bluuebunny/crossref_metadata_2025 huggingface dataset:
Interfacility Spread of OXA-23–Producing Carbapenem-Resistant Acinetobacter—Connecticut, 2018–2019
Authors: Jones Sydney , Maloney Meghan , Paranandi Anu , Pepe Dana , Nazarian Elizabeth , Morris Shannon , Christine Wagner , Bodnar Janine , Cummings Kailee , Leung Vivian
Published: November 2020

Background: Carbapenem-resistant Acinetobacter baumannii (CRAB), a multidrug-resistant gram-negative bacterium, can cause difficult-to-treat infections with mortality in approximately half of CRAB cases. CRAB can spread among healthcare facilities after transfer of an infected or colonized patient. Strategies to limit CRAB spread include adherence to contact precautions, environmental cleaning with bleach, and screening to identify colonized patients. During July–September 2018, the Connecticut Department of Public Health (DPH) worked with an acute-care hospital (hospital A) to contain an outbreak of OXA-23–producing CRAB (OXA-23 is an enzyme that confers resistance to carbapenems). During November 2018–March 2019, statewide CRAB surveillance identified additional cases of related OXA-23–producing CRAB at other healthcare facilities. DPH, Connecticut State Public Health Laboratory (SPHL), and the Antibiotic Resistance Laboratory Network (ARLN) investigated to prevent additional cases. Methods: Since January 2017, CRAB isolates have been routinely sent to SPHL and ARLN for carbapenemase gene detection and whole-genome sequencing (WGS) to determine isolate relatedness. During November 2018–March 2019, DPH collected patient healthcare history for patients with CRAB isolates to identify outbreaks and provide assistance in infection control and prevention to healthcare facilities reporting CRAB cases. Beginning May 2019, DPH and ARLN offered facilities screening to identify patients colonized with OXA-23–producing CRAB. Results: Of 10 OXA-23–producing CRAB isolates reported to DPH during November 2018–March 2019, 3 were closely related to the 9 isolates from hospital A’s outbreak by WGS (single-nucleotide polymorphism difference range, 1–16). One isolate was from a patient who had been admitted to hospital A during July 2018. All 3 patients with CRAB isolates shared a history of residence at long-term–care facility A (LTCF A). Two patients received a CRAB infection diagnosis upon admission to hospital B after transfer from LTCF A. Both LTCF A and hospital B performed environmental cleaning with bleach and placed CRAB-identified patients on contact precautions. LTCF A declined screening patients for CRAB, whereas hospitals B and C, which receive frequent transfers from LTCF A, screened all patients on admission from LTCF A. During May–September 2019, among 6 patients screened, 1 was colonized with OXA-23–producing CRAB and was placed on contact precautions. Conclusions: Transfer of patients who are infected or colonized with CRAB among hospitals and LTCFs can facilitate the regional spread of CRAB. Strategies for containing the spread of carbapenemase-producing organisms include adherence to contact precautions, colonization screening, interfacility communication, and collaboration with public health.

Funding: None

Disclosures: None
Like a Bat Out of…. the Hospital? Development of a Bat Capture and Testing Protocol Prompted by Two Nosocomial Encounters
Authors: Kessler Michael , Shirley Daniel , Anderson Laura , Safdar Nasia
Published: November 2020

Background: In the state of Wisconsin, 3%–4% of bats submitted for rabies testing are positive. Inpatient bat encounters at 2 affiliated healthcare facilities at nearly the same time were brought to the attention of the infection prevention and control (IPC) team. The first bat was captured in a patient room and was submitted for testing. Postexposure prophylaxis (PEP) was initiated for 1 patient before the bat testing results came back negative. The second bat was found in a transplant unit hallway and was released before we could request testing. We observed significant variations in responses, including decision to administer PEP and submission of bats for rabies testing. The IPC team developed a protocol to minimize unnecessary PEP, to prevent nosocomial rabies infection from bat exposure, and to limit associated panic. Methods: A systematic literature review of multiple databases was performed. A search of nonscientific articles using Google was also performed to assess unpublished inpatient bat encounters. A workgroup was established including IPC staff, physicians, and facilities management. The county animal services department and the state public health department veterinarian were consulted to aid in development of a protocol. Results: Literature review yielded a single report of a bat discovered in a neonatal intensive care unit (NICU). A lack of protocol resulted in PEP administration to 7 neonates without observed exposure after the bat was released instead of being submitted for testing. Of the first 100 articles retrieved via Google search of “bat in hospital,” 9 pertained to nosocomial discovery of bats in 5 different states over the past 7 years. Encounters included infestations requiring unit shutdowns and PEP administration. One tertiary-care referral center reported 10 encounters per year but did not elaborate on associated procedures. The county animal services staff assisted in training maintenance and engineering services (MES) personnel on how to secure bats for testing and helped develop a “bat kit” with protective gear and equipment to do so safely. In the new protocol, an inpatient bat encounter prompts personnel to capture the bat and begin an investigation into known or potential occult exposure. Known or potential exposures merit submission of the bat for rabies testing, the results of which guide PEP recommendations. All encounters are investigated for point of entry or roost. Conclusions: Inpatient bat encounters are not uncommon. Encounters should prompt systematic assessment for exposures and an investigation of the root cause. Following a protocol may limit unnecessary PEP administration, prevent nosocomial transmission of rabies from bat to patient, and attenuate associated anxiety.

