Author Correction: Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

Reflective questioning to guide socially just global health reform: a narrative review and expert elicitation.

Recent research has highlighted the impacts of colonialism and racism in global health, yet few studies have presented concrete steps toward addressing the problems. We conducted a narrative review to identify published evidence that documented guiding frameworks for enhancing equity and inclusion in global health research and practice (GHRP). Based on this narrative review, we developed a questionnaire with a series of reflection questions related on commonly reported challenges related to diversity, inclusion, equity, and power imbalances. To reach consensus on a set of priority questions relevant to each theme, the questionnaire was sent to a sample of 18 global health experts virtually and two rounds of iterations were conducted. Results identified eight thematic areas and 19 reflective questions that can assist global health researchers and practitioners striving to implement socially just global health reforms. Key elements identified for improving GHRP include: (1) aiming to understand the historical context and power dynamics within the areas touched by the program; (2) promoting and mobilizing local stakeholders and leadership and ensuring measures for their participation in decision-making; (3) ensuring that knowledge products are co-produced and more equitably accessible; (4) establishing a more holistic feedback and accountability system to understand needed reforms based on local perspectives; and (5) applying systems thinking to addressing challenges and encouraging approaches that can be sustained long-term. GHRP professionals should reflect more deeply on how their goals align with those of their in-country collaborators. The consistent application of reflective processes has the potential to shift GHRP towards increased equity.

Risk factors for extended-spectrum beta-lactamase (ESBL)-producing E. coli carriage among children in a food animal-producing region of Ecuador: A repeated measures observational study.

BACKGROUND: The spread of antibiotic-resistant bacteria may be driven by human-animal-environment interactions, especially in regions with limited restrictions on antibiotic use, widespread food animal production, and free-roaming domestic animals. In this study, we aimed to identify risk factors related to commercial food animal production, small-scale or "backyard" food animal production, domestic animal ownership, and practices related to animal handling, waste disposal, and antibiotic use in Ecuadorian communities. METHODS AND FINDINGS: We conducted a repeated measures study from 2018 to 2021 in 7 semirural parishes of Quito, Ecuador to identify determinants of third-generation cephalosporin-resistant E. coli (3GCR-EC) and extended-spectrum beta-lactamase E. coli (ESBL-EC) in children. We collected 1,699 fecal samples from 600 children and 1,871 domestic animal fecal samples from 376 of the same households at up to 5 time points per household over the 3-year study period. We used multivariable log-binomial regression models to estimate relative risks (RR) of 3GCR-EC and ESBL-EC carriage, adjusting for child sex and age, caregiver education, household wealth, and recent child antibiotic use. Risk factors for 3GCR-EC included living within 5 km of more than 5 commercial food animal operations (RR: 1.26; 95% confidence interval (CI): 1.10, 1.45; p-value: 0.001), household pig ownership (RR: 1.23; 95% CI: 1.02, 1.48; p-value: 0.030) and child pet contact (RR: 1.23; 95% CI: 1.09, 1.39; p-value: 0.001). Risk factors for ESBL-EC were dog ownership (RR: 1.35; 95% CI: 1.00, 1.83; p-value: 0.053), child pet contact (RR: 1.54; 95% CI: 1.10, 2.16; p-value: 0.012), and placing animal feces on household land/crops (RR: 1.63; 95% CI: 1.09, 2.46; p-value: 0.019). The primary limitations of this study are the use of proxy and self-reported exposure measures and the use of a single beta-lactamase drug (ceftazidime with clavulanic acid) in combination disk diffusion tests for ESBL confirmation, potentially underestimating phenotypic ESBL production among cephalosporin-resistant E. coli isolates. To improve ESBL determination, it is recommended to use 2 combination disk diffusion tests (ceftazidime with clavulanic acid and cefotaxime with clavulanic acid) for ESBL confirmatory testing. Future studies should also characterize transmission pathways by assessing antibiotic resistance in commercial food animals and environmental reservoirs. CONCLUSIONS: In this study, we observed an increase in enteric colonization of antibiotic-resistant bacteria among children with exposures to domestic animals and their waste in the household environment and children living in areas with a higher density of commercial food animal production operations.

The role of plasmids in carbapenem resistant E. coli in Alameda County, California.

