Search

Transect surveys are widely used to quantify mismanaged plastic waste discarded to the environment. However, very few studies have quantified inter-observer reliability in environmental waste surveys. The aim of this study was to assess inter-observer reliability for a set of environmental waste indicators derived from transect surveys in slum areas of two sub-Saharan African cities. Pairs of observers independently recorded counts of scattered waste items, large waste piles, and burnt waste along 64 environmental transects in Kisumu, Kenya, and Greater Accra, Ghana. Concordance correlation coefficients were used to measure inter-observer reliability for derived indicators measuring mismanaged waste density, waste composition, waste origins of policy concern, and waste disposal practices. Evidence across all observers consistently showed that single-use disposable diapers, discarded Personal Protective Equipment, and bagged or bottled water are locally important constituents of mismanaged waste in both cities that should be addressed through urban waste management strategies. In both cities, there was generally excellent inter-observer reliability for density of burnt waste and density of large waste piles (concordance correlation coefficient > 0.9 for all but one observer pair), but weak to moderate inter-observer reliability for scattered waste density and densities of specific waste items such as disposable nappies and discarded Personal Protective Equipment. Our study shows that beach litter survey protocols can be adapted for use in slums. However, to generate robust estimates of scattered waste, its composition, and waste origins of policy concern in slums, assessment of inter-observer reliability should be incorporated into field team training.

Scalable syntheses of the northern macrobicyclic thiolincosamine fragments of two structurally complex antibiotic candidates, BT-33 and cresomycin, are presented. A key transformation in each route is the highly diastereoselective addition of a putative allenylzinc nucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted Barbier-type propargylation protocol that is detailed herein. These transformations proceed with dynamic kinetic resolution and use just 1.2 equiv of each respective propargyl bromide precursor.

•New synthetic lincosamides, iboxamycin and cresomycin, display potent in vitroactivity against ocular methicillin-resistant Staphylococcus aureus(MRSA) isolates.•Both drugs are active against widespread MRSA clonal complexes CC8 and CC5.•The in vitropotencies of iboxamycin and cresomycin are not impacted by multidrug-resistance phenotypes or by the presence of ermgenes when compared with clindamycin.

The article focuses on the pervasive impact of misinformation and disinformation, highlighting its effects on public perception, health decisions, political beliefs, and societal divisions. Topics include the misleading nature of crime perceptions versus reality, the deadly consequences of COVID-19 misinformation on vaccination rates and mortality.

The bacterial ribosome is an essential drug target as many clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent resistance mechanisms to PTC-acting drugs in Gram-positive bacteria is C8-methylation of the universally conserved A2503 nucleobase by Cfr methylase in 23S ribosomal RNA. Despite its clinical importance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. Here, we report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-transfer RNAs. These structures reveal an allosteric rearrangement of nucleotide A2062 upon Cfr-mediated methylation of A2503 that likely contributes to the reduced potency of some PTC inhibitors. Additionally, we provide the structural bases behind two distinct mechanisms of engaging the Cfr-methylated ribosome by the antibiotics iboxamycin and tylosin.