Funding: None

Disclosures: None
Middle East Respiratory Syndrome Coronavirus, Saudi Arabia, 2017 Outbreak: Super-Spreading Event and Control Measures
Authors: Amer Hala
Published: November 2020

Background: The hallmark of Middle East respiratory syndrome coronavirus (MERS-CoV) disease is the ability to cause major healthcare-associated outbreaks with superspreading events leading to massive transmission and excessive morbidity and mortality. This abstract provides overview of MERS-CoV multi-healthcare facilities outbreak in Riyadh in June 2017, with focus on cluster reported and the control measures taken at King Saud Medical City. The outbreak began with a patient who presented with acute renal failure requiring hemodialysis and became a MERS-CoV superspreader, igniting the cluster of cases in several hospitals in King Saud Medical City. Methods: For epidemiologic investigation, a case was defined as any patient with laboratory-confirmed MERS-CoV infection with connection to the affected healthcare facilities. Contact tracing and testing were performed according to the Ministry of Health (MOH) guidelines. MERS-CoV testing was recommended for HCWs who had unprotected close contact with a confirmed case. Considering the superspreading phenomena, contact tracing was included all persons attended the same area with the positive case either as a patient, an HCW, or a patient’s visitor or companion. Laboratory confirmation was conducted using real-time RT-PCR. Genome sequencing and phylogenetic analysis were performed for available MERS-CoV rRT-PCR–positive samples by the CDC. The infection control measures applied included decreasing patient load through downsizing emergency department acceptance, maintaining low elective services, limiting inpatient admissions, and encouraging discharge. Early detection and quarantining of any suspected cases took place through extensive contact tracing, properly triaging all patients upon admission, consistent monitoring of inpatients and HCWs for any emerging acute respiratory illness, allocation of more single rooms inside the facility and staff dormitory, and extending the services of virology laboratory to get timely results. Further measures consisted of extensive education on infection control practices, monitoring healthcare worker adherence, reassuring the public by maintaining transparency of published reports, and launching a hotline to respond to HCW concerns. Moreover, travel restrictions applied to any person with a history of exposure to a conﬁrmed MERS-CoV case during the 2-week monitoring period. Results: Overall, 44 cases of MERS-CoV infection were reported from 3 simultaneous clusters during the 2017 Riyadh outbreak, including 11 fatal cases. Among all of the cases, 29 cases were reported at King Saud Medical City. The outbreak at KSMC required 30 days to be controlled. Conclusions: High vigilance for early detection is a key control measure. To be more sensitive, point-of-care MERS-CoV testing is required because clinical suspicion is challenging in patients presenting with acute renal failure.

Funding: None

Disclosures: None
Minimum Healthcare Worker Influenza Immunization Rates Required to Decrease Influenza Transmission in Acute-Care Inpatients
Authors: Williams Victoria , Morgan Wendy , McGuire Maja , Katz Kevin , Leis Jerome
Published: November 2020

Background:
Annual influenza immunization of healthcare workers (HCWs) is widely recommended to reduce the risk of healthcare-associated influenza (HAI). Although there is a clear association between higher HCW immunization and reduced incidence of HAI, data in acute care are lacking compared to the nursing home setting. Objective: Our goal was to assess the association between HCW influenza immunization and the incidence of HAI across 2 acute-care facilities. Methods: A multicenter prospective cohort study was undertaken at 2 acute-care hospitals including 1 university and 1 community-based academic hospital. Any patient prospectively identified with HAI was included between 2013–2014 and 2018–2019, whereas 2017–2018 was excluded due to vaccine mismatch. The HCW influenza immunization rate was defined as the proportion of HCWs (nurses and other allied and support staff but excluding physicians) immunized prior to December 15. A case of HAI was defined as laboratory-confirmed influenza A or B with symptom onset >72 hours after admission. The association between inpatient ward HCW influenza immunization rate and the incidence of HAI was compared using a Poisson regression analysis adjusting for hospital and influenza season. Results: Over 5 influenza seasons, the incidences of HAI at either facility were 0.24 and 0.22 per 1,000 patient days, whereas the median HCW influenza immunization rates were 57.3% (IQR, 42.5%–66.4%) and 66.6% (IQR, 50.6%–76.8%), respectively. When adjusting for hospital and influenza season in the multivariate analysis, HCW influenza immunization rates of 65% and 70% were not associated with HAI incidence. In contrast, HCW influenza immunization rates ≥75% was associated with a trend toward reduced HAI (IRR, 0.65; 95% CI, 0.39–1.08; P = .096) whereas inpatient wards above 80% immunization had significantly lower risk of HAI (IRR, 0.28; 95% CI, 0.089–0.89; P = .03). Conclusions: The risk of HAI across 2 acute-care hospitals was significantly lower among inpatient wards achieving HCW influenza immunization rates >80%. Acute-care facilities should aim for this minimum HCW immunization rate to protect patients from the complications of HAI.

