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Intro: Published data is limited in describing clinical features and disease burden of invasive Escherichia coli disease (IED). This study characterized bacteremic and non-bacteremic IED in relation to clinical features and multidrug resistance (MDR) of causative E. coli isolates. Methods: EXPECT-2 (NCT04117113) was a multinational, hospital-based, observational study that prospectively enrolled IED patients aged ≥60 years between October 2019 and January 2021. IED was defined by a positive E. coli culture from blood (bacteremic IED), a sterile body site or urine (non-bacteremic IED) in the presence of requisite criteria of Systemic Inflammatory Response Syndrome (SIRS), Sequential Organ Failure Assessment (SOFA), or quick SOFA (qSOFA). In-hospital mortality and IED-related medical encounters were assessed through 28 days following IED diagnosis. MDR was defined as acquired non-susceptibility to ≥1 antibiotic in ≥3 antimicrobial classes. Findings: The full analysis set included 193 bacteremic (80.4%) and 47 non- bacteremic (19.6%) patients. Patient demographics were balanced between bacteremic and non-bacteremic IED. The rates of patients with ≥2 SIRS criteria were comparable between bacteremic (64.8%) and non-bacteremic IED (70.2%). The rates of patients with the ≥2-point change in total SOFA score were comparable between bacteremic (62.2%) and non-bacteremic IED (53.2%). The rates of sepsis and septic shock were 75.0% and 11.4%, respectively, for bacteremic, and 83.3% and 7.1%, respectively, for non-bacteremic IED. The most common IED-related medical encounter was the emergency room both in patients with bacteremic (31.5%, [41/130]) and non-bacteremic IED (35.9%, [14/39]). Of 11 patients who died, 6 (54.5%) had bacteremic IED. Of 294 E. coli isolates with antimicrobial susceptibility testing collected from 238 patients, MDR rates were 34.7% (87/251) for bacteremic and 37.2% (16/43) for non-bacteremic isolates. Conclusion: IED manifested as severe infection, with approximately one-third of E. coli isolates displaying MDR. Bacteremic and non-bacteremic IED were characterized by similar clinical features and MDR phenotypes.

Abstract The strength of an organization’s culture is an important property that may have implications for organizational structure, performance, diversity, and inclusion, independent of its content. However, progress on conceptualizing and measuring cultural strength has been restricted so far. We propose a novel measure of an organization’s cultural strength as the negative average cross-entropy of its members’ mindshare distributions, defined on a support comprising a set of firm-specific cultural elements. Using descriptive text data produced by 2.9 million individuals in about 95 thousand US firms from the employee review website Glassdoor.com, we calculate our measure of organizational cultural strength using topic modeling and show that it behaves as theoretically expected: older, smaller, and more geographically concentrated firms have stronger organizational cultures. We also note some intriguing associations between organizational cultural strength, role differentiation, and gender imbalance within firms. Finally, we discuss opportunities for using this new measure to understand how organizations work more generally.

Abstract Genetic and epigenetic modifications of genes involved in the key regulatory pathways play a significant role in the pathophysiology and progression of multifactorial diseases. The present study is an attempt to identify single nucleotide variations (SNVs) at CpG sites of promoters of ACAT1, APOB, APOE, CYBA, FAS, FLT1, KSR2, LDLR, MMP9, PCSK9, PHOX2A, REST, SH2B3, SORT1 and TIMP1 genes influencing CpG island (CGI) existence and size associated with the pathophysiology of Diabetes mellitus, Coronary artery disease and Cancers. Promoter sequences located between −2000 to + 2000 bp were retrieved from the EPDnew database and predicted the CpG island using MethPrimer. Further, SNVs at CpG sites were accessed from NCBI, Ensembl while transcription factor (TF) binding sites were accessed using AliBaba2.1. CGI existence and size were determined for each SNV at CpG site with respect to wild type and variant allele by MethPrimer. A total of 200 SNVs at CpG sites were analyzed from the promoters of ACAT1, APOB, APOE, CYBA, FAS, FLT1, KSR2, LDLR, MMP9, PCSK9, PHOX2A, REST, SH2B3, SORT1 and TIMP1 genes. Of these, only 17 (8.5%) SNVs were found to influence the loss of CGI while 70 (35%) SNVs were found to reduce the size of CGI. It has also been found that 59% (10) of CGI abolishing SNVs are showing differences in binding of TFs. The findings of the study suggest that the candidate SNVs at CpG sites regulating CGI existence and size might influence the DNA methylation status and expression of genes involved in molecular pathways associated with several diseases. The insights of the present study may pave the way for new experimental studies to undertake challenges in DNA methylation, gene expression and protein assays.

