24-hr Period Research Articles

Safety and pharmacokinetics of BXQ-350 in a phase 1a and 1b trial of solid tumors and high-grade glioma.

e13531 Background: BXQ-350 is composed of the multifunctional, lysosomal-activator protein Saposin C and phosphatidylserine lipid with demonstrated antitumor effects in vitro and in vivo. In this abstract we update the safety and pharmacokinetic (PK) profile based on an ongoing Phase 1 trial. Methods: BXQ-350 was administered in a Phase 1a dose-escalation trial (NCT02859857), and an ongoing Phase 1b trial (data cut off at max of 6 cycles, 01DEC2018) to refractory solid tumor/high-grade glioma patients (pts). In Phase 1a, pts received escalating IV BXQ-350 doses of 0.7, 1.1, 1.4, 1.8, or 2.4 mg/kg on days 1, 2, 3, 4, 5, 8, 10, 12, 15, 22 (cycle 1), 29 (cycle 2), and thereafter 28-day cycles. PK was assessed over a 24-hr period following the first dose. The Saposin C level was analyzed by ELISA and PK parameters were calculated using noncompartmental methods. Results: The 1a cohort of 18 pts (age 24-69) had a median of 3 cycles and 1b cohort of 20 pts (age 31-80) had median of 2 cycles with no treatment-related serious adverse events to date. Moderately severe related adverse events (AEs, n case, n events) are reported with serious non-related events. The most common treatment-related AE was fatigue (2 at dose 1.1, 2 at 1.8, 1 at 2.4mg/kg and 3 in 1b), at 2.4 mg/kg, 1 pt had moderate blood pressure elevation. Exposures in the 1.4 and 1.8 mg/kg cohorts were less than dose-proportional, likely due to higher clearance in those groups. The overall mean clearance and half-live values were 66.8 (mL/kg/h) and 4.03 h, respectively. Conclusions: BXQ-350 has had no serious related AEs during dose-escalation or in the on-going trial supporting a tolerable safety profile at 2.4 mg/kg. Clinical trial information: NCT02859857. [Table: see text]

DNA integrity and methylation changes of mouse spermatozoa following prolonged incubation.

Sperm quality can be affected by different factors including the length of incubation time between sperm preparation and intracytoplasmic sperm injection. Here, we have evaluated the level of DNA methylation and expressions of related genes in mice spermatozoa. The spermatozoa were divided into three groups: fresh, spermatozoa incubated at room temperature (RT) and 37°C for 24hr. The sperm chromatin structure assay was used to determine the DNA fragmentation index (DFI), and DNA methylation was analysed by flow cytometry. The expression levels of DNA methylation-related genes were determined by quantitative real-time PCR (qRT-PCR). According to the results, we observed significantly higher sperm progressive motility and viability in the group incubated at RT compared to the spermatozoa incubated at 37°C (p<0.05). Spermatozoa incubated at 37°C had a higher DFI compared to the other groups (p<0.05), but the DNA methylation level significantly decreased (p<0.05). qRT-PCR analysis showed increased Dnmt-1 expression in spermatozoa after 24-hr incubation at 37°C. However, there were significantly higher expression levels of Dnmt-3l, Dnmt-3a and Dnmt-3b after incubation at both RT and 37°C compared to the fresh group (p<0.05). The 24-hr incubation period affected both sperm DNA methylation and integrity. This study indicated that incubation at RT resulted in better sperm quality.

High-dynamic baseline determination for the Swarm constellation

Baseline determination for the European Space Agency Swarm magnetic field mission is investigated. Swarm consists of three identical satellites -A, -B and -C. The Swarm-A and -C form a pendulum formation whose baseline length varies between about 30 and 180 km. Swarm-B flies in a higher orbit, causing its orbital plane to slowly rotate with respect to those of Swarm-A and -C. This special geometry results in short periods when the Swarm-B satellite is adjacent to the other Swarm satellites. Ten 24-hr periods around such close encounters have been selected, with baseline lengths varying between 50 and 3500 km. All Swarm satellites carry high-quality, dual-frequency and identical Global Positioning System receivers not only allowing precise orbit determination of the single Swarm satellites, but also allowing a rigorous assessment of the capability of precise baseline determination between the three satellites. These baselines include the high-dynamic baselines between Swarm-B and the other two Swarm satellites.For all orbit determinations, use was made of an Iterative Extended Kalman Filter approach, which could run in single-, dual-, and triple-satellite mode. Results showed that resolving the issue of half-cycle carrier phase ambiguities (present in original release of GPS RINEX data) and reducing the code observation noise by the German Space Operations Center converter improved the consistency of reduced-dynamic and kinematic baseline solutions for both the Swarm-A/C pendulum pair and other combinations of Swarm satellites. All modes led to comparable consistencies between the computed orbit solutions and satellite laser ranging observations at a level of 2 cm. In addition, the consistencies with single-satellite ambiguity fixed orbit solutions by the German Space Operations Center are at comparable levels for all the modes, with reduced-dynamic baseline consistency at a level of 1-3 mm for the pendulum Swarm-A/C formation and 3-5 mm for the high-dynamic Swarm-B/A and -B/C satellite pairs in different directions.

Imminent Aggression in Female Forensic Inpatients: A Study Assessing the Predictive Validity of the Dynamic Appraisal of Situational Aggression: Women’s Version (DASA: WV)

Despite high rates of aggression on female psychiatric inpatient units and research to suggest that risk factors for violence may be different for men and women, violence risk assessment instruments are typically developed and validated through research on male populations. The current study tested a female-specific modification to an existing risk assessment instrument, the Dynamic Appraisal of Situational Aggression: Women’s Version (DASA:WV). The modification involved addition of two factors taken from the Female Additional Manual used in conjunction with the HCR-20 (Covert/Manipulative Behaviour and Low Self-Esteem) and a rating of ward atmosphere to the original DASA. Nursing staff on a high secure female forensic unit rated patients on the DASA:WV at the end of each shift and recorded incidents of verbal aggression and physical aggression against others, objects, and self in the subsequent 24-hr period. Hierarchical (multilevel) logistic regression was employed in the statistical analysis to account for the incorporation of multiple repeated measures for each participant. While the evidence for the predictive validity of the DASA for aggression in a female forensic population was strengthened, the hypothesis that the DASA:WV would significantly improve predictive validity for female patients was not supported.

Movement ecology and stenothermy of satellite-tagged shortbill spearfish (Tetrapturus angustirostris)

The shortbill spearfish (Tetrapturus angustirostris) is an understudied, istiophorid billfish primarily encountered as bycatch in pelagic commercial fisheries of the Indo-Pacific. The species is listed as data-deficient, and little is known of its biology, ecology, and population structure or status. We assessed the species’ movement ecology and thermal niche with telemetry data from the first shortbill spearfishes ever outfitted with pop-up satellite archival transmitting tags (n = 3 with successfully transmitted data). Short (4–15 day) deployments offshore of the Island of Hawai’i revealed that spearfish primarily occupied the mixed layer, spending >90% of each 24-hr period between the surface and 100 m in water temperatures between 24–26 °C. These individuals consistently exhibited vertical activity at night regardless of the prevailing lunar phase. Nocturnal movements throughout the mixed layer may enable shortbill spearfish to forage on mesopelagic species undergoing diel vertical migration and reduce trophic niche overlap with primarily diurnal, pelagic species. The narrow thermal distribution of shortbill spearfish in this study, almost exclusively within 2 °C of sea surface temperature, suggests that they are more stenothermal than extra-generic istiophorid species.

Measuring Reliability of Movement With Accelerometry: Fitbit® Versus ActiGraph®.