Funding: None

Disclosures: None
National Trends of Incidence of Catheter-Associated Urinary Tract Infections in Acute-Care Hospitals
Authors: Soe Minn , Li Qunna , Nkwata Allan , Dudeck Margaret , Edwards Jonathan
Published: November 2020

Background:
An indwelling urinary catheter is used in ~12%–16% of adult hospital inpatients during their hospitalization, which poses risks for acquiring a catheter-associated urinary tract infection (CAUTI). CAUTI data have been reported to the NHSN since 2005, and national benchmarks are annually reported in NHSN progress reports. Trends analyses in the incidence of CAUTI reported to the NHSN over long time have not been previously assessed. Objective: We investigated the national trends of CAUTI incidence separately for intensive care units (ICUs) and wards in acute-care hospitals (ACHs) from 2009 through 2018. Methods: We analyzed CAUTI data from ACHs reported to NHSN in 2009–2018. To evaluate trends of CAUTI incidence (per 1,000 catheter days), we conducted interrupted time-series analysis using negative-binomial mixed-effects modeling, separately for ICUs (nonneonatal ICUs) and wards. Due to the reporting requirement for adult and pediatric ICUs in 2012, and medical, surgical, and medical-surgical wards in 2015 by the CMS and the institution of the NHSN CAUTI definitional changes in 2015, calendar years 2012 and 2015 were treated as interruptions to the outcome in ICU models, and year 2015 was treated as a single interruption in the ward models. Regression models were assessed and adjusted, as appropriate, for patient care location type and facility-level characteristics such as hospital type, teaching status, bed size, number (and percentage) of ICU beds, and average length of inpatient stay. Random intercept and slope models were evaluated with covariance tests and were included to account for differential baseline incidence and trends among reporting hospitals. Results: The volume of patient care locations and hospitals reporting to the NHSN increased over time. Among the ICUs, the CAUTI incidence rate did not change in 2009–2012 and increased at an average of 5.6% per year in 2012–2014 (Fig. 1). CAUTI incidence rate dropped nearly 40% in 2015; thereafter, it decreased at an average of 8.9% per year. Among the wards, CAUTI incidence rate decreased at an average of 4.3% per year beginning 2009 (Fig. 2). The CAUTI incidence rate dropped almost 28% in 2015 and then decreased at an average of 4.3% per year. Conclusions: CAUTI incidence decreased substantially in 2015 among both ICUs and wards, which was partially attributable to CAUTI definitional change (see also Fig. 7 at https://www.cdc.gov/hai/data/archive/data-summary-assessing-progress.html). The significant decline of CAUTI incidence in both location types since 2015 is encouraging, and continued efforts in prevention of CAUTI are vital to sustaining this decline in the future.

Funding: None

Disclosures: None
Prediction of Surgical Risk in General Surgeries: Process Optimization Through Support Vector Machine (SVM) Algorithm
Authors: Souza Flávio , Couto Braulio , Silva Gabriel Henrique Silvestre da , Dias Igor Gonçalves , Rigueira Rafael Vieira Magno , Pimenta Gustavo Maciel , Martins Maurilio , Mendes Julio Cesar , Braga Gabriele Maria , Teixeira Jéssica Angelina , Santos Renata Carvalho , Martins Julia Maria Campos , Sousa Karla Silvia de , Souza Douglas Nascimento de , Alves Gustavo Barros , Rocha Vladimir Alexei Rodrigues
Published: November 2020

Background: In 5 hospitals in Belo Horizonte (population, 3 million) between July 2016 and June 2018, a survey was performed regarding surgical site infection (SSI). We statistically evaluated SSI incidents and optimized the power to predict SSI through pattern recognition algorithms based on support vector machines (SVMs). Methods: Data were collected on SSIs at 5 different hospitals. The hospital infection control committees (CCIHs) of the hospitals collected all data used in the analysis during their routine SSI surveillance procedures; these data were sent to the NOIS (Nosocomial Infection Study) Project. NOIS uses SACIH software (an automated hospital infection control system) to collect data from hospitals that participate voluntarily in the project. In the NOIS, 3 procedures were performed: (1) a treatment of the database collected for use of intact samples; (2) a statistical analysis on the profile of the hospitals collected; and (3) an assessment of the predictive power of SVM with a nonlinear separation process varying in configurations including kernel function (Laplace, Radial Basis, Hyperbolic Tangent and Bessel) and the k-fold cross-validation–based resampling process (ie, the use of data varied according to the amount of folders that cross and combine the evaluated data, being k = 3, 5, 6, 7, and 10). The data were compared by measuring the area under the curve (AUC; range, 0–1) for each of the configurations. Results: From 13,383 records, 7,565 were usable, and SSI incidence was 2.0%. Most patients were aged 35–62 years; the average duration of surgery was 101 minutes, but 76% of surgeries lasted >2 hours. The mean hospital length of stay without SSI was 4 days versus 17 days for the SSI cases. The survey data showed that even with a low number of SSI cases, the prediction rate for this specific surgery was 0.74, which was 14% higher than the rate reported in the literature. Conclusions: Despite the high noise index of the database, it was possible to sample relevant data for the evaluation of general surgery patients. For the predictive process, our results were >0.50 and were 14% better than those reported in the literature. However, the database requires more SSI case samples because only 2% of positive samples unbalanced the database. To optimize data collection and to enable other hospitals to use the SSI prediction tool, a mobile application was developed (available at www.sacihweb.com).