Three dominant characteristics and underlying dynamics of the seasonal cycle in Baffin Bay are discussed. The study is based on a regional, high‐resolution coupled sea ice‐ocean numerical model that complements our understanding drawn from observations. Subject to forcing from the atmosphere, sea ice, Greenland, and other ocean basins, the ocean circulation exhibits complex seasonal variations that influence Arctic freshwater storage and export. The basin‐scale barotropic circulation is generally stronger (weaker) in summer (winter). The interior recirculation (∼2 Sv) is primarily driven by oscillating along‐topography surface stress. The volume transport along the Baffin Island coast is also influenced by Arctic inflows (∼0.6 Sv) via Smith Sound and Lancaster Sound with maximum (minimum) in June‐August (October‐December). In addition to the barotropic variation, the Baffin Island Current also has changing vertical structure with the upper‐ocean baroclinicity weakened in winter‐spring. It is due to a cross‐shelf circulation associated with spatially variable ice‐ocean stresses that flattens isopycnals. Greenland runoff and sea ice processes dominate buoyancy forcing to Baffin Bay. Opposite to the runoff that freshens the west Greenland shelf, stronger salinification by ice formation compared to freshening by ice melt enables a net densification in the interior of Baffin Bay. Net sea ice formation in the past 30 years contributes to ∼25% of sea ice export via Davis Strait. The seasonal variability in baroclinicity and water mass transformation changes in recent decades based on the simulation. Baffin Bay ocean circulation is important for Arctic freshwater exports that may influence subpolar deep convection. However, we have little knowledge about how it works in winter due to limited observations. This study investigates three dominant aspects of the seasonal cycle in Baffin Bay ocean circulation and hydrography with a high‐resolution ice‐ocean coupled model. The basin‐scale barotropic circulation (depth‐integrated transport) is stronger in summer and weaker in winter, mainly driven by along‐topography surface stress and Arctic inflows. The baroclinicity (vertical velocity shear) of the Baffin Island Current is weakened in winter associated with spatially uneven ice‐ocean stresses. Net sea ice formation in Baffin Bay in the past 30 years makes Baffin Bay water densified and increases the sea ice export through Davis Strait. Changes of seasonality in Baffin Bay in the past 30 years are also discussed using model results. Basin‐scale barotropic circulation varies seasonally and is mainly forced by along‐topography surface stressBaffin Island Current is less surface intensified in ice seasons due to ice‐ocean stress curl induced cross‐shelf circulationNet sea ice formation makes Baffin Bay water densified and increases the sea ice export through Davis Strait Basin‐scale barotropic circulation varies seasonally and is mainly forced by along‐topography surface stress Baffin Island Current is less surface intensified in ice seasons due to ice‐ocean stress curl induced cross‐shelf circulation Net sea ice formation makes Baffin Bay water densified and increases the sea ice export through Davis Strait

As the Arctic warms at an increased rate compared to the rest of the globe, freshwater runoff has been shown to be increasing into the Arctic Ocean. The effects of this contemporary increase in riverine freshwater into the Arctic Ocean are estimated from ocean model simulations, using two runoff data sets. One runoff data set is based on older climatological data, which has no inter‐annual variability after 2007 and as such does not represent the observed increases in river runoff into the Arctic. The other data set comes from a hydrological model developed for the Arctic drainage basin, which includes contemporary changes in the climate. At the Pan‐Arctic scale this new data set represents an approximately 11% increase in runoff, compared with the older climatological data. Comparing two ocean model runs forced with the different runoff data sets, overall changes in different freshwater markers across the basin were found to be between 5% and 10%, depending on the regions. The strongest increases were seen from the Siberian rivers, which in turn caused the strongest freshening in the Eastern Arctic. As the surface waters of the Arctic Ocean are sensitive to runoff, incorporating hydrological model data can help to better understand current changes and potential future impacts from increased runoff with climate change. Climate change increases freshwater supply to the Arctic. This study looks at understanding the impacts of this increased riverine water into the Arctic Ocean using a state of the art regional ocean model. Two runoff forcing data sets are used, one data set which only extends to 2007 and thus does not include the recently observed runoff increases due to climate change, and a newer data set which extends up to present day and as such represents contemporary increases in the river runoff into the Arctic. Comparing two simulations forced by the two runoff datasets highlights the effects of river runoff changes on the Arctic Ocean. We find the Arctic surface waters freshen by 5%–10% over 2007–2018, depending on the metric and region considered. Much of this increased freshwater found is driven by the major Siberian rivers. This primarily affects the Eastern Arctic. Our work shows that recently observed increases in Arctic river runoff are likely impacting surface Arctic waters as well as waters transported to lower latitudes. Pan‐Arctic river runoff increased by 11% over 2002–2019 according to hydrological model outputIn ocean model simulations this dataset gave a subsequent surface freshening of 5%–10%, as compared with classical runoff climatologySiberian rivers dominate runoff and are the main source of differences, enhancing export through Fram and Davis Straits, as observed Pan‐Arctic river runoff increased by 11% over 2002–2019 according to hydrological model output In ocean model simulations this dataset gave a subsequent surface freshening of 5%–10%, as compared with classical runoff climatology Siberian rivers dominate runoff and are the main source of differences, enhancing export through Fram and Davis Straits, as observed

The Internal Revenue Service (IRS) and Department of Treasury, together with the White House, recently released four pieces of guidance with the stated purpose of easing certain burdens on providing [...]

