly water-using activities of household members within a rich technological and behavioral context, calibrated with appropriate data. Illustrative experiments compare the resulting water usage of U.S. and Dutch households and their associated water-using technologies, different household types (singles, families with children, and retired couples), different water metering regimes, and educational campaigns. All else equal, Dutch and metered households use less water. Retired households use more water because they are more often at home. Water-saving educational campaigns are effective for the part of the population that is receptive. Important interactions among these factors, both technological and behavioral, highlight the value of this framework for integrated analysis of the human-technology-water system.

The risk of quagga mussel (Dreissena rostriformis bugensis Andrusov 1897) establishment into water-bodies of the western US has expanded the geographic concern regarding the ecological and economic impacts this species will have in aquatic ecosystems. Thresholds based on calcium concentrations, an element critical for mussel growth and physiology, have been used as a primary predictor of quagga mussel establishment success to aid management decisions. We evaluated the invasion potential of quagga mussels in low calcium waters using laboratory experiments to compare the survival, growth and reproductive potential of adult mussels held for 90 days at low (9 and 12 ppm), moderate (15 to 32 ppm) and high (72 ppm) calcium water concentrations. In conjunction with adult experiments, veliger stage survival, growth and settlement were evaluated under similar low, moderate, and high calcium water treatments. Adult mussels survived, grew and showed reproductive potential in low calcium water (12 ppm). Veligers were also able to survive, grow and settle in low calcium water. Higher levels of natural seston biomass appeared to improve adult mussel life history performance in low calcium water. Survival curve analysis predicted that 99% adult mortality could occur in 15 ppm could have adults surviving more than a year. The results from these bioassays provide further evidence that quagga mussels have higher risk of establishment in low calcium lakes if habitats exist that have slightly elevated calcium. These results should help emphasize the vulnerability of water-body in the 12 to 15 ppm calcium range that could potentially be at risk of establishing sustainable quagga mussel populations. Furthermore, these results provide insights into the uncertainty of using a single parameter in assigning establishment risk given the complexity of variables in specific water-bodies that influence life history performance of introduced species.