Funding: None

Disclosures: None
Prevalence of Drug-Resistant Mycobacterium tuberculosis in the Veterans Health Administration (VHA)
Authors: Oda Gina , Lucero-Obusan Cynthia , Schirmer Patricia , Holodniy Mark
Published: November 2020

Background: In 2018, the CDC reported that isoniazid (INH)-resistant and multidrug-resistant Mycobacterium tuberculosis (MDR-TB, ie, resistant to at least INH and rifampin) represented 9.3% and 1.5% of TB cases, respectively, in the United States. Objective: We analyzed the prevalence of drug-resistant TB within the Veterans Health Administration (VHA) to determine factors associated with hospitalization. Method: Patients were identified using Council of State and Territorial Epidemiologists case definition for laboratory-confirmed TB by querying VHA data sources from January 1, 2010, to June 30, 2019. Susceptibility results were included for isolates from all body sites. Using a 2-proportion z test, we compared the following demographic factors for susceptible versus drug-resistant TB: age, gender, race/ethnicity, location of residence and birth. We also assessed the following clinical and hospitalization factors: pulmonary versus extrapulmonary disease, latent TB infection (LTBI) screening and treatment, length of stay (LOS), intensive care unit (ICU) stay, and death. Results: In total, 878 patients had lab-confirmed TB, and 812 (92%) had electronic drug-susceptibility results available. Of 812 patients, 49 (6%) showed anti-TB drug resistance (Fig. 1), which was less than that reported nationally by the CDC (Fig. 2). No patients had extensively drug-resistant TB. Only 18 of 49 patients (37%) with resistant TB had LTBI screening ≥3 months prior to diagnosis. Among 6 patients with LTBI, 3 (50%) received treatment. Patient state of residence was the only demographic factor associated with resistant TB. Arizona, Iowa, Massachusetts, Montana, Nevada, South Dakota, and Utah were significantly associated with drug-resistant TB cases (P < .05); however, overall numbers of VHA TB cases in these states were low. Patients with resistant TB were more likely to have extrapulmonary TB (13 of 49, 26.5%) than patients with susceptible TB (111 of 763, 14.5%; P < .05) (Table 1). Mortality at 30 and 90 days for resistant versus susceptible TB cases did not differ significantly: 6.1% versus 5.1% at 30 days (P = .75) and 10.2% versus 10.6% at 90 days (P = 0.92), respectively. The proportion of drug-resistant TB cases hospitalized did not differ from susceptible cases (59% vs 63%), respectively (P = .62) nor did the proportion with ICU stay (14.3% vs 12.3%), respectively (P = .40). Median LOS for drug-resistant TB cases and susceptible cases were similar: 5 days (range, 0–303 versus 4 days (range, 0–111), respectively. Conclusions: Rates of drug-resistant TB are lower in the VHA than in the general US population. However, improvement is needed in LTBI screening and treatment rates. Little has been published on drug resistance in extrapulmonary TB; however, our findings should alert clinicians to the possibility of resistance in these challenging infections.

Funding: None

Disclosures: None
Quality of Hospital Infection Control Programs in Low- and Middle-income Countries: A National Survey
Authors: Alvim André , Gazzinell Gazzinell , Couto Braulio
Published: November 2020

Background: One of the strategies to reduce healthcare-associated infections (HAIs) and promote the quality of disease prevention and control actions is the creation of a hospital infection control program. This program is a set of deliberately and systematically developed actions aimed toward reducing the incidence and severity of infections to the maximum extent possible. In Brazil, studies on the subject still need to be improved; they focus on structural and process assessments, especially the survey of continuing education indicators as a quality requirement for the prevention of HAIs. The organizational context does not contribute to the success of the program, and difficulties remain in implementing recommendations and in implementing patient safety policies. Objective: To analyze hospital infection control programs in relation to quality components. Methods: This cross-sectional epidemiological study was conducted in health services located in the 5 official regions of Brazil: Midwest, Northeast, North, Southeast, and South. To select the study sites, nonprobabilistic sampling using the snowball technique was used. The potential study population consisted of 114 hospital infection control services. Health professionals responded to the structured instrument sent electronically via e-mail, and other health services near their locality, until reaching a national proportion. We used the “Hospital Infection Control Program Evaluation Questionnaire”; it consists of 36 multiple-choice questions. This tool was validated by 96 expert judges using the Cronbach’s alpha test (0.82) and the content validity index (0.88). A data analysis was performed using the multivariate principal component analysis technique (PCA). Results: Overall, 13 PCA components (Fig. 1) were used to build a score for measuring the performance of the hospital infection control program (ie, IQPC score). The Southern region had the best performance of the hospital infection control program (mi = 1.50; P = .02) (Fig. 2), private administration (mi = 0.45; P = .05), of hospitals that contained 300 beds or (mi = 1.38; P < .01), hospitals that used the NHSN criterion for HAI surveillance (mi = 2.12; P < .01), and those who searched prospective activity as a surveillance method (mi = 0.51; P < .01). Conclusions: The quality of nosocomial infection control programs still needs to be improved among health services, highlighting the need to invest in small, publicly managed hospitals that use retrospective active surveillance methods.