We sought to determine the reliability of the Fitbit® Flex™ compared with the ActiGraph® Bluetooth® Smart wGT3X-BT wireless activity monitor and to contribute to the clinical utility of accelerometry measurement of upper extremity (UE) movement. Two studies were conducted at different sites with healthy adult participants. In Study 1, participants wore both accelerometers on both wrists during everyday activities for a 24-hr period. In Study 2, participants wore both accelerometers on the dominant wrist for 4 hr during an active period of the day. All participants wore the accelerometers during regular daily activities. Data recorded from the Fitbit and the ActiGraph showed a high positive correlation; however, the Fitbit recorded significantly fewer movements than the ActiGraph. Although the Fitbit and the ActiGraph measure UE activity similarly, the Fitbit was not as sensitive as the ActiGraph. This study provides informative data on the clinical utility of the Fitbit compared with the ActiGraph.

Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of α6 GABAA receptors.

γ-Aminobutyric acid type A (GABAA ) receptors containing the α6 subunit are located in trigeminal ganglia, and their reduction by small interfering RNA increases inflammatory temporomandibular and myofascial pain in rats. We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK-I-56-1 at concentrations below 1µM enhanced γ-aminobutyric acid (GABA) currents at recombinant rat α6β3γ2, α6β3δ and α6β3 receptors, whereas it was inactive at most GABAA receptor subtypes containing other α subunits. DK-I-87-1 at concentrations below 1µM was inactive at α6-containing receptors and only weakly modulated other GABAA receptors investigated. Both plasma and brain tissue kinetics of DK-I-56-1 were relatively slow, with half-lives of 6 and 13hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10-300nM throughout a 24-hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK-I-56-1 during 14days after surgery or with DK-I-56-1 or DK-I-87-1 during 14days after trigeminal neuropathy were already established, demonstrated that DK-I-56-1 but not DK-I-87-1 significantly reduced the hypersensitivity response to von Frey filaments. SIGNIFICANCE: Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK-I-56-1 that positively modulates α6 GABAA receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.

Noise at sea: Characterization of extended shift noise exposures among U.S. Navy aircraft carrier support personnel

The purpose of this investigation was to characterize 12-hr on-duty, 12-hr off-duty, and 24-hr noise exposures among U.S. Navy aircraft carrier support personnel. Noise dosimetry samples were collected for 47 aircraft carrier support personnel while at sea during airwing carrier qualifications. Leq measurements during 12-hr on-duty, 12-hr off-duty, and over 24-hr periods were compared to Threshold Limit Values. Four similar exposure groups (SEGs) were created based upon departmental assignment and similarity of work tasks: (1) Administration/Religious Ministries/Legal/Training, (2) Combat Systems/Operations, (3) Medical/Dental, and (4) Supply. Equivalent sound level (Leq) measurements in decibels “A” weighted (dBA) were compared to determine significant differences between each group according to 12-hr on-duty, 12-hr off-duty, and 24-hr periods. Mean 24-hr noise levels ranged from 69–88 dBA with 22% exceeding the 80 dBA Threshold Limit Value. Twelve-hr on-duty noise levels ranged from 71–90 dBA with 17% exceeding the 83 dBA 12-hr on-duty Threshold Limit Value. Twelve-hr off-duty noise exposure ranged from 68–84 dBA with 95% exceeding the 70 dBA American Conference of Governmental Industrial Hygienists threshold classified as effective quiet to allow for temporary threshold shift recovery. Welch Analysis of Variance and Dunnett T3 post hoc tests revealed SEG 2 had significantly higher 24-hr noise exposures than SEG 3 (p = 0.019) and SEG 4 (p = 0.045). SEG 2 had significantly higher 12-hr on-duty noise exposure than SEG 3 (p = 0.030). One Way Analysis of Variance revealed no significant differences between 12-hr off-duty noise exposures according to SEG (p = .096). Some aircraft carrier support personnel had 12-hr on-duty and 24-hr noise exposures exceeding Threshold Limit Values with a large proportion exceeding the 70 dBA effective quiet limit during 12-hr off-duty periods. Results suggest personnel that are typically considered low risk for hazardous noise exposure (<85 dBA) during 8-hr shifts may have a greater risk of noise exposure when considering full 12-hr and 24-hr shifts when working and living in close proximity.

Native lagomorphs suppress grass establishment in a shrub-encroached, semiarid grassland.