BACKGROUND: Antimicrobial resistant infections continue to be a leading global public health crisis. Mobile genetic elements, such as plasmids, have been shown to play a major role in the dissemination of antimicrobial resistance (AMR) genes. Despite its ongoing threat to human health, surveillance of AMR in the United States is often limited to phenotypic resistance. Genomic analyses are important to better understand the underlying resistance mechanisms, assess risk, and implement appropriate prevention strategies. This study aimed to investigate the extent of plasmid mediated antimicrobial resistance that can be inferred from short read sequences of carbapenem resistant E. coli (CR-Ec) in Alameda County, California. E. coli isolates from healthcare locations in Alameda County were sequenced using an Illumina MiSeq and assembled with Unicycler. Genomes were categorized according to predefined multilocus sequence typing (MLST) and core genome multilocus sequence typing (cgMLST) schemes. Resistance genes were identified and corresponding contigs were predicted to be plasmid-borne or chromosome-borne using two bioinformatic tools (MOB-suite and mlplasmids). RESULTS: Among 82 of CR-Ec identified between 2017 and 2019, twenty-five sequence types (STs) were detected. ST131 was the most prominent (n = 17) followed closely by ST405 (n = 12). blaCTX-M were the most common ESBL genes and just over half (18/30) of these genes were predicted to be plasmid-borne by both MOB-suite and mlplasmids. Three genetically related groups of E. coli isolates were identified with cgMLST. One of the groups contained an isolate with a chromosome-borne blaCTX-M-15 gene and an isolate with a plasmid-borne blaCTX-M-15 gene. CONCLUSIONS: This study provides insights into the dominant clonal groups driving carbapenem resistant E. coli infections in Alameda County, CA, USA clinical sites and highlights the relevance of whole-genome sequencing in routine local genomic surveillance. The finding of multi-drug resistant plasmids harboring high-risk resistance genes is of concern as it indicates a risk of dissemination to previously susceptible clonal groups, potentially complicating clinical and public health intervention.

Somewhere to go: assessing the impact of public restroom interventions on reports of open defecation in San Francisco, California from 2014 to 2020.

BACKGROUND: Open defecation due to a lack of access to sanitation facilities remains a public health issue in the United States. People experiencing homelessness face barriers to accessing sanitation facilities, and are often forced to practice open defecation on streets and sidewalks. Exposed feces may contain harmful pathogens posing a significant threat to public health, especially among unhoused persons living near open defecation sites. The City of San Francisco's Department of Public Works implemented the Pit Stop Program to provide the unhoused and the general public with improved access to sanitation with the goal of reducing fecal contamination on streets and sidewalks. The objective of this study was to assess the impact of these public restroom interventions on reports of exposed feces in San Francisco, California. METHODS: We evaluated the impact of various public restroom interventions implemented from January 1, 2014 to January 1, 2020 on reports of exposed feces, captured through a 311 municipal service. Publicly available 311 reports of exposed feces were spatially and temporally matched to 31 Pit Stop restroom interventions at 27 locations across 10 San Francisco neighborhoods. We conducted an interrupted time-series analysis to compare pre- versus post-intervention rates of feces reports near the restrooms. RESULTS: Feces reports declined by 12.47 reports per week after the installation of 13 Pit Stop restrooms (p-value = 0.0002). In the same restrooms, the rate of reports per week declined from the six-month pre-intervention period to the post-intervention period (slope change = -0.024 [95% CI = -0.033, -0.014]). In a subset of restrooms, where new installations were made (Mission and Golden Gate Park), and in another subset of restrooms where restroom attendants were provided (Mission, Castro/Upper Market, and Financial District/South Beach), feces reports also declined. CONCLUSIONS: Increased access to public toilets reduced feces reports in San Francisco, especially in neighborhoods with people experiencing homelessness. The addition of restroom attendants also appeared to have reduced feces reports in some neighborhoods with PEH. These interventions should be audited for implementation quality, observed utilization data, and user experience at the neighborhood level in order to tailor sanitation interventions to neighborhood-specific needs.

Antibiotic use by backyard food animal producers in Ecuador: a qualitative study.