Funding: None

Disclosures: None
Real-Time Bedside Root Cause Analysis (RCA) as a Catalyst for Clostridioides difficile Reduction
Authors: Newman Hannah , Kirschenbaum Linda , Macyk Irene , Baker Daniel , Haas Janet C
Published: November 2020

Background:C. difficile infection has been a significant cause of morbidity and mortality over the past decade. Our hospital had rates of hospital-onset, laboratory-identified, C. difficile infection (HO-CDI) that were significantly higher than our state and national benchmarks. HO-CDI is defined as a test positive for C. difficile occurring on or after day 4 of hospitalization, regardless of the presence of symptoms. New leadership at the hospital sought a creative way to engage staff in finding solutions to our high rates of HO-CDI. Objective: The purpose of this intervention was to engage frontline staff in reporting and solving patient care situations that may increase infection risk to decrease HO-CDI rates. Methods: Starting in July 2015, real-time bedside RCAs were performed weekly for any HO-CDI on the unit to which the infection was attributed and on any unit from which the patient had been recently transferred. Top clinical leadership of the hospital, and all services and departments, physicians, nurses, and others involved with the patient’s care were expected to attend and identify factors that may have contributed to the infection. The findings were documented, and changes to care were made based on the findings. The rate of incident hospital onset HO-CDI per 10,000 patient days was used to measure outcome because standardized infection ratios for the period before 2016 were not available. Results: Staff members suggested 6 specific actions that were undertaken to decrease HO-CDI risk (Table 1). The HO-CDI rate during the preintervention period (2012–2014) was 6.85 per 10,000 patient days (275 cases). In the postintervention period (2016–2018) the HO-CDI rate was 3.13 per 10,000 patient days (101 cases). There was a 54% reduction in the HO-CDI rate in the postintervention period (P < .001). Conclusions: The multidisciplinary bedside RCA process resulted in staff providing recommendations for actions to reduce HO-CDI risk. Implementation of staff suggestions resulted in a sustained, significant decrease in HO-CDI.

Funding: None

Disclosures: None
The Dark Side of Executive Compensation Duration: Evidence from Mergers and Acquisitions
Authors: Li Zhi , Peng Qiyuan
Published: November 2020

We find that contrary to popular belief, CEOs with long compensation duration do not make better long-term investment decisions. Using a comprehensive pay duration measure, we find that acquisitions conducted by CEOs with long compensation duration receive more negative announcement returns, and experience significantly worse post-acquisition abnormal operating and stock performance, compared with deals conducted by CEOs with short compensation duration. The negative correlation between compensation duration and mergers and acquisitions (M&A) performance is driven by long-term time-vesting plans, not by performance-vesting plans. The results suggest that extending CEO pay horizons without implementing performance requirements is insufficient to improve managerial long-term investment decisions.
Drinking to the Future: Wine in Communist Bulgaria
Authors: Neuburger Mary
Published: November 2020

This article explores wine production, consumption and trade in the context of late socialist Bulgaria and the wider Eastern Bloc. In particular, it connects wine to the process of building legitimacy in Bulgaria, as part of post-Stalinist culture of consumer abundance and even connoisseurship that was steeped in nationalist narratives and meanings, as well as utopian visions of the future. To complicate such narratives, it also delves into the contradictory ways in which late-socialist anti-alcohol narratives and campaigns similarly looked to local, if not national, precursors to ground their counter model of a sober socialist present and communist future.
Uprooting Identity: European Integration, Political Realignment and the Wine of the Languedoc, 1984–2014
Authors: Smith Andrew WM
Published: November 2020

Uprooting productive vines transformed the landscape of the wine growing Languedoc as part of a coordinated European effort to reduce agricultural overproduction, most notably after 1984. The demographic shifts caused by this transformation upset regional political alliances, coinciding with a socialist presidency and electoral gains for the far-right Front National (FN). More traditional syndical bodies lost their ability to accent national change, floundering in the face of supra-national reform. This left space for political parties to politicise this gap between agency and power, and the FN retooled regional rhetoric emerging from wine protests on the left in service of local campaigns. Contextualising the election of Robert Ménard in Béziers in 2014, this article looks at how sectoral and economic transformation was passed over in favour of populist language borrowed from the vineyards only decades earlier, in which the uprooting of vines explains the perceived uprooting of identity.
‘Continental Connotations’: European Wine Consumption in 1970s Britain
Authors: Moss Stella
Published: November 2020

This article considers the significant increase in wine consumption in Britain in the period 1965–85. It explores the social and cultural meanings attached to wine through a case study analysis of Good Housekeeping, a women's magazine aimed at a mainly middle-class readership. The vast majority of wine consumed in Britain at this time was European, the appeal of which was, for many, rooted in an idealised evocation of continental sophistication. In illuminating the development of new socio-cultural habits, this article reveals the influence of continental tourism is bolstering enthusiasm for wine, as well as the impact of greater availability and affordability in popularising consumption.
3D microfluidic gradient generator for combination antimicrobial susceptibility testing
Authors: Sweet Eric , Yang Brenda , Chen Joshua , Vickerman Reed , Lin Yujui , Long Alison , Jacobs Eric , Wu Tinglin , Mercier Camille , Jew Ryan , Attal Yash , Liu Siyang , Chang Andrew , Lin Liwei
Published: November 2020