Non-communicable disease (NCD), including cancer, disproportionately affect Low- and Middle-Income Countries (LMICs). This inequity is in part due to limitations of pathology services, both human and infrastructural. While significant improvements have been made to address these gaps, creative approaches that are mindful of regional priorities, cultural differences, and unique local challenges are needed. In this perspective, we will describe the implementation of telepathology services in sub-Saharan Africa (SSA) that serve as cornerstones for direct patient care, multi-disciplinary care coordination, research programs, and building human capacity through training. Models and challenges of system implementation, sustainability, and pathologist engagement will be discussed. Using disease and site-specific examples, we will suggest metrics for quality control and improvement initiatives that are critical for providing high-quality cancer registry data and necessary for future implementation of therapeutic and interventional clinical trials.

Records of relative paleointensity are subject to several sources of error. Temporal averaging due to gradual acquisition of magnetization removes high-frequency fluctuations, whereas random errors introduce fluctuations at high frequency. Both sources of error limit our ability to construct stochastic models from paleomagnetic observations. We partially circumvent these difficulties by recognizing that the largest affects occur at high frequency. To illustrate we construct a stochastic model from two recent inversions of paleomagnetic observations for the axial dipole moment. An estimate of the noise term in the stochastic model is recovered from a high-resolution inversion (CALS10k.2), while the drift term is estimated from the low-frequency part of the power spectrum for a long, but lower-resolution inversion (PADM2M). Realizations of the resulting stochastic model yield a composite, broadband power spectrum that agrees well with the spectra from both PADM2M and CALS10k.2. A simple generalization of the stochastic model permits predictions for the mean rate of magnetic reversals. We show that the reversal rate depends on the time-averaged dipole moment, the variance of the dipole moment and a slow timescale that characterizes the adjustment of the dipole toward the time-averaged value. Predictions of the stochastic model give a mean rate of 4.2 Myr−1, which is in good agreement with observations from marine magnetic anomalies.

Records of relative paleointensity are subject to several sources of error. Temporal averaging due to gradual acquisition of magnetization removes high-frequency fluctuations, whereas random errors introduce fluctuations at high frequency. Both sources of error limit our ability to construct stochastic models from paleomagnetic observations. We partially circumvent these difficulties by recognizing that the largest affects occur at high frequency. To illustrate we construct a stochastic model from two recent inversions of paleomagnetic observations for the axial dipole moment. An estimate of the noise term in the stochastic model is recovered from a high-resolution inversion (CALS10k.2), while the drift term is estimated from the low-frequency part of the power spectrum for a long, but lower-resolution inversion (PADM2M). Realizations of the resulting stochastic model yield a composite, broadband power spectrum that agrees well with the spectra from both PADM2M and CALS10k.2. A simple generalization of the stochastic model permits predictions for the mean rate of magnetic reversals. We show that the reversal rate depends on the time-averaged dipole moment, the variance of the dipole moment and a slow timescale that characterizes the adjustment of the dipole toward the time-averaged value. Predictions of the stochastic model give a mean rate of 4.2 Myr−1, which is in good agreement with observations from marine magnetic anomalies.

Ambiguity and semantic differences are each known to be independent sources of communication difficulty. However, we show using computational models that ambiguity can compensate for semantic differences across communicators. Given the heterogeneity of humans with which artificial systems interact, semantic differences will be the norm. Therefore each time a machine starts to communicate with a new user, our results suggest it will do well to start with a moderately ambiguous code in order to more effectively bridge semantic differences. We dub this the “adaptive ambiguity” hypothesis.