Shrub encroachment into arid grasslands has been associated with reduced grass abundance, increased soil erosion, and local declines in biodiversity. Livestock overgrazing and the associated reduction of fine fuels has been a primary driver of shrub encroachment in the southwestern United States, but shrublands continue to persist despite livestock removal and grassland restoration efforts. We hypothesized that an herbivory feedback from native mammals may contribute to continued suppression of grasses after the removal of livestock. Our herbivore exclusion experiment in southeastern Arizona included five treatment levels and allowed access to native mammals based on their relative body size, separating the effects of rodents, lagomorphs, and mule deer. We included two control treatments and replicated each treatment 10 times (n = 50). We introduced uniform divisions of lawn sod (Cynodon dactylon) into each exclosure for 24‐hr periods prior to (n = 2) and following (n = 2) the monsoon rains and used motion‐activated cameras to document herbivore visitations. In the pre‐monsoon trials, treatments that allowed lagomorph access had less sod biomass relative to other treatments (p < 0.001), averaging 44% (SD 36%) and 29% (SD 45%) remaining biomass after the 24‐hr trial periods. Following the onset of monsoons, differences in remaining biomass among treatments disappeared. Desert cottontails (Sylvilagus audubonii) were detected more frequently than any of the other 11 herbivore species present at the site, accounting for 83% of detections during the pre‐monsoon trials. Significantly more (p < 0.001) desert cottontails were detected during the pre‐monsoon trials (2,077) compared to the post‐monsoon trials (174), which coincided with biomass removal from lagomorph accessible treatments. We conclude that desert cottontails are significant consumers of herbaceous vegetation in shrub‐encroached arid grasslands and they, along with other native herbivores, may act as a biotic feedback contributing to the competitive advantage and persistence of shrubs.

An RpaA-Dependent Sigma Factor Cascade Sets the Timing of Circadian Transcriptional Rhythms in Synechococcus elongatus

The circadian clock of the cyanobacterium Synechococcus elongatus PCC 7942 drives oscillations in global mRNA abundances with 24-hr periodicity under constant light conditions. The circadian clock-regulated transcription factor RpaA controls the timing of circadian gene expression, but the mechanisms underlying this control are not well understood. Here, we show that four RpaA-dependent sigma factors-RpoD2, RpoD6, RpoD5, and SigF2-are sequentially activated downstream of active RpaA and are required for proper expression of circadian mRNAs. By measuring global gene expression in strains modified to individually lack rpoD2, rpoD6, rpoD5, and sigF2, we identify how expression of circadian mRNAs, including sigma factor mRNAs, is altered in the absence of each sigma factor. Broadly, our findings suggest that a single transcription factor, RpaA, is sufficient to generate complex circadian expression patterns in part by regulating an interdependent sigma factor cascade.

Capturing patients' symptom expression and spouses' cardiovascular responses continuously: The feasibility of examining a mechanism of disease risk in the home.

Spousal caregivers face increased cardiovascular risks; lab studies suggest that autonomic reactivity to patients' physical suffering may play a role. To evaluate this mechanism in daily life, our pilot study characterized the feasibility of recruiting couples for a multimethod, in-home assessment. We examined the usability of the resulting data in an effort to link spousal cardiovascular changes to patient pain expression during couples' everyday interactions. For two 48-hr periods, individuals with rheumatoid arthritis (RA) and their partners wore heart monitors while audio-recordings captured couples' in-home interactions. Interbeat intervals were subsetted in 1-, 2-, and 5-min windows before and after each pain expression. Pre-post difference scores in high-frequency heart rate variability (HF-HRV) and heart rate were examined. Of the 17 screened RA patients, 11 were ineligible, and 3 partners declined. The 3 participating couples completed all study activities. The resulting 288 hr of recordings were coded for patients' RA symptom expression, which varied from none to an average of 11 times daily. One couple had sufficient data for physiological analysis: Contrary to prediction, spouse HF-HRV significantly increased after patient symptom expression. Recruitment rates mirrored other couples studies, and enrolled couples complied with study procedures. In-home conversations were reliably coded and successfully linked to spousal ongoing cardiovascular activity. Preliminary findings highlight the importance of optimal sampling windows and suggest symptom expression as a relevant process for some spouses but not others. We offer recommendations for efficiently scaling up the method in future studies. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Ultradian Rhythms in the Transcriptome of Neurospora crassa

SummaryIn many organisms, the circadian clock drives rhythms in the transcription of clock-controlled genes that can be either circadian (∼24-hr period) or ultradian (<24-hr period). Ultradian rhythms with periods that are a fraction of 24 hr are termed harmonics. Several harmonic transcripts were discovered in the mouse liver, but their functional significance remains unclear. Using a model-based analysis, we report for the first time ∼7-hr third harmonic transcripts in Neurospora crassa, a well-established fungal circadian model organism. Several third harmonic genes are regulated by female fertility 7 (FF-7), whose transcript itself is third harmonic. The knockout of circadian output regulator CSP1 superimposes circadian rhythms on the third harmonic genes, whereas the knockout of stress response regulator MSN1 converts third harmonic rhythms to second harmonic rhythms. The 460 ∼7-hr genes are co-regulated in two anti-phasic groups in multiple genotypes and include kinases, chromatin remodelers, and homologs of harmonic genes in the mouse liver.

Pure-Air: A Global Assessment of Household and Outdoor Air Pollution and Cardiopulmonary Disease

We are adding an air pollution study (PURE-AIR) to the ongoing prospective urban and rural epidemiological (PURE) cohort, which includes ~225,000 adults aged 35-70 years living in 850 communities in 27 countries. Here, we will describe the comprehensive methods used to estimate outdoor, household and personal air pollution exposures. Outdoor estimates include PM2.5, from an existing 1x1km satellite surface, and NO2, from a newly created global LUR model. In addition, we are measuring PM2.5 for 48-hr periods using the UPAS monitor in ~4,500 households and concurrently for ~1,200 individuals. Individuals also wear a silicon wristband to capture organic exposures. To-date we have collected data for 1,400 households and 300 individuals. Data collection will continue for the next 18 months. Preliminary outdoor, household and individual exposure assessment results will be presented and future plans for epidemiological analyses.

The Influence of Side Effect Information Framing on Nocebo Effects.

One contributing factor to the development of nocebo effects is information provided about possible side effects. However, nondisclosure of information can be problematic. We assessed whether positively framed side effect information (highlighting likelihood of not experiencing side effects) can reduce nocebo effects compared to negatively framed information (highlighting likelihood of experiencing side effects). One hundred twelve participants took part in research ostensibly assessing the influence of benzodiazepines (actually sham capsules) on anxiety. Participants were randomized to receive a sham capsule with positively or negatively framed information about four side effects, or a no-treatment control condition. Side effect expectations were assessed after information provision. Framed side effects and other unmentioned symptoms were assessed during the session and 24-hr follow-up. Nocebo effects occurred in symptoms presented as side effects (regardless of framing) during the study session and follow-up (ps < .003). At follow-up, there was also a nocebo effect in other unmentioned symptoms (p = .018). Positive framing reduced side effect symptoms compared with negative framing during the study session (p = .037), but this effect was no longer present at follow-up (p = .53). Side effect expectations did not differ between the framing conditions (p = .14). Positive framing reduced side effects short-term, but not at follow-up. Expectations did not differ between negative and positive framing. Nocebo effects appeared to generalize to other unmentioned symptoms over a 24-hr period. Further research is needed to determine whether the initial impact of positive framing can be maintained over time.