Microfluidic concentration gradient generators (µ-CGGs) have been utilized to identify optimal drug compositions through antimicrobial susceptibility testing (AST) for the treatment of antimicrobial-resistant (AMR) infections. Conventional µ-CGGs fabricated via photolithography-based micromachining processes, however, are fundamentally limited to two-dimensional fluidic routing, such that only two distinct antimicrobial drugs can be tested at once. This work addresses this limitation by employing Multijet-3D-printed microchannel networks capable of fluidic routing in three dimensions to generate symmetric multidrug concentration gradients. The three-fluid gradient generation characteristics of the fabricated 3D µ-CGG prototype were quantified through both theoretical simulations and experimental validations. Furthermore, the antimicrobial effects of three highly clinically relevant antibiotic drugs, tetracycline, ciprofloxacin, and amikacin, were evaluated via experimental single-antibiotic minimum inhibitory concentration (MIC) and pairwise and three-way antibiotic combination drug screening (CDS) studies against model antibiotic-resistant Escherichia coli bacteria. As such, this 3D µ-CGG platform has great potential to enable expedited combination AST screening for various biomedical and diagnostic applications.
Fabrication of on-chip probes for double-tip scanning tunneling microscopy
Authors: Leeuwenhoek Maarten , Groenewoud Freek , van Oosten Kees , Benschop Tjerk , Allan Milan P. , Gröblacher Simon
Published: November 2020

A reduction of the interprobe distance in multiprobe and double-tip scanning tunneling microscopy to the nanometer scale has been a longstanding and technically difficult challenge. Recent multiprobe systems have allowed for significant progress by achieving distances of ~30 nm using two individually driven, traditional metal wire tips. For situations where simple alignment and fixed separation can be advantageous, we present the fabrication of on-chip double-tip devices that incorporate two mechanically fixed gold tips with a tip separation of only 35 nm. We utilize the excellent mechanical, insulating and dielectric properties of high-quality SiN as a base material to realize easy-to-implement, lithographically defined and mechanically stable tips. With their large contact pads and adjustable footprint, these novel tips can be easily integrated with most existing commercial combined STM/AFM systems.
COVID-19-associated gastrointestinal and liver injury: clinical features and potential mechanisms
Authors: Zhong Peijie , Xu Jing , Yang Dong , Shen Yue , Wang Lu , Feng Yun , Du Chunling , Song Yuanlin , Wu Chaomin , Hu Xianglin , Sun Yangbai
Published: November 2020

Coronavirus disease-2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection is spreading globally and poses a huge threat to human health. Besides common respiratory symptoms, some patients with COVID-19 experience gastrointestinal symptoms, such as diarrhea, nausea, vomiting, and loss of appetite. SARS-CoV-2 might infect the gastrointestinal tract through its viral receptor angiotensin-converting enzyme 2 (ACE2) and there is increasing evidence of a possible fecal–oral transmission route. In addition, there exist multiple abnormalities in liver enzymes. COVID-19-related liver injury may be due to drug-induced liver injury, systemic inflammatory reaction, and hypoxia–ischemia reperfusion injury. The direct toxic attack of SARS-CoV-2 on the liver is still questionable. This review highlights the manifestations and potential mechanisms of gastrointestinal and hepatic injuries in COVID-19 to raise awareness of digestive system injury in COVID-19.
Microbial ecology of the newly discovered serpentinite-hosted Old City hydrothermal field (southwest Indian ridge)
Authors: Lecoeuvre Aurélien , Ménez Bénédicte , Cannat Mathilde , Chavagnac Valérie , Gérard Emmanuelle
Published: November 2020

Lost City (mid-Atlantic ridge) is a unique oceanic hydrothermal field where carbonate-brucite chimneys are colonized by a single phylotype of archaeal Methanosarcinales, as well as sulfur- and methane-metabolizing bacteria. So far, only one submarine analog of Lost City has been characterized, the Prony Bay hydrothermal field (New Caledonia), which nonetheless shows more microbiological similarities with ecosystems associated with continental ophiolites. This study presents the microbial ecology of the ‘Lost City’-type Old City hydrothermal field, recently discovered along the southwest Indian ridge. Five carbonate-brucite chimneys were sampled and subjected to mineralogical and geochemical analyses, microimaging, as well as 16S rRNA-encoding gene and metagenomic sequencing. Dominant taxa and metabolisms vary between chimneys, in conjunction with the predicted redox state, while potential formate- and CO-metabolizing microorganisms as well as sulfur-metabolizing bacteria are always abundant. We hypothesize that the variable environmental conditions resulting from the slow and diffuse hydrothermal fluid discharge that currently characterizes Old City could lead to different microbial populations between chimneys that utilize CO and formate differently as carbon or electron sources. Old City discovery and this first description of its microbial ecology opens up attractive perspectives for understanding environmental factors shaping communities and metabolisms in oceanic serpentinite-hosted ecosystems.
Blood-brain barrier associated tight junction disruption is a hallmark feature of major psychiatric disorders
Authors: Greene Chris , Hanley Nicole , Campbell Matthew
Published: November 2020