illus por, Supplement: Celebrating 100 years of naval aviation

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.amjsurg.2010.07.026 Byline: Craig O. Daniel (a), T.A. West (a), Phyllis S. Craig-Blanco (a), John G. Myers (b), Ronald M. Stewart (b) Keywords: Outcomes; Rural; Trauma systems; Injury Abstract: Level III trauma centers are an effective component of a healthy trauma system. This study examined the effectiveness over time of a Level III trauma center in a predominately rural region. Author Affiliation: (a) Medical Center Hospital, 500 W. 4th, Odessa, TX 79761, USA (b) University of Texas Health Science Center at San Antonio, San Antonio, TX Article History: Received 10 March 2010; Revised 2 July 2010 Article Note: (footnote) No potential conflicts of interest relevant to this article were reported.

OBJECTIVE--To characterize the hormonal milieu and adipose gene expression in response to catch-up growth (CUG), a growth pattern associated with obesity and diabetes risk, in a mouse model of low birth weight (LBW). RESEARCH DESIGN AND METHODS--ICR mice were food restricted by 50% from gestational days 12.5-18.5, reducing offspring birth weight by 25%. During the suckling period, dams were either fed ad libitum, permitting CUG in offspring, or food restricted, preventing CUG. Offspring were killed at age 3 weeks, and gonadal fat was removed for RNA extraction, array analysis, RT-PCR, and evaluation of cell size and number. Serum insulin, thyroxine (T4), corticosterone, and adipokines were measured. RESULTS--At age 3 weeks, LBW mice with CUG (designated U-C) had body weight comparable with controls (designated C-C); weight was reduced by 49% in LBW mice without CUG (designated U-U). Adiposity was altered by postnatal nutrition, with gonadal fat increased by 50% in U-C and decreased by 58% in U-U mice (P < 0.05 vs. C-C mice). Adipose expression of the lipogenic genes Fasn, AccI, Lpin1, and Srebf1 was significantly increased in U-C compared with both C-C and U-U mice (P < 0.05). Mitochondrial DNA copy number was reduced by >50% in U-C versus U-U mice (P = 0.014). Although cell numbers did not differ, mean adipocyte diameter was increased in U-C and reduced in U-U mice (P < 0.01). CONCLUSIONS--CUG results in increased adipose tissue lipogenic gene expression and adipocyte diameter but not increased cellularity, suggesting that catch-up fat is primarily associated with lipogenesis rather than adipogenesis in this murine model., Low-birth weight (LBW) infants are at increased risk for hypertension, type 2 diabetes, and metabolic syndrome (1). Mechanisms remain ill defined but may involve epigenetic regulation of development and gene [...]

Media summary:Large prospective multicenter study showed that prehospital tourniquets for major extremity trauma were associated with a threefold decreased incidence of arrival in shock without increased limb complications. #stopthebleed @BeccaSchroll @TraumaTulane.

The article presents advice for employees in business organizations suffering from stress, particularly recommending business learning as a coping mechanism. According to the article, employees experience an alleviation of negative emotions and stress when actively learning in the workplace. The article also recommends strategies for work learning including working with others, and using learning as a break from work.

This study investigates the biogeochemical drivers of aragonite saturation state (ΩAr) in Baffin Bay, with a focus on the relatively undersampled west Greenland shelf. Our findings reveal two main depth‐dependant processes controlling the spatial distribution of ΩArin Baffin Bay; within the upper 200 m, lower ΩArcoincides with increasing fractions of Arctic‐outflow waters, while below 200 m organic matter respiration decreases ΩAr. A temporal analysis comparing historical measurements from 1997 and 2004 with our 2019 data set reveals a significant decrease in the ΩArof Arctic‐outflow waters, coinciding with reduced total alkalinity (TA). However, no discernible anthropogenic ocean acidification signal is identified. Significant Arctic water fractions (20%–40%) are found to be present on the west Greenland shelf, associated with reduced TA and ΩAr. A numerical modeling simulation incorporating a passive tracer demonstrates that periodic changes in wind direction lead to a switch from onshore to offshore Ekman transport along the Baffin Island current, transporting Arctic waters toward the west Greenland shelf. This challenges the conventional understanding of Baffin Bay's circulation and underscores the need for further research on the region's physical oceanography. Based on salinity‐TA relationships, surface waters on the west Greenland shelf have a significantly lower meteoric TA end‐member compared to waters of the Baffin Island Current in western Baffin Bay. The low eastern TA freshwater end‐member agrees well with recent glacial meltwater TA measurements, suggesting that glacial meltwater is the main freshwater source to surface waters on the west Greenland shelf. Baffin Bay, with its complex interplay of Atlantic and Arctic water masses, is particularly susceptible to ongoing ocean acidification, mainly due to the presence of relatively fresh and low‐alkalinity Arctic waters. To date measurements of the inorganic carbon system in Baffin Bay have primarily been captured at key entrance and exit gateways, and on the Canadian side of the bay, leaving the west Greenland shelf relatively undersampled. This study provides a bay‐wide perspective of the main factors influencing aragonite saturation state (ΩAr; an indicator of ocean acidification impacts on marine calcifying organisms) across Baffin Bay, including the west Greenland shelf. We found that within the upper 200 m, low ΩArcoincides with increased presence of Arctic waters, while below 200 m the breakdown of organic matter decreases ΩAr. Historical data from 1997 and 2004 compared to our 2019 measurements show a significant drop in ΩArof Arctic waters, but no clear signal of anthropogenic ocean acidification was observed. Surprisingly, the west Greenland shelf has significant fractions (20%–40%) of Arctic water. A numerical modeling simulation suggests that periodic changes in wind direction can transport Arctic waters from across Baffin Bay, challenging our traditional understanding of the bay's circulation. Increased fractions of Arctic waters decrease aragonite saturation state (ΩAr) in the upper 200 m, while respiration does so below 200 mDecreased ΩArof Arctic waters over the last two decades is associated with decreased alkalinity, not additional CO2Significant fractions of Arctic‐outflow waters on the west Greenland shelf challenges current knowledge of circulation in Baffin Bay Increased fractions of Arctic waters decrease aragonite saturation state (ΩAr) in the upper 200 m, while respiration does so below 200 m Decreased ΩArof Arctic waters over the last two decades is associated with decreased alkalinity, not additional CO2 Significant fractions of Arctic‐outflow waters on the west Greenland shelf challenges current knowledge of circulation in Baffin Bay

After a career spent pondering the connections between subjective and objective truth, feeling and fact, and intuition and reality, I'm predisposed to welcoming unbidden hunches. I once took an instant [...]

Objective: This study investigated the progression from conduct disorder to antisocial personality disorder among individuals treated for adolescent substance abuse. This issue is important because of the poor outcomes observed among individuals with antisocial pathology after treatment for alcohol and drug problems. The utility of factors assessed at the time of treatment in predicting progression to adult antisocial personality disorder was evaluated in the context of developmental models of antisocial behavior. Method: This was a prospective longitudinal study of 137 substance-abusing adolescents (53 female and 84 male), whose average age was 15.9 years and who met the DSM-III-R criteria for conduct disorder. Consecutively admitted patients were recruited from two adolescent inpatient alcohol and drug treatment facilities. Participants were interviewed again 4 years after treatment. Results: Four years after treatment, 61% of the study group met the DSM-III-R criteria for antisocial personality disorder. Results of a logistic regression analysis indicated that onset of deviant behavior at or before age 10, a greater diversity of deviant behavior, and more extensive pretreatment drug use best predicted progression to antisocial personality disorder. At 4-year follow-up, the subjects with an antisocial personality disorder diagnosis exhibited more involvement with alcohol and drugs and poorer functioning across important life domains than the subjects without antisocial personality disorder. Conclusions: This study found a high rate of progression to antisocial personality disorder among substance-abusing adolescents and identified factors predictive of this progression. Careful assessment of conduct disorder history at the time of treatment may be valuable for treatment planning and intervention.

Objective: The authors investigated the theoretical and clinical role of depression among cocaine abusers in treatment. Method: Eighty-nine cocaine-abusing patients underwent 2 weeks of substance abuse treatment. Posttreatment major depressive disorder, depressive symptoms before and after substance abuse treatment, and alcohol diagnoses were assessed and their relation to pretreatment substance use, cravings in high-risk situations, and 3-month follow-up status was examined. Results: High rates of major depressive disorder were found but were unrelated to pretreatment substance use. The decrease in depressive symptoms during treatment was independent of major depressive disorder or alcohol diagnoses and predicted treatment attrition. Higher levels of depressive symptoms during treatment were associated with greater urge to use cocaine, alcohol, and other drugs in high-risk situations. Concurrent major depressive disorder and depressive symptoms did not predict cocaine use at follow-up. However, patients who had an alcohol relapse episode experienced more depressive symptoms during treatment than did those who abstained. Conclusions: The results highlight the relationship of depression to alcohol use among cocaine abusers and suggest a need for further studies of the association between depression and substance use disorders.

Background: Growth factor receptor-signaling pathways are potentially important targets for anticancer therapy. The interaction of anticancer agents with specific molecular targets can be identified by correlating target expression patterns with cytotoxicity patterns. We sought to identify new agents that target and inhibit the activity of the epidermal growth factor (EGF) receptor and of c-erbB2 (also called HER2 or neu), by correlating EGF receptor, transforming growth factor (TGF)-[Alpha] (a ligand for EGF receptor), and c-erbB2 messenger RNA (mRNA) expression levels with the results of cytotoxicity assays of the 49 000 compounds in the National Cancer Institute (NCI) drug screen database. Methods: The levels of mRNAs were measured and used to generate a molecular target database for the 60 cell lines of the NCI anticancer drug screen. The computer analysis program, COMPARE, was used to search for cytotoxicity patterns in the NCI drug screen database that were highly correlated with EGF receptor, TGF-[Alpha], or c-erbB2 mRNA expression patterns. The putative EGF receptor-inhibiting compounds were tested for effects on basal tyrosine phosphorylation, in vitro EGF receptor tyrosine kinase activity, and EGF-dependent growth. Putative ErbB2-inhibiting compounds were tested for effects on antibody-induced ErbB2 tyrosine kinase activity. Results: EGF receptor mRNA and TGF-[Alpha] mRNA levels were highest in cell lines derived from renal cancers, and c-erbB2 mRNA levels were highest in cells derived from breast, ovarian, and colon cancers. Twenty-five compounds with high correlation coefficients (for cytotoxicity and levels of the measured mRNAs) were tested as inhibitors of the EGF receptor or c-erbB2 signaling pathways; 14 compounds were identified as inhibitors of these pathways. The most potent compound, B4, inhibited autophosphorylation (which occurs following activation) of ErbB2 by 50% in whole cells at 7.7 [Micro] M. Conclusions: Novel EGF receptor or c-erbB2 pathway inhibitors can be identified in the NCI drug screen by correlation of cytotoxicity patterns with EGF receptor or c-erbB2 mRNA expression levels. [J Natl Cancer Inst 1997;89:1505-15]

Scientists zero in on who is happy and why. Their findings may help more people find happiness in the years ahead. For millions of people, finding the right partner, achieving [...]

The dearth of new medicines effective against antibiotic-resistant bacteria presents a growing global public health concern1. For more than five decades, the search for new antibiotics has relied heavily on the chemical modification of natural products (semisynthesis), a method ill-equipped to combat rapidly evolving resistance threats. Semisynthetic modifications are typically of limited scope within polyfunctional antibiotics, usually increase molecular weight, and seldom permit modifications of the underlying scaffold. When properly designed, fully synthetic routes can easily address these shortcomings2. Here we report the structure-guided design and component-based synthesis of a rigid oxepanoproline scaffold which, when linked to the aminooctose residue of clindamycin, produces an antibiotic of exceptional potency and spectrum of activity, which we name iboxamycin. Iboxamycin is effective against ESKAPE pathogens including strains expressing Erm and Cfr ribosomal RNA methyltransferase enzymes, products of genes that confer resistance to all clinically relevant antibiotics targeting the large ribosomal subunit, namely macrolides, lincosamides, phenicols, oxazolidinones, pleuromutilins and streptogramins. X-ray crystallographic studies of iboxamycin in complex with the native bacterial ribosome, as well as with the Erm-methylated ribosome, uncover the structural basis for this enhanced activity, including a displacement of the m26A2058nucleotide upon antibiotic binding. Iboxamycin is orally bioavailable, safe and effective in treating both Gram-positive and Gram-negative bacterial infections in mice, attesting to the capacity for chemical synthesis to provide new antibiotics in an era of increasing resistance.