Intestinal Metabolism and Bioaccumulation of Sucralose In Adipose Tissue In The Rat

ABSTRACTThe aim of this study was to (1) determine if the organochlorine artificial sweetener sucralose is metabolized in rat intestine with repeated dosing and (2) examine whether sucralose might bioaccumulate in rat adipose tissue. Sucralose was administered to 10 rats by gavage daily for 40 days at an average dosage of 80.4 mg/kg/day. The dosages were within the range utilized in historical toxicology studies submitted for regulatory approval in North America, Europe, and Asia. Feces and urine were collected individually from each animal for every 24-hr period during the 40-day dosing period. Analysis of the urine and fecal extracts by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS) revealed two new biotransformation products that have not previously been reported. These two metabolites are both acetylated forms of sucralose that are less polar and hence more lipophilic than sucralose itself. These metabolites were present in urine and feces throughout the sucralose dosing period and still detected at low levels in the urine 11 days after discontinuation of sucralose administration and 6 days after sucralose was no longer detected in the urine or feces. The finding of acetylated sucralose metabolites in urine and feces do not support early metabolism studies, on which regulatory approval was based, that claimed ingested sucralose is excreted unchanged (i.e. not metabolized). The historical metabolic studies apparently failed to detect these metabolites in part because investigators used a methanol fraction from feces for analysis along with thin layer chromatography and a low-resolution linear radioactivity analyzer. Further, sucralose was found in adipose tissue in rats two weeks after cessation of the 40-day feeding period even though this compound had disappeared from the urine and feces. Thus, depuration of sucralose which accumulated in fatty tissue requires an extended period of time after discontinuation of chemical ingestion. These new findings of metabolism of sucralose in the gastrointestinal tract (GIT) and its accumulation in adipose tissue were not part of the original regulatory decision process for this agent and indicate that it now may be time to revisit the safety and regulatory status of this organochlorine artificial sweetener

Collector characterisation and heat loss tests on a novel batch solar water heater with CPC reflector for households

ABSTRACTThis solar water-heating unit is an integration of the older concept of batch water heating with the modern trends in solar water-heating technologies i.e. incorporating a concentrator in the design. The concentrator used is the compound parabolic type (CPC) which is a non-imaging device having wider acceptance angle (64°) and supported on a wooden cradle, which comprises the two arms of the parabola. To suppress the heat loss, an air gap has been introduced in the arms of the CPC. The collector is a single larger diameter drum which serves both as an absorber and storage unit positioned at the focus of CPC. The parametric study of the model showed the thermal efficiency of the collector as high as 38% and maximum water temperature attained was 53°C. Heat loss tests performed on the collector on a 24-hr cycle period showed good long time performance estimates. The response time of collector computed and performance characteristic curve plotted to predict system response under any given conditions of solar insolation and ambient temperature.

The French Emergency National Survey: A description of emergency departments and patients in France.

IntroductionSome major changes have occurred in emergency department (ED) organization since the early 2000s, such as the establishment of triage nurses and short-track systems. The objectives of this study were to describe the characteristics of French EDs organization and users, based on a nationwide cross-sectional survey.MethodsThe French Emergency Survey was a nationwide cross-sectional survey. All patients presenting to all EDs during a 24-hr period of June 2013 were included. Data collection concerned ED characteristics as well as patient characteristics.ResultsAmong the 736 EDs in France, 734 were surveyed. Triage nurses and short-track systems were respectively implemented in 73% and 41% of general EDs. The median proportion of patients aged > 75 years was 14% and median hospitalisation rate was 20%. During the study period, 48,711 patients presented to one of the 734 EDs surveyed. Among them, 7% reported having no supplementary health or universal coverage (for people with lower incomes). Overall, 50% of adult patients had been seen by the triage nurse in less than 5 minutes, 74% had a time to first medical contact shorter than one hour and 55% had an ED length of stay shorter than 3 hours.ConclusionThe French Emergency Survey is the first study to provide data on almost all EDs in France. It underlines how ED organization has been redesigned to face the increase in the annual census. French EDs appear to have a particular role for vulnerable people: age-related vulnerability and socio-economic vulnerability with an over-representation of patients without complementary health coverage.