Meniscus injuries are highly prevalent, and both meniscus injury and subsequent surgery are linked to the development of post-traumatic osteoarthritis (PTOA). Although the pathogenesis of PTOA remains poorly understood, the inflammatory cytokine IL-1 is elevated in synovial fluid following acute knee injuries and causes degradation of meniscus tissue and inhibits meniscus repair. Dynamic mechanical compression of meniscus tissue improves integrative meniscus repair in the presence of IL-1 and dynamic tensile strain modulates the response of meniscus cells to IL-1. Despite the promising observed effects of physiologic mechanical loading on suppressing inflammatory responses of meniscus cells, there is a lack of knowledge on the global effects of loading on meniscus transcriptomic profiles. In this study, we compared two established models of physiologic mechanical stimulation, dynamic compression of tissue explants and cyclic tensile stretch of isolated meniscus cells, to identify conserved responses to mechanical loading. RNA sequencing was performed on loaded and unloaded meniscus tissue or isolated cells from inner and outer zones, with and without IL-1. Overall, results from both models showed significant modulation of inflammation-related pathways with mechanical stimulation. Anti-inflammatory effects of loading were well-conserved between the tissue compression and cell stretch models for inner zone; however, the cell stretch model resulted in a larger number of differentially regulated genes. Our findings on the global transcriptomic profiles of two models of mechanical stimulation lay the groundwork for future mechanistic studies of meniscus mechanotransduction, which may lead to the discovery of novel therapeutic targets for the treatment of meniscus injuries.

When we engage in the process of division of labor, there are typically multiple alternatives, but insufficient knowledge to choose among them. Under such conditions, we propose that not all alternatives are equally likely to be pursued. In particular, when we engage in the process of division of labor for novel and nonrepetitive production, we argue that we display a tendency to perceive and select object-based task partitions over activity-based partitions. We experimentally investigate how the salience of objects over activities manifests itself in individuals and groups engaged in division of labor for the assembly of strongly or weakly decomposable products. We draw implications for organization design as well as the impact of technological change on organizations. This paper was accepted by Jesper Sørensen, organizations.

Introduction: The middle rectal artery is a vital artery supplying the rectum, along with the superior and inferior rectal arteries. We explored the middle rectal artery due to its importance in rectal carcinoma surgeries. Methods: In total, 40 pelvises were obtained from the Department of Anatomy of Dr. D. Y. Patil Medical College in Pune City, India. Results: Variations were found in the origin of the middle rectal artery, including arising from the internal pudendal artery in 9 cases. In 2 cases, it was arising from the common stem of internal pudendal and inferior gluteal arteries. Arising from the inferior vesical artery was observed in 1 case; while in 2 cases, middle rectal artery was arising from the obturator artery. This is the artery that penetrates the fascia of rectum, which is essential in mesorectal excision in rectal carcinoma cases. It forms anastomosis with superior rectal artery. Conclusion: In the low anterior resection of the rectum, the middle rectal artery is always exposed.

Learning by doing, a change in beliefs (and consequently behaviour) due to experience, is crucial to the adaptive behaviours of organizations as well as the individuals that inhabit them. In this review paper, we summarise different pathologies of learning noted in past literature using a common underlying mechanism based on self-confirming biased beliefs. These are inaccurate beliefs about the environment that are self-confirming because acting upon these beliefs prevents their falsification. We provide a formal definition for self-confirming biased beliefs as an attractor that can lock learning by doing systems into suboptimal actions and provide illustrations based on simulations. We then compare and distinguish self-confirming biased beliefs from other related theoretical constructs, including confirmation bias, self-fulfilling prophecies, and sticking points, and underscore that self-confirming biased beliefs underlie inefficient self-confirming equilibria and hot-stove effects. Lastly, we highlight two fundamental ways to escape self-confirming biased beliefs: taking actions inconsistent with beliefs (i.e., exploration) and getting information on unchosen actions (i.e., counterfactuals).

Introduction: Apoptosis has been involved in a number of pathological conditions including Coronary Artery Disease (CAD). Caspases are important regulators and executioners in both extrinsic and intrinsic apoptotic pathways. Caspase 9 is an initiator caspase involved in intrinsic apoptotic pathway activated by mitochondrial damage and cytochrome c, forms an apoptosome with procaspase-9 and activates the CASP9 cascade to execute apoptosis. Aim: To evaluate the association between CASP9 (-1263G>A, -905T>G, -712C>T) genotypes/haplotypes and their susceptibility to CAD. Materials and Methods: This case-control study consisted of 300 CAD patients admitted in Durgabai Deshmukh Hospital and Research centre, Hyderabad, Telangana, India, along with 300 age and gender matched healthy controls from local population between January 2012 to December 2016. The DNA samples were genotyped for polymorphisms in CASP9 (-1263G>A, -905T>G, -712C>T) by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The data of CAD cases and controls were compared using the Student’s t-test for continuous variables and a Chi-square test for categorical variables using online statistical tools such as Interactive Chi square analysis and OpenEpi version 3.03. Linkage Disequilