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OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.
Healthcare workers (HCWs) were at increased risk for mental health problems during the COVID-19 pandemic, with prior data suggesting women may be particularly vulnerable. Our global mental health study aimed to examine factors associated with gender differences in psychological distress and depressive symptoms among HCWs during COVID-19. Across 22 countries in South America, Europe, Asia and Africa, 32,410 HCWs participated in the COVID-19 HEalth caRe wOrkErS (HEROES) study between March 2020 and February 2021. They completed the General Health Questionnaire-12, the Patient Health Questionnaire-9 and questions about pandemic-relevant exposures. Consistently across countries, women reported elevated mental health problems compared to men. Women also reported increased COVID-19-relevant stressors, including insufficient personal protective equipment and less support from colleagues, while men reported increased contact with COVID-19 patients. At the country level, HCWs in countries with higher gender inequality reported less mental health problems. Higher COVID-19 mortality rates were associated with increased psychological distress merely among women. Our findings suggest that among HCWs, women may have been disproportionately exposed to COVID-19-relevant stressors at the individual and country level. This highlights the importance of considering gender in emergency response efforts to safeguard women’s well-being and ensure healthcare system preparedness during future public health crises.
To assess cost-effectiveness of late time-window endovascular treatment (EVT) in a clinical trial setting and a “real-world” setting.
Methods:
Data are from the randomized ESCAPE trial and a prospective cohort study (ESCAPE-LATE). Anterior circulation large vessel occlusion patients presenting > 6 hours from last-known-well were included, whereby collateral status was an inclusion criterion for ESCAPE but not ESCAPE-LATE. A Markov state transition model was built to estimate lifetime costs and quality-adjusted life-years (QALYs) for EVT in addition to best medical care vs. best medical care only in a clinical trial setting (comparing ESCAPE-EVT to ESCAPE control arm patients) and a “real-world” setting (comparing ESCAPE-LATE to ESCAPE control arm patients). We performed an unadjusted analysis, using 90-day modified Rankin Scale(mRS) scores as model input and analysis adjusted for baseline factors. Acceptability of EVT was calculated using upper/lower willingness-to-pay thresholds of 100,000 USD/50,000 USD/QALY.
Results:
Two-hundred and forty-nine patients were included (ESCAPE-LATE:n = 200, ESCAPE EVT-arm:n = 29, ESCAPE control-arm:n = 20). Late EVT in addition to best medical care was cost effective in the unadjusted analysis both in the clinical trial and real-world setting, with acceptability 96.6%–99.0%. After adjusting for differences in baseline variables between the groups, late EVT was marginally cost effective in the clinical trial setting (acceptability:49.9%–61.6%), but not the “real-world” setting (acceptability:32.9%–42.6%).
Conclusion:
EVT for LVO-patients presenting beyond 6 hours was cost effective in the clinical trial setting and “real-world” setting, although this was largely related to baseline patient differences favoring the “real-world” EVT group. After adjusting for these, EVT benefit was reduced in the trial setting, and absent in the real-world setting.
Despite replicated cross-sectional evidence of aberrant levels of peripheral inflammatory markers in individuals with major depressive disorder (MDD), there is limited literature on associations between inflammatory tone and response to sequential pharmacotherapies.
Objectives
To assess associations between plasma levels of pro-inflammatory markers and treatment response to escitalopram and adjunctive aripiprazole in adults with MDD.
Methods
In a 16-week open-label clinical trial, 211 participants with MDD were treated with escitalopram 10– 20 mg daily for 8 weeks. Responders continued on escitalopram while non-responders received adjunctive aripiprazole 2–10 mg daily for 8 weeks. Plasma levels of pro-inflammatory markers – C-reactive protein, Interleukin (IL)-1β, IL-6, IL-17, Interferon gamma (IFN)-Γ, Tumour Necrosis Factor (TNF)-α, and Chemokine C–C motif ligand-2 (CCL-2) - measured at baseline, and after 2, 8 and 16 weeks were included in logistic regression analyses to assess associations between inflammatory markers and treatment response.
Results
Pre-treatment levels of IFN-Γ and CCL-2 were significantly higher in escitalopram non-responders compared to responders. Pre-treatment IFN-Γ and CCL-2 levels were significantly associated with a lower of odds of response to escitalopram at 8 weeks. Increases in CCL-2 levels from weeks 8 to 16 in escitalopram non-responders were significantly associated with higher odds of non-response to adjunctive aripiprazole at week 16.
Conclusions
Pre-treatment levels of IFN-Γ and CCL-2 were predictive of response to escitalopram. Increasing levels of these pro-inflammatory markers may predict non-response to adjunctive aripiprazole. These findings require validation in independent clinical populations.
Active galactic nuclei (AGN) have been observed as far as redshift $z \sim 7$. They are crucial in investigating the early Universe as well as the growth of supermassive black holes at their centres. Radio-loud AGN with their jets seen at a small viewing angle are called blazars and show relativistic boosting of their emission. Thus, their apparently brighter jets are easier to detect in the high-redshift Universe. DES J014132.4–542749.9 is a radio-luminous but X-ray weak blazar candidate at $z = 5$. We conducted high-resolution radio interferometric observations of this source with the Australian Long Baseline Array at $1.7$ and $8.5$ GHz. A single, compact radio-emitting feature was detected at both frequencies with a flat radio spectrum. We derived the milliarcsecond-level accurate position of the object. The frequency dependence of its brightness temperature is similar to that of blazar sources observed at lower redshifts. Based on our observations, we can confirm its blazar nature. We compared its radio properties with those of two other similarly X-ray-weak and radio-bright AGN, and found that they show very different relativistic boosting characteristics.
Health is an important aspect of animal welfare, which is difficult to assess at herd level. Clinical examination of individual animals is time-consuming, and most measures of clinical herd health depend significantly on the examiner. Acute phase proteins are produced during inflammatory processes, and could therefore be used as general markers of infection and injury. Our objective was to evaluate whether haptoglobin could be used to monitor the health status of herds at slaughter.
107 groups of 20 slaughter pigs each were examined at two large abattoirs. Clinical signs of tail biting, lameness, injuries, abscesses, pneumonia, pleurisy, hepatitis and gastritis were recorded. The association between elevated haptoglobin concentration in meat juice samples and clinical signs was assessed via multiple logistic regression.
Pigs from groups in which tail biting, lameness, othaematomas, abscesses, pneumonia, pleurisy, pericarditis or condemnations of livers, lungs or carcasses occurred, showed higher levels of haptoglobin than pigs from slaughter groups without any of these clinical signs. In the multiple regression model, only the variables of lameness and tail biting were statistically significant. The haptoglobin test classified 66% of all slaughter groups correctly according to the presence of these clinical signs. These results demonstrate the potential for haptoglobin to be used as a screening test to identify problem herds at slaughter.
To maintain and enhance cow productivity and welfare, it is important that we can accurately assess and understand how cows respond to the physiological demands of gestation and lactation. Several methods have been developed for assessing the physiological responses to stressors and for detecting distress in cattle. Heart rate (HR) variability (HRV) is a non-invasive measure of autonomic nervous system activity and consequently a component of the physiological response to stress. In cattle, HRV has been successfully used to measure autonomic responses to a variety of health conditions and management procedures. The objectives of this study were to determine whether, among commercial Holstein Friesian cows and across farms, relationships exist between cow-level factors, HR and HRV. HRV parameters were compared with production records for 170 randomly selected, Holstein-Friesian-cows on 3 commercial dairy farms. Production data included parity, days in milk (DIM), milk yield, somatic cell count (SCC), % butterfat and protein, body condition score (BCS) and genetic indices. Fixed-effect, multivariable linear regression models were constructed to examine the association between cow-level variables and HRV parameters. Statistically significant relationships were found between HR and farm, temperature and BCS, and between HRV parameters and farm, rectal temperature, BCS, DIM, and percentage butterfat. Given the significant association between farms and several of the indices measured, it is recommended that care must be taken in the interpretation of HRV studies that are conducted on animals from a single farm. The current study indicated that within clinically normal dairy cattle HRV differed with the percentage of butterfat and BCS. Based on the relationships reported previously between HRV and stress in dairy cattle these results suggest that stress may be increased early in lactation, in cows with BCS <2.75 that are producing a high percentage of butterfat milk. Future work could focus on the physiological mechanisms through which these factors and their interactions alter HRV and how such physiological stress may be managed within a commercial farm setting.
We present and briefly discuss results of several studies of the source J2102+6015 with tentatively defined redshift z = 4.575 which demonstrates unusual properties in imaging and astrometric VLBI observations. Its properties might be considered as indications on the supermassive black hole binary which can be considered as a so far rare example of a high-redshift source of known electromagnetic and, possibly, predictable gravitational wave emissions.
Despite therapeutic advances, we still have difficulties in predicting response to treatment in bipolar disorder (BD). Brain-Derived Neurotrophic Factor (BDNF) has been put forward as a potential peripheral marker of treatment response.
Objective
To prospectively study the relation between clinical response to treatment and serum BDNF levels.
Aims
To investigate a) a possible association between serum BDNF levels and clinical response along 16 week follow-up and b) the role of val66met polymorphism in clinical response in a sample of drug-free patients with BD going through a mood episode.
Methods
This is a naturalistic, open-label prospective nested case control study matched for age, gender and ethnicity. Patients were 18 years or older, required BD diagnosis, undergoing a current manic, mixed or depressive episode and be off-medication for at least 2 weeks. Clinical assessment and blood withdrawn were conducted along follow-up. At the end of the study, patients were classified according to clinical response.
Results
25 of 36 (69.4%) of the patients were female and the mean age was 37.8 (SD 11.8) years old. Baseline serum BDNF levels did not show any difference between patients and controls (p = 0.075).There was a significant negative correlation between differences in serum BDNF levels and in CGI score along follow-up (r = −.372, p = 0.028). Serum BDNF levels were significant higher in responders compared to non-responders at week 4, 8 and 16 (p = 0.026, p = 0.009, p = 0.001 respectively). Val66met polymorphism did not seem to interfere in clinical response.
Conclusions
Changes in serum BDNF levels may help in monitoring treatment response.
The observance of possible somatic and environmental causes is essential to improve safety and efficacy in the treatment of agitated states. Severe agitation is considered a medical emergency requiring immediate psychopharmacologic intervention.
Objectives
To establish a clinically applicable consensus statement based on evidence- as well as eminence-based medicine with respect to schizophrenia and mania.
Methods
The recommendations given are based on information from psychopharmacologic treatment studies as well as logistic and practical factors intrinsic to clinical settings.
Results
Atypical antipsychotics given orally together with Lorazepam are considered the first-line treatment of agitated states in psychotic patients. Adequate communication with the patient is considered essential for effective oral administration. A novel alternative, Loxapine 4.5 mg or 9.1 mg (approved by the EMA 2013), is administered via an inhaler and exerts its sedative effects within 10 minutes. Inhalation may carry the benefit of greater patient acceptance. In contrast, intramuscular administration of antipsychotics is typically perceived by patients to be more invasive and persuasion or coercion may be necessary in severely ill patients. On the other hand, Aripiprazole, Haloperidole, Olanzapine and Ziprasidone show clinical efficacy within 15-30 minutes in psychopharmacologic trials when administered intramuscularly (i.m.). When taking extrapyramidal symptoms, QTc-prolongation and potential for combination with benzodiazepines into account, Aripiprazole i.m. carries the highest recommendation grade. Lorazepam may be administered intravenously. Currently, no antipsychotics are approved for intravenous administration.
Conclusion
This project gives recommendations which consider risk-benefit ratios and patient compliance.
Although discussed controversially, coercive practices during involuntary admission are common in mental health services. The impact of physical restraints on patients has not been sufficiently studied.
Aims
To investigate the subjective perception of patients during and after physical restraint.
Method
47 patients in a psychiatric intermediate care facility experiencing belt fixation were interviewed and filled out self-assessment forms at 4 visits.
Results
The median duration of restraint was 99 hours. Median VAS scores indicated moderate levels of anxiety. With increasing time span from the fixation, memory regarding this event decreased and patients experienced a regain of self-control. Consistently, 50% perceived high levels of coercion at admission, PTSD could be supposed in 25% of the patients.
Conclusion
Despite a considerable restraint of freedom, distress related to belt-fixation seems acceptable in our sample. Patients’ disapproval concerning restraint measures seems to diminish with time, probably related to decreasing memory regarding the fixation practice.
In his Generalization in Ethics, Marcus Singer distinguishes between individual and collective consequences. According to Singer, the collective consequences of everyone's acting in a certain way is for certain kinds of acts not the sum of—or, more exactly, is greater than the sum of—the individual consequences of each individual act. The point is put more straightforwardly by Sir Roy Harrod:
There are certain acts which when performed on n similar occasions have consequences more than n times as great as those resulting from one performance . ... For example, it may well happen that the loss of confidence due to a million lies uttered within certain limits of time and space is much more than a million times as great as the loss due to any one in particular.
The doctrine of double effect (hereafter abbreviated to DDE) is a principle of conduct that allows its adherents in certain difficult cases, provided certain conditions are satisfied, to bring about an effect indirectly that they are forbidden to bring about directly. By ‘indirectly', I mean that the effect in question is aimed at neither as an end in itself nor as a means to an end. In terms of Bentham's distinction between ‘oblique’ and ‘direct’ intention, DDE may be characterized as the thesis that, in certain difficult cases, provided certain conditions are satisfied, one may bring about (it is permissible to bring about) by oblique intention, as the merely foreseen consequence of an act, what one may not directly intend, either as end or as means.
The conditions in question are four, and failure to satisfy any one of them ensures the inapplicability of DDE to a particular situation. The first condition is that the act to be done, considered in itself and apart from its consequences, must not be intrinsically wrong.
Proglacial environments are ideal for studying the development of soils through the changes of rocks exposed by glacier retreat to weathering and microbial processes. Carbon (C) and nitrogen (N) contents as well as soil pH and soil elemental compositions are thought to be dominant factors structuring the bacterial, archaeal and fungal communities in the early stages of soil ecosystem formation. However, the functional linkages between C and N contents, soil composition and microbial community structures remain poorly understood. Here, we describe a multivariate analysis of geochemical properties and associated microbial community structures between a moraine and a glaciofluvial outwash in the proglacial area of a High Arctic glacier (Longyearbreen, Svalbard). Our results reveal distinct differences in developmental stages and heterogeneity between the moraine and the glaciofluvial outwash. We observed significant relationships between C and N contents, δ13Corg and δ15N isotopic ratios, weathering and microbial abundance and community structures. We suggest that the observed differences in microbial and geochemical parameters between the moraine and the glaciofluvial outwash are primarily a result of geomorphological variations of the proglacial terrain.
An updated compilation of published and new data of major-ion (Ca, Cl, K, Mg, Na, NO3, SO4) and methylsulfonate (MS) concentrations in snow from 520 Antarctic sites is provided by the national ITASE (International Trans-Antarctic Scientific Expedition) programmes of Australia, Brazil, China, Germany, Italy, Japan, Korea, New Zealand, Norway, the United Kingdom, the United States and the national Antarctic programme of Finland. The comparison shows that snow chemistry concentrations vary by up to four orders of magnitude across Antarctica and exhibit distinct geographical patterns. The Antarctic-wide comparison of glaciochemical records provides a unique opportunity to improve our understanding of the fundamental factors that ultimately control the chemistry of snow or ice samples. This paper aims to initiate data compilation and administration in order to provide a framework for facilitation of Antarctic-wide snow chemistry discussions across all ITASE nations and other contributing groups. The data are made available through the ITASE web page (http://www2.umaine.edu/itase/content/syngroups/snowchem.html) and will be updated with new data as they are provided. In addition, recommendations for future research efforts are summarized.
Deriving glacier outlines from satellite data has become increasingly popular in the past decade. In particular when glacier outlines are used as a base for change assessment, it is important to know how accurate they are. Calculating the accuracy correctly is challenging, as appropriate reference data (e.g. from higher-resolution sensors) are seldom available. Moreover, after the required manual correction of the raw outlines (e.g. for debris cover), such a comparison would only reveal the accuracy of the analyst rather than of the algorithm applied. Here we compare outlines for clean and debris-covered glaciers, as derived from single and multiple digitizing by different or the same analysts on very high- (1 m) and medium-resolution (30 m) remote-sensing data, against each other and to glacier outlines derived from automated classification of Landsat Thematic Mapper data. Results show a high variability in the interpretation of debris-covered glacier parts, largely independent of the spatial resolution (area differences were up to 30%), and an overall good agreement for clean ice with sufficient contrast to the surrounding terrain (differences ∼5%). The differences of the automatically derived outlines from a reference value are as small as the standard deviation of the manual digitizations from several analysts. Based on these results, we conclude that automated mapping of clean ice is preferable to manual digitization and recommend using the latter method only for required corrections of incorrectly mapped glacier parts (e.g. debris cover, shadow).
Field data from Stillberg (Switzerland), provided by SFISAR, have been analysed in order to understand the spatial distribution of snow transported by wind in avalanche-starting zones. The results have been used to develop a new empirical model for snowdrift distribution. This model constitutes the “snow-wind module” of the knowledge-based computer system called ELSA.
The model is based on an empirical parameter called the wind or “aeolien” coefficient. It represents the relation between two snow heights at a given place: the snow accumulated at the end of a wind period (or wind episode) and the snow available for transport at the beginning of the wind period. The wind coefficient has been established using field data from the Stillberg site.
Skin and soft tissue infections (SSTIs) due to Staphylococcus aureus have become increasingly common in the outpatient setting; however, risk factors for differentiating methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA) SSTIs are needed to better inform antibiotic treatment decisions. We performed a case-case-control study within 14 primary-care clinics in South Texas from 2007 to 2015. Overall, 325 patients [S. aureus SSTI cases (case group 1, n = 175); MRSA SSTI cases (case group 2, n = 115); MSSA SSTI cases (case group 3, n = 60); uninfected control group (control, n = 150)] were evaluated. Each case group was compared to the control group, and then qualitatively contrasted to identify unique risk factors associated with S. aureus, MRSA, and MSSA SSTIs. Overall, prior SSTIs [adjusted odds ratio (aOR) 7·60, 95% confidence interval (CI) 3·31–17·45], male gender (aOR 1·74, 95% CI 1·06–2·85), and absence of healthcare occupation status (aOR 0·14, 95% CI 0·03–0·68) were independently associated with S. aureus SSTIs. The only unique risk factor for community-associated (CA)-MRSA SSTIs was a high body weight (⩾110 kg) (aOR 2·03, 95% CI 1·01–4·09).