Major psychiatric disorders affect 25% of the population. While genetic and environmental risk factors have been identified, the underlying pathophysiology of conditions, such as schizophrenia, bipolar disorder and major depression remains largely unknown. Here, we show that endothelial associated tight junction components are differentially regulated at the blood-brain barrier (BBB) in distinct neuroanatomic regions of human donor brain tissues. Previous studies have shown associations between BBB disruption and the development of psychiatric behaviours in rodents. Using immunohistochemistry and qRT-PCR, we show that the expression of claudin-5 is reduced in the hippocampus of individuals diagnosed with major depression or schizophrenia. We also show that levels of tight junction mRNA transcripts, including claudin-5, claudin-12 and ZO-1 correlate with disease duration and age of onset of a range of psychiatric disorders. Together, these data show that BBB associated tight junction disruption and dysregulation is a common pathology observed across the major psychiatric disorders. Targeting and regulating tight junction protein integrity at the BBB could, therefore, represent a novel therapeutic strategy for these conditions.
Correction: Identification of a novel polymorphism associated with reduced clozapine concentration in schizophrenia patients—a genome-wide association study adjusting for smoking habits
Authors: Smith Robert Løvsletten , O’Connell Kevin , Athanasiu Lavinia , Djurovic Srdjan , Kringen Marianne Kristiansen , Andreassen Ole A. , Molden Espen
Published: November 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Blood pressure monitoring following individual carpules of anesthetic utilizing computer-controlled anesthetic delivery
Authors: Soileau Kristi M. , DeGenova Adam E. , Yu Qingzhao
Published: November 2020

To date, no study has evaluated blood pressure following administration of each carpule given for dental procedures using a computerized dental anesthesia system. Blood pressures taken prior to performing invasive periodontal procedures were compared with those readings measured following delivery of each of up to three consecutive carpules of Marcaine or Xylocaine in varying order. Pressure differences were also adjusted for age, sex, race, and whether a prescribed anxiolytic was taken beforehand. Neither systolic nor diastolic blood pressures changed significantly as compared to initial blood pressure readings. However, compared with Whites, Hispanics, and Middle Easterners, Blacks had significantly higher systolic pressure at the third carpule delivery, the cause being unknown. Blood pressure in patients being anesthetized for root planing and various periodontal surgical procedures will not increase significantly when administering up to three carpules, whether Marcaine or Xylocaine, in varying order, using controlled flow dental anesthesia, and this method may be preferable to syringes in managing dental procedural stress.
Interpretation of morphogen gradients by a synthetic bistable circuit
Authors: Grant Paul K. , Szep Gregory , Patange Om , Halatek Jacob , Coppard Valerie , Csikász-Nagy Attila , Haseloff Jim , Locke James C. W. , Dalchau Neil , Phillips Andrew
Published: November 2020

During development, cells gain positional information through the interpretation of dynamic morphogen gradients. A proposed mechanism for interpreting opposing morphogen gradients is mutual inhibition of downstream transcription factors, but isolating the role of this specific motif within a natural network remains a challenge. Here, we engineer a synthetic morphogen-induced mutual inhibition circuit in E. coli populations and show that mutual inhibition alone is sufficient to produce stable domains of gene expression in response to dynamic morphogen gradients, provided the spatial average of the morphogens falls within the region of bistability at the single cell level. When we add sender devices, the resulting patterning circuit produces theoretically predicted self-organised gene expression domains in response to a single gradient. We develop computational models of our synthetic circuits parameterised to timecourse fluorescence data, providing both a theoretical and experimental framework for engineering morphogen-induced spatial patterning in cell populations.
Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART
Authors: Wan Chenjie , Bachmann Nadine , Mitov Venelin , Blanquart François , Céspedes Susana Posada , Turk Teja , Neumann Kathrin , Beerenwinkel Niko , Bogojeska Jasmina , Fellay Jacques , Roth Volker , Böni Jürg , Perreau Matthieu , Klimkait Thomas , Yerly Sabine , Battegay Manuel , Walti Laura , Calmy Alexandra , Vernazza Pietro , Bernasconi Enos , Cavassini Matthias , Metzner Karin J. , Günthard Huldrych F. , Kouyos Roger D. ,   the Swiss HIV Cohort Study, Anagnostopoulos Alexia , Battegay Manuel , Bernasconi Enos , Böni Jürg , Braun Dominique L. , Bucher Heiner C. , Calmy Alexandra , Cavassini Matthias , Ciuffi Angela , Dollenmaier Günter , Egger Matthias , Elzi Luigia , Fehr Jan , Fellay Jacques , Furrer Hansjakob , Fux Christoph A. , Günthard Huldrych F. , Haerry David , Hasse Barbara , Hirsch Hans H. , Hoffmann Matthias , Hösli Irene , Huber Michael , Kahlert Christian , Kaiser Laurent , Keiser Olivia , Klimkait Thomas , Kouyos Roger D. , Kovari Helen , Ledergerber Bruno , Martinetti Gladys , de Tejada Begona Martinez , Marzolini Catia , Metzner Karin J. , Müller Nicolas , Nicca Dunja , Paioni Paolo , Pantaleo Guiseppe , Perreau Matthieu , Rauch Andri , Rudin Christoph , Scherrer Alexandra U. , Schmid Patrick , Speck Roberto , Stöckle Marcel , Tarr Philip , Trkola Alexandra , Vernazza Pietro , Wandeler Gilles , Weber Rainer , Yerly Sabine
Published: November 2020

