Synthesis of Aryl Ketoamides via Aryne Insertion into Imides

An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines

Consumer perspectives on acceptability of trauma-focused cognitive behavioral therapy in Tanzania and Kenya: A mixed methods study

Background There is a substantial mental health treatment gap globally. Increasingly, mental health treatments with evidence of effectiveness in western countries have been adapted and tested in culturally and contextually distinct countries. Findings from these studies have been promising, but to better understand treatment outcome results and consider broader scale up, treatment acceptability needs to be assessed and better understood. This mixed methods study aimed to examine child and guardian acceptability of trauma-focused cognitive behavioral therapy (TF-CBT) in two regions in Tanzania and Kenya and to better understand how TF-CBT was perceived as helpful for children and guardians. Methods Participants were 315 children (7–13), who experienced the death of one or both parents and 315 guardians, both of whom participated in TF-CBT as part of a randomized controlled trial conducted in Tanzania and Kenya. The study used mixed methods, with quantitative evaluation from guardian perspective (N=315) using the Treatment Acceptability Questionnaire (TAQ) and the Client Satisfaction Questionnaire-8 (CSQ-8). Acceptability was assessed qualitatively from both guardian and child perspectives. Qualitative evaluation involved analysis using stratified selection to identify 160 child and 160 guardian interviews, to allow exploration of potential differences in acceptability by country, setting (urban/rural), and youth age (younger/older). Results Guardians reported high acceptability on the TAQ and, using an interpretation guide from U.S.-based work, medium acceptability on the CSQ-8. Guardians and children noted high acceptability in the qualitative analysis, noting benefits that correspond to TF-CBT’s therapeutic goals. Analyses exploring differences in acceptability yielded few differences by setting or child age but suggested some potential differences by country. Conclusion Quantitative and qualitative data converged to suggest high acceptability of TF-CBT from guardian and child perspectives in Tanzania and Kenya. Findings add to accumulating evidence of high TF-CBT acceptability from Zambia and other countries (United States, Norway, Australia). Plain Language Summary: Evidence-based treatments have been shown to be effective in countries and regions that are contextually and culturally distinct from where they were developed. But, perspectives of consumers on these treatments have not been assessed regularly or thoroughly. We used open-ended questions and rating scales to assess guardian and youth perspectives on a group-based, cognitive behavioral treatment for children impacted by parental death, in regions within Tanzania and Kenya. Our findings indicate that both guardians and youth found the treatment to be very acceptable. Nearly all guardians talked about specific benefits for the child, followed by benefits for the family and themselves. Eighty percent of youth mentioned benefits for themselves and all youth said they would recommend the program to others. Benefits mentioned by guardians and youth corresponded to treatment goals (improved mood/feelings or behavior, less distress when thinking about the parent/s’ death). Both guardians and children named specific aspects of the treatment that they liked and found useful. Dislikes and challenges of the treatment were less frequently mentioned, but point to areas where acceptability could be further improved. Recommendations from participants also offer areas where acceptability could be improved, namely guardians’ recommendation that the treatment also address non-mental health needs and offer some follow-up or opportunity to participate in the program again. Our study provides an example of how to assess acceptability and identify places to further enhance acceptability

Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs

African smoke particles act as cloud condensation nuclei in the wintertime tropical North Atlantic boundary layer over Barbados

The number concentration and properties of aerosol particles serving as cloud condensation nuclei (CCN) are important for understanding cloud properties, including in the tropical Atlantic marine boundary layer (MBL), where marine cumulus clouds reflect incoming solar radiation and obscure the low-albedo ocean surface. Studies linking aerosol source, composition, and water uptake properties in this region have been conducted primarily during the summertime dust transport season, despite the region receiving a variety of aerosol particle types throughout the year. In this study, we compare size-resolved aerosol chemical composition data to the hygroscopicity parameter κ derived from size-resolved CCN measurements made during the Elucidating the Role of Clouds–Circulation Coupling in Climate (EUREC4A) and Atlantic Tradewind Ocean-Atmosphere Mesoscale Interaction Campaign (ATOMIC) campaigns from January to February 2020. We observed unexpected periods of wintertime long-range transport of African smoke and dust to Barbados. During these periods, the accumulation-mode aerosol particle and CCN number concentrations as well as the proportions of dust and smoke particles increased, whereas the average κ slightly decreased (κ=0.46±0.10) from marine background conditions (κ=0.52±0.09) when the submicron particles were mostly composed of marine organics and sulfate. Size-resolved chemical analysis shows that smoke particles were the major contributor to the accumulation mode during long-range transport events, indicating that smoke is mainly responsible for the observed increase in CCN number concentrations. Earlier studies conducted at Barbados have mostly focused on the role of dust on CCN, but our results show that aerosol hygroscopicity and CCN number concentrations during wintertime long-range transport events over the tropical North Atlantic are also affected by African smoke. Our findings highlight the importance of African smoke for atmospheric processes and cloud formation over the Caribbean.</p

Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype

The Lnk adapter protein negatively regulates the signaling of thrombopoietin (TPO), the main megakaryocyte (MK) growth factor. Lnk-deficient (-/-) mice have increased TPO signaling and increased MK number. Interestingly, several mouse models exist in which increased MK number leads to a high bone mass phenotype. Here we report the bone phenotype of these mice. MicroCT and static histomorphometric analyses at 20 weeks showed the distal femur of Lnk-/- mice to have significantly higher bone volume fraction and trabecular number compared to wild-type (WT) mice. Notably, despite a significant increase in the number of osteoclasts (OC), and decreased bone formation rate in Lnk-/- mice compared to WT mice, Lnk-/- mice demonstrated a 2.5-fold greater BV/TV suggesting impaired OC function in vivo. Additionally, Lnk-/- mouse femurs exhibited non-significant increases in mid-shaft cross-sectional area, yet increased periosteal BFR compared to WT femurs was observed. Lnk-/- femurs also had non-significant increases in polar moment of inertia and decreased cortical bone area and thickness, resulting in reduced bone stiffness, modulus, and strength compared to WT femurs. Of note, Lnk is expressed by OC lineage cells and when Lnk-/- OC progenitors are cultured in the presence of TPO, significantly more OC are observed than in WT cultures. Lnk is also expressed in osteoblast (OB) cells and in vitro reduced alkaline phosphatase activity was observed in Lnk-/- cultures. These data suggest that both direct effects on OB and OC as well as indirect effects of MK in regulating OB contributes to the observed high bone mass. J. Cell. Biochem. 118: 2231-2240, 2017

Effects of Dietary Amino Acid Density and Exogenous Protease Inclusion on Growth Performance and Apparent Ileal Amino Acid Digestibility in Turkeys

Protein is one of the most expensive nutrients in poultry diets. In an effort to minimize feed costs, protein digestion and utilization by the animal must be carried out as effi­ciently as possible. The objective of this experiment was to evaluate the effects of dietary amino acid density and exogenous protease inclusion on growth performance and amino acid digestibility in turkey poults. Hybrid turkey poults (n = 780) were fed diets formulated to provide low (LAA) or adequate (AAA) amino acid density (approxi­mately 91 and 100% of the NRC4 recommended requirement for digestible Lys, respec­tively) with each diet being fed with or without an exogenous protease. Poults received experimental diets from d 1 to 42 of age. Growth performance metrics were calculated from pen weights and feed consumption was recorded throughout each experiment, and digestibility data were obtained from analysis of ileal contents. Data were analyzed using SAS 9.4 with pen as the experimental unit and pen location as the blocking factor. For the overall experiment (d 0 to 42), poults fed AAA diets had improved (P \u3c 0.01) ADG, ADFI, and feed conversion ratio (FCR) compared to those fed LAA diets. There was no difference (P \u3e 0.14) in poult performance due to protease inclusion. There was an amino acid density × protease interaction (P = 0.01) for apparent ileal amino acid digestibility (AIAAD) of Trp. There was no difference in AIAAD coefficients of Trp in the LAA diets with or without protease. However, in the AAA diets, poults not receiving protease had greater AIAAD of Trp than those consuming protease. There was no difference (P \u3e 0.09) in AIAAD coefficients of Arg, Met, Cys, Thr, Ile, Leu, Lys, or Val due to dietary amino acid density or protease inclusion. Greater amino acid density improved growth performance in poults up to 42 d of age. No improvement in growth performance was observed when poults were fed an exogenous protease in the starter phase, although protease inclusion increased ADG by 5.3% and ADFI by 4.1% during the grower phase. There was no benefit of increased dietary amino acid density or protease inclusion on AIAAD in poults

BioTIME: A database of biodiversity time series for the Anthropocene.