Analysis of Fecal Primary Bile Acids Detects Increased Stool Weight and Colonic Transit in Patients With Chronic Functional Diarrhea

Patients with bile acid diarrhea (BAD) are identified based on increased levels of BAs in fecal samples collected over a 48-hr period while on a 100-gram fat diet (48-hr BA), retention of 75Se-labeled homocholic acid taurine, or serum levels of C4 or FGF19. BAD increases fecal weight and colonic transit. We investigated whether results of tests for BAD associate with increased fecal weight and more rapid colonic transit over a 24- or 48-hr period in patients with irritable bowel syndrome with diarrhea (IBS-D). We also estimated the prevalence of increased 48-hr fecal BAs in patients with chronic diarrhea. We performed a retrospective study of 64 patients with IBS-D, 30 patients with IBS-constipation, 30 healthy volunteers (controls). We collected data on fecal weights (measured over a 48-hr period), colonic transit over a 24-hr period (measured by scintigraphy), and percentages of different BAs in stool samples. Colonic transit was measured as the geometric center (weighted average) of colonic counts on a scale of 1 (100% in ascending colon) to 5 (100% in stool). We performed area under the curve (AUC) analyses to assess theassociation between result of serum and stool tests and high fecal weight (>400g/48 hrs) or rapid colonic transit (>3.34, corresponding to isotope geometric center in sigmoid colon). We estimated the prevalence of increased 48-hr fecal BAs among 938 patients with chronic diarrhea. Total fecal 48-hr BA alone, or in combination with percentage of primary fecal BAs, identified patients with increased fecal weight with an AUROC of 0.86. Percentage of primary fecal BA alone identified patients with increased fecal weight with an AUROC of 0.73. Total fecal 48-hr BA alone identified patients with increased colonic transit with an AUROC of 0.65 and percentage of primary fecal BA alone identified patients with increased colonic transit with an AUROC of 0.69; combined data on these features identified patients with increased colonic transit with an AUROC of 0.70. Serum level of C4 identified patients with increased colonic transit with an AUROC of 0.60. Primary BAs >10% identified patients with increased fecal weight (sensitivity 49% and specificity 91%) and rapid colonic transit (sensitivity 48% and specificity 87%). Among the patients with chronic diarrhea, 45.6% had fecal primary BAs >10% and 27% had increased total fecal BAs (>2337 μmol/48 hrs). In a retrospective analysis of patients with IBS-D, we found percentage of primary BAs in fecal samples to provide an alternative to total fecal BAs in identification of patients with BAD or chronic diarrhea.

The Effect of Various Police Enforcement Actions on Violent Crime: Evidence From a Saturation Foot-Patrol Intervention

The current study tests the crime prevention effect of different police actions conducted during a foot-patrol saturation initiative in Newark, New Jersey. Police actions were categorized into two typologies: enforcement actions (i.e., arrests, quality of life summonses and field interrogations) and guardian actions (i.e., business checks, citizen contacts, bus checks, and taxi inspections). Logistic regression models tested the effect of enforcement and guardian actions on crime during daily (i.e., 24-hr) periods as well as the intervention’s operational (6:00 p.m.-2:00 a.m.) and nonoperational (2:00 a.m.-5:00 p.m.) periods. Analyses were conducted twice, once for the Operation Impact target area and once for a surrounding catchment zone (to measure spatial displacement). Findings suggest that guardian actions had a greater crime prevention effect than enforcement actions on crime occurrence. Policy implications of the findings are discussed.

Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative Stress Even without Weight Loss in Men with Prediabetes

Intermittent fasting (IF) improves cardiometabolic health; however, it is unknown whether these effects are due solely to weight loss. We conducted the first supervised controlled feeding trial to test whether IF has benefits independent of weight loss by feeding participants enough food to maintain their weight. Our proof-of-concept study also constitutes the first trial of early time-restricted feeding (eTRF), a form of IF that involves eating early in the day to be in alignment with circadian rhythms in metabolism. Men with prediabetes were randomized to eTRF (6-hr feeding period, with dinner before 3 p.m.) or a control schedule (12-hr feeding period) for 5weeks and later crossed over to the other schedule. eTRF improved insulin sensitivity, β cell responsiveness, blood pressure, oxidative stress, and appetite. We demonstrate for the first time in humans that eTRF improves some aspects of cardiometabolic health and that IF's effects are not solely due to weight loss.