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure.
Structural and electronic switching of a single crystal 2D metal-organic framework prepared by chemical vapor deposition
Authors: Claire F. James , Solomos Marina A. , Kim Jungkil , Wang Gaoqiang , Siegler Maxime A. , Crommie Michael F. , Kempa Thomas J.
Published: November 2020

The incorporation of metal-organic frameworks into advanced devices remains a desirable goal, but progress is hindered by difficulties in preparing large crystalline metal-organic framework films with suitable electronic performance. We demonstrate the direct growth of large-area, high quality, and phase pure single metal-organic framework crystals through chemical vapor deposition of a dimolybdenum paddlewheel precursor, Mo2(INA)4. These exceptionally uniform, high quality crystals cover areas up to 8600 µm2 and can be grown down to thicknesses of 30 nm. Moreover, scanning tunneling microscopy indicates that the Mo2(INA)4 clusters assemble into a two-dimensional, single-layer framework. Devices are readily fabricated from single vapor-phase grown crystals and exhibit reversible 8-fold changes in conductivity upon illumination at modest powers. Moreover, we identify vapor-induced single crystal transitions that are reversible and responsible for 30-fold changes in conductivity of the metal-organic framework as monitored by in situ device measurements. Gas-phase methods, including chemical vapor deposition, show broader promise for the preparation of high-quality molecular frameworks, and may enable their integration into devices, including detectors and actuators.
Dynamically-enhanced strain in atomically thin resonators
Authors: Zhang Xin , Makles Kevin , Colombier Léo , Metten Dominik , Majjad Hicham , Verlot Pierre , Berciaud Stéphane
Published: November 2020

Graphene and related two-dimensional (2D) materials associate remarkable mechanical, electronic, optical and phononic properties. As such, 2D materials are promising for hybrid systems that couple their elementary excitations (excitons, phonons) to their macroscopic mechanical modes. These built-in systems may yield enhanced strain-mediated coupling compared to bulkier architectures, e.g., comprising a single quantum emitter coupled to a nano-mechanical resonator. Here, using micro-Raman spectroscopy on pristine monolayer graphene drums, we demonstrate that the macroscopic flexural vibrations of graphene induce dynamical optical phonon softening. This softening is an unambiguous fingerprint of dynamically-induced tensile strain that reaches values up to ≈4 × 10−4 under strong non-linear driving. Such non-linearly enhanced strain exceeds the values predicted for harmonic vibrations with the same root mean square (RMS) amplitude by more than one order of magnitude. Our work holds promise for dynamical strain engineering and dynamical strain-mediated control of light-matter interactions in 2D materials and related heterostructures.
Efficient energy transfer mitigates parasitic light absorption in molecular charge-extraction layers for perovskite solar cells
Authors: Eggimann Hannah J. , Patel Jay B. , Johnston Michael B. , Herz Laura M.
Published: November 2020

Organic semiconductors are commonly used as charge-extraction layers in metal-halide perovskite solar cells. However, parasitic light absorption in the sun-facing front molecular layer, through which sun light must propagate before reaching the perovskite layer, may lower the power conversion efficiency of such devices. Here, we show that such losses may be eliminated through efficient excitation energy transfer from a photoexcited polymer layer to the underlying perovskite. Experimentally observed energy transfer between a range of different polymer films and a methylammonium lead iodide perovskite layer was used as basis for modelling the efficacy of the mechanism as a function of layer thickness, photoluminescence quantum efficiency and absorption coefficient of the organic polymer film. Our findings reveal that efficient energy transfer can be achieved for thin (≤10 nm) organic charge-extraction layers exhibiting high photoluminescence quantum efficiency. We further explore how the morphology of such thin polymer layers may be affected by interface formation with the perovskite.
All-optical adaptive control of quantum cascade random lasers
Authors: Schönhuber S. , Bachelard N. , Limbacher B. , Kainz M. A. , Andrews A. M. , Detz H. , Strasser G. , Darmo J. , Rotter S. , Unterrainer K.
Published: November 2020

Spectral fingerprints of molecules are mostly accessible in the terahertz (THz) and mid-infrared ranges, such that efficient molecular-detection technologies rely on broadband coherent light sources at such frequencies. If THz Quantum Cascade Lasers can achieve octave-spanning bandwidth, their tunability and wavelength selectivity are often constrained by the geometry of their cavity. Here we introduce an adaptive control scheme for the generation of THz light in Quantum Cascade Random Lasers, whose emission spectra are reshaped by applying an optical field that restructures the permittivity of the active medium. Using a spatial light modulator combined with an optimization procedure, a beam in the near infrared (NIR) is spatially patterned to transform an initially multi-mode THz random laser into a tunable single-mode source. Moreover, we show that local NIR illumination can be used to spatially sense complex near-field interactions amongst modes. Our approach provides access to new degrees of freedom that can be harnessed to create broadly-tunable sources with interesting potential for applications like self-referenced spectroscopy.