MotivationThe BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.Main types of variables includedThe database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.Spatial location and grainBioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).Time period and grainBioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.Major taxa and level of measurementBioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.Software format.csv and .SQL

Timing of decompression in patients with acute spinal cord injury: a systematic review

Study Design: Systematic review. Objective: To conduct a systematic review and synthesis of the literature to assess the comparative effectiveness, safety, and cost-effectiveness of early (24 hours) in adults with acute spinal cord injury (SCI). Methods: A systematic search was conducted of Medline, EMBASE, the Cochrane Collaboration Library, and Google Scholar to identify studies published through November 6, 2014. Studies published in any language, in humans, and with an abstract were considered for inclusion. Included studies were critically appraised and the overall strength of evidence was determined using methods proposed by the Grading of Recommendation Assessment, Development and Evaluation working group. Results: The search yielded 449 potentially relevant citations. Sixteen additional primary studies were identified through other sources. Six studies met inclusion criteria. All but 2 studies were considered to have moderately high risk of bias. Across studies and injury levels, the impact of early surgical decompression (<= 24 hours) on clinically important improvement in neurological status was variable. Isolated studies reported statistically significant and clinically important improvements at 6 months (cervical injury, low strength of evidence) and following discharge from inpatient rehabilitation (all levels, very low strength of evidence) but not at other time points; another study observed a statistically significant 6 point improvement in ASIA Impairment Scale (AIS) among patients with AIS B, C, or D, but not for those with AIS A (very low strength of evidence). In one study of acute central cord syndrome without instability, a clinically and statistically meaningful improvement in total motor scores was reported at 6 and 12 months in patients treated early (versus late). There were, however, no significant differences in AIS improvement between early and late surgical groups at 6- or 12-months (very low strength of evidence). One of 3 studies found a shorter length of hospital stay associated with early surgical decompression. Of 3 studies reporting on safety, no significant differences in rates of complications (including mortality, neurologic deterioration, pneumonia or pressure ulcers) were noted between early and late decompression groups. Conclusions: Results surrounding the efficacy of early versus late decompressive surgery, as well as the quality of evidence available, were variable depending on the level of SCI, timing of follow-up, and specific outcome considered. Existing evidence supports improved neurological recovery among cervical SCI patients undergoing early surgery; however, evidence regarding remaining SCI populations and clinical outcomes was inconsistent

Effects of Dietary Amino Acid Density and Exogenous Protease Inclusion on Growth Performance and Apparent Ileal AA Digestibility in Broilers

Protein is one of the most expensive nutrients in poultry diets. In an effort to minimize feed costs, protein digestion and utilization by the animal must be carried out as efficiently as possible. Therefore, the objective of this study was to evaluate the effects of dietary AA density and exogenous protease inclusion on growth performance and AA digestibility in broilers. Treatments consisted of a 2 × 4 factorial design with main effects of commercial protease (with or without) and digestible Lys (1.12, 1.15, 1.18, or 1.21%). Broiler chicks were housed in 4 Petersime batteries and treatments were randomly assigned to 80 cages within location block, resulting in 10 cages per treatment with 6 chicks per cage at placement. A commercial enzyme complex with 3 proteolytic activities was added to the protease diets at 0.25 lb/ton, and the same inclusion of sand was added to the diets without protease. Diets were balanced by energy and Lys:amino acid ratios. Titanium dioxide was included in the diets at 0.5% as an indigestible marker. On d 20, ileal contents from 2 chicks per cage were collected and composited by cage for calculation of apparent ileal AA digestibility. Growth performance metrics were calculated from cage weights and feed consumption was recorded throughout the experiment, and AA digestibility data were obtained from analysis of ileal contents. Data were analyzed using SAS 9.4 with cage as the experimental unit and cage location as the blocking factor. There was no evidence of an amino acid density × protease interaction (P \u3e 0.05) for BW, ADG or ADFI. There was an amino acid density × protease interaction (quadratic, P \u3c 0.05) for feed conversion ratio (FCR). Chicks fed 1.12 and 1.21% digestible Lys diets with added protease had a 2-point improvement in FCR compared to chicks fed these diets without protease. There was no difference in FCR between birds consuming diets with or without protease when fed 1.15 and 1.18% digestible Lys diets. There was no evidence of difference (P \u3e 0.10) in ADG or ADFI due to dietary amino acid density throughout the feeding period. However, broiler FCR was improved (linear, P \u3c 0.01) by increasing dietary amino acid density from 1.12 to 1.21% digestible Lys. There was no evidence (P \u3e 0.10) of main effect of added protease on BW, ADG, ADFI, or FCR. There was not an amino acid density × protease interaction (P \u3e 0.09) or main effect of dietary amino acid density or protease inclusion (P \u3e 0.12) on apparent ileal digestibility (AID) of Lys, Arg, Met, Cys, Thr, Ile, Leu, Val, or Trp. In conclusion, increasing dietary amino acid density improved FCR in broiler chicks, and the rate of improvement was dependent on the inclusion of an exogenous protease