BACKGROUND: Antibiotics are increasingly used throughout the world in food animal production for controlling and preventing disease and for promoting growth. But this trend also has the potential for promoting antibiotic resistance, which represents a threat to human, animal, and environmental health. The use of antibiotics and the potential effects of antibiotic dependence has often been associated with large-scale food animal production. But rural households also engage in small-scale production, often operating literally in backyards. While some small-scale producers use veterinary antibiotics, many do not. This paper examines knowledge, attitudes, beliefs, and agricultural practices (KAP) that represent an alternative to dependence on antibiotics. METHODS: Qualitative field research was based on four focus group discussions (FGDs) with non-indigenous backyard food animal producers in four communities near Quito, Ecuador and two FGDs with veterinarians. FGDs were supplemented by structured observations and key informant interviews. They were recorded with digital audio devices and transcriptions were analyzed independently by two researchers using a three-stage coding procedure. Open coding identifies underlying concepts, while axial coding develops categories and properties, and selective coding integrates the information in order to identify the key dimensions of the collective qualitative data. RESULTS: Backyard food animal producers in the Ecuadorian highlands generally do not use antibiotics while rearing small batches of animals and poultry for predominantly non-commercial household consumption. Instead, they rely on low cost traditional veterinary remedies. These practices are informed by their Andean history of agriculture and a belief system whereby physical activity is a holistic lifestyle through which people maintain their health by participating in the physical and spiritual environment. CONCLUSIONS: Backyard food animal producers in the Ecuadorian highlands implement complex strategies based on both economic calculations and sociocultural underpinnings that shape perceptions, attitudes, and practices. They use traditional veterinary remedies in lieu of antibiotics in most cases because limited production of food animals in small spaces contributes to a predictable household food supply, while at the same time conforming to traditional concepts of human and environmental health.

Effect of glecaprevir/pibrentasvir on weight-adjusted tacrolimus trough/dose ratios in heart and kidney transplant recipients.

OBJECTIVE: The pharmacokinetic implications of direct-acting antiviral (DAA) use on tacrolimus posttransplant are unknown. This study sought to investigate the effects of glecaprevir/pibrentasvir (G/P), a CYP3A4 substrate and inhibitor, on weight-adjusted tacrolimus (FK) trough/dose ratio (T/D) following heart or kidney transplantation. MATERIAL AND METHODS: This was a single-center, retrospective analysis of hepatitis C virus (HCV) viremic donors to HCV negative heart or kidney transplant recipients who received 12 weeks of G/P therapy. Weight-adjusted T/D was assessed while patients were at steady-state before, during, and after G/P treatment. Forty-one HCV negative recipients (three heart, 38 kidney) were evaluated. RESULTS: The weight-adjusted T/D significantly increased during G/P treatment (119.31, IQR 88-173.8) compared to before G/P treatment (67.4, IQR 53.4-115.9) (p < 0.01), but decreased after completion of treatment (90.1, IQR 52.9-122.7) (p < 0.01). There was no difference in weight-adjusted T/D before and after G/P treatment (p = 0.42). Four patients experienced acute rejection. CONCLUSION: Initiation of G/P in heart or kidney transplant recipients induces a reversible change in tacrolimus metabolism. A 33%-50% tacrolimus dose reduction may be considered at the time of G/P initiation. Regardless of tacrolimus dose adjustment, tacrolimus trough levels should be monitored 3 days after initiation of G/P. No clear relationship between HCV viremic organ transplantation and rejection risk was found. Larger studies are warranted to validate these findings.

Commercial insurance delays direct-acting antiviral treatment for hepatitis C kidney transplantation into uninfected recipients.

INTRODUCTION: The advent of direct-acting antivirals (DAAs) has created an avenue for transplantation of hepatitis C virus (HCV)-infected donors into uninfected recipients (D+/R-). The donor transmission of HCV is then countered by DAA administration during the post-operative period. However, initiation of DAA treatment is ultimately dictated by insurance companies. METHODS: A retrospective chart review of 52 D+/R- kidney recipients who underwent DAA treatment post-transplant was performed. Patients were grouped according to their prescription coverage plans, managed by either commercial or government pharmacy benefit managers (PBMs). RESULTS: Thirty-nine patients had government PBMs and 13 had commercial PBMs. Demographics were similar between the two groups. All patients developed HCV viremia, but cleared the virus after treatment with DAA. Patients with government PBMs were treated earlier compared to those with commercial PBMs (11 days vs 26 days, P = .01). Longer time to DAA initiation resulted in higher peak viral loads (ß = 0.39, R2  = .15, P = .01) and longer time to HCV viral load clearance (ß = 0.41, R2  = .17, P = .01). CONCLUSIONS: D+/R- transplantation offers patients an alternative strategy to increase access. However, treatment can be profoundly delayed by a third-party payer authorization process that may be subjecting patients to unnecessary risks and worsened outcomes.

COVID-19 infection in kidney transplant recipients at the epicenter of pandemics.

We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8%) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms; 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization.

Urgent Peritoneal Dialysis in Patients With COVID-19 and Acute Kidney Injury: A Single-Center Experience in a Time of Crisis in the United States.

At Montefiore Medical Center in The Bronx, NY, the first case of coronavirus disease 2019 (COVID-19) was admitted on March 11, 2020. At the height of the pandemic, there were 855 patients with COVID-19 admitted on April 13, 2020. Due to high demand for dialysis and shortages of staff and supplies, we started an urgent peritoneal dialysis (PD) program. From April 1 to April 22, a total of 30 patients were started on PD. Of those 30 patients, 14 died during their hospitalization, 8 were discharged, and 8 were still hospitalized as of May 14, 2020. Although the PD program was successful in its ability to provide much-needed kidney replacement therapy when hemodialysis was not available, challenges to delivering adequate PD dosage included difficulties providing nurse training and availability of supplies. Providing adequate clearance and ultrafiltration for patients in intensive care units was especially difficult due to the high prevalence of a hypercatabolic state, volume overload, and prone positioning. PD was more easily performed in non-critically ill patients outside the intensive care unit. Despite these challenges, we demonstrate that urgent PD is a feasible alternative to hemodialysis in situations with critical resource shortages.

Transplantation of viral-positive hepatitis C-positive kidneys into uninfected recipients offers an opportunity to increase organ access.

The advent of direct-acting antivirals (DAAs) has provided the impetus to transplant kidneys from hepatitis C virus-positive donors into uninfected recipients (D+/R-). Thirty D+/R- patients received DAA treatment. Sustained virologic response (SVR12) was defined as an undetectable viral load in 12 weeks after treatment. An age-matched cohort of uninfected donor and recipient pairs (D-/R-) transplanted during same time period was used for comparison. The median day of viral detection was postoperative day (POD) 2. The detection of viremia in D+/R- patients was 100%. The initial median viral load was 531 copies/µL (range: 10-1 × 108 copies/µL) with a median peak viral load of 3.4 × 105 copies/µL (range: 804-1.0 × 108 copies/µL). DAAs were initiated on median POD 9 (range: 5-41 days). All 30 patients had confirmed SVR12. During a median follow-up of 10 months, patient and graft survival was 100%, and acute rejection was 6.6% with no major adverse events related to DAA treatment. Delayed graft function was significantly decreased in D+/R- patients as compared to the age-matched cohort (27% vs 60%; P = .01). D+/R- transplantation offers patients an alternative strategy to increase access.

Monthly Extended-Release Risperidone (RBP-7000) in the Treatment of Schizophrenia: Results From the Phase 3 Program.

PURPOSE/BACKGROUND: The Phase 3 program for RBP-7000, a once-monthly subcutaneous (SC) extended-release risperidone formulation approved for treatment of schizophrenia, consisted of a double-blind placebo-controlled trial (previously reported) and a 52-week open-label study of monthly RBP-7000 120 mg. The primary objective of the open-label study was to evaluate the long-term safety and tolerability of RBP-7000 in adults with schizophrenia. A secondary objective was to assess long-term maintenance of effectiveness. METHODS/PROCEDURES: The 52-week Phase 3 open-label study (NCT02203838) enrolled 92 rollover participants from the double-blind trial (NCT02109562) and 408 stable (Positive and Negative Syndrome Scale [PANSS] total score, ≤70) de novo participants. Participants received up to 13 monthly SC injections of RBP-7000 120 mg. Safety assessments included treatment-emergent adverse events, injection-site assessments, vital signs, laboratory and ECG parameters, extrapyramidal symptoms, and suicidality. Clinical outcomes included the PANSS and Clinical Global Impression-Severity. FINDINGS/RESULTS: Overall, 367 participants (73.4%) reported 1 or more treatment-emergent adverse event; the most common were injection-site pain (13.0%) and weight increase (12.8%). Most participants (>80%) experienced no injection-site reactions. No clinically meaningful changes were observed in laboratory or electrocardiogram values, vital signs, extrapyramidal symptoms, or suicidality. Over 12 months of exposure, mean PANSS scores continued to improve in rollover participants and remained stable among de novo participants. Mean Clinical Global Impression-Severity scores remained stable among all participants. IMPLICATIONS/CONCLUSIONS: Except for anticipated injection-site reactions, RBP-7000 demonstrated a favorable safety and tolerability profile similar to oral risperidone. Notably, PANSS scores continued to improve for participants from the pivotal study and remained stable for de novo participants.

Improving pancreas graft utilization through importation.

BACKGROUND: We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation. METHODS: This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost-effectiveness of this strategy. RESULTS: Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney-pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs. CONCLUSIONS: Imported pancreas grafts may be a cost-effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times.

Detection of Zoonotic Enteropathogens in Children and Domestic Animals in a Semirural Community in Ecuador.

UNLABELLED: Animals are important reservoirs of zoonotic enteropathogens, and transmission to humans occurs more frequently in low- and middle-income countries (LMICs), where small-scale livestock production is common. In this study, we investigated the presence of zoonotic enteropathogens in stool samples from 64 asymptomatic children and 203 domestic animals of 62 households in a semirural community in Ecuador between June and August 2014. Multilocus sequence typing (MLST) was used to assess zoonotic transmission of Campylobacter jejuni and atypical enteropathogenic Escherichia coli (aEPEC), which were the most prevalent bacterial pathogens in children and domestic animals (30.7% and 10.5%, respectively). Four sequence types (STs) of C. jejuni and four STs of aEPEC were identical between children and domestic animals. The apparent sources of human infection were chickens, dogs, guinea pigs, and rabbits for C. jejuni and pigs, dogs, and chickens for aEPEC. Other pathogens detected in children and domestic animals were Giardia lamblia (13.1%), Cryptosporidium parvum (1.1%), and Shiga toxin-producing E. coli (STEC) (2.6%). Salmonella enterica was detected in 5 dogs and Yersinia enterocolitica was identified in 1 pig. Even though we identified 7 enteric pathogens in children, we encountered evidence of active transmission between domestic animals and humans only for C. jejuni and aEPEC. We also found evidence that C. jejuni strains from chickens were more likely to be transmitted to humans than those coming from other domestic animals. Our findings demonstrate the complex nature of enteropathogen transmission between domestic animals and humans and stress the need for further studies. IMPORTANCE: We found evidence that Campylobacter jejuni, Giardia, and aEPEC organisms were the most common zoonotic enteropathogens in children and domestic animals in a region close to Quito, the capital of Ecuador. Genetic analysis of the isolates suggests transmission of some genotypes of C. jejuni and aEPEC from domestic animals to humans in this region. We also found that the genotypes associated with C. jejuni from chickens were present more often in children than were those from other domestic animals. The potential environmental factors associated with transmission of these pathogens to humans then are discussed.

Challenges and opportunities associated with neglected tropical disease and water, sanitation and hygiene intersectoral integration programs.

BACKGROUND: Recent research has suggested that water, sanitation, and hygiene (WASH) interventions, in addition to mass drug administration (MDA), are necessary for controlling and eliminating many neglected tropical diseases (NTDs). OBJECTIVES: This study investigated the integration of NTD and WASH programming in order to identify barriers to widespread integration and make recommendations about ideal conditions and best practices critical to future integrated programs. METHODS: Twenty-four in-depth, semi-structured interviews were conducted with key stakeholders in the global NTD and WASH sectors to identify barriers and ideal conditions in programmatic integration. RESULTS: The most frequently mentioned barriers to WASH and NTD integration included: 1) differing programmatic objectives in the two sectors, including different indicators and metrics; 2) a disproportionate focus on mass drug administration; 3) differences in the scale of funding; 4) siloed funding; and 5) a lack of coordination and information sharing between the two sectors. Participants also conveyed that a more holistic approach was needed if future integration efforts are to be scaled-up. The most commonly mentioned requisite conditions included: 1) education and advocacy; 2) development of joint indicators; 3) increased involvement at the ministerial level; 4) integrated strategy development; 5) creating task forces or committed partnerships; and 6) improved donor support. CONCLUSIONS: Public health practitioners planning to integrate NTD and WASH programs can apply these results to create conditions for more effective programs and mitigate barriers to success. Donor agencies should consider funding more integration efforts to further test the proof of principle, and additional support from national and local governments is recommended if integration efforts are to succeed. Intersectoral efforts that include the development of shared indicators and objectives are needed to foster conditions conducive to expanding effective integration programs.

Analysis of behavioral change techniques in community-led total sanitation programs.

The lack of sanitation facilitates the spread of diarrheal diseases-a leading cause of child deaths worldwide. As of 2012, an estimated 1 billion people still practiced open defecation (OD). To address this issue, one behavioral change approach used is community-led total sanitation (CLTS). It is now applied in an estimated 66 countries worldwide, and many countries have adopted this approach as their main strategy for scaling up rural sanitation coverage. While it appears that many of the activities used in CLTS-that target community-level changes in sanitation behaviors instead of household-level changes-have evolved out of existing behavior change frameworks and techniques, it is less clear how these activities are adapted by different organizations and applied in different country contexts. The aims of this study are to (i) show which behavior change frameworks and techniques are the most common in CLTS interventions; (ii) describe how activities are implemented in CLTS interventions by region and context; and (3) determine which activities program implementers considered the most valuable in achieving open defecation free (ODF) status and sustaining it. The results indicate that a wide range of activities are conducted across the different programs and often go beyond standard CLTS activities. CLTS practitioners ranked follow-up and monitoring activities as the most important activities for achieving an ODF community, yet only 1 of 10 organizations conducted monitoring and follow-up throughout their project. Empirical studies are needed to determine which specific behavioral change activities are most effective at ending OD and sustaining it.

"Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology.

As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex vivo techniques such as hypothermic, normothermic, and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury. Moreover, other preservation techniques such as oxygen persufflation are explored as they may also have a role in improving function of "marginal" liver allografts. Currently, marginal livers are frequently discarded or can relegate the patient to early allograft dysfunction and primary non-function. Bench to bedside advances are rapidly emerging and hold promise for expanding liver transplantation access and improving outcomes.

Trends in access to water supply and sanitation in 31 major sub-Saharan African cities: an analysis of DHS data from 2000 to 2012.

BACKGROUND: By 2050, sub-Saharan Africa's (SSA) urban population is expected to grow from 414 million to over 1.2 billion. This growth will likely increase challenges to municipalities attempting to provide access to water supply and sanitation (WS&S). This study aims to characterize trends in access to WS&S in SSA cities and identify factors affecting those trends. METHODS: DHS data collected between 2000 and 2012 were used for this analysis of thirty-one cities in SSA. Four categories of household access to WS&S were studied using data from demographic and health surveys--these included: 1) household access to an improved water supply, 2) household's time spent collecting water, 3) household access to improved sanitation, and 4) households reporting to engage in open defecation. An exploratory analysis of these measures was then conducted to assess the relationship of access to several independent variables. RESULTS: Among the 31 cities, there was wide variability in coverage levels and trends in coverage with respect to the four categories of access. The majority of cities were found to be increasing access in the categories of improved water supply and improved sanitation (65% and 83% of cities, respectively), while fewer were making progress in reducing the amount of time spent collecting water and reducing open defecation (50% and 38% of cities, respectively). Additionally, the prevalence of open defecation in study cities was found to be, on average, increasing. CONCLUSIONS: Based on DHS data, cities appeared to be making the most progress in gaining access to WS&S along metrics which reflect specified targets of the Millennium Development Goals. Nearly half of the cities, however, did not make progress in reducing open defecation or the time spent collecting water. This may reflect that the MDGs have led to a focus on "improved" services while other measures, potentially more relevant to the extreme poor, are being neglected. This study highlights the need to better characterize access, beyond definitions of improved and unimproved, as well as the need to target resources to cities where changes in WS&S access have stalled, or in some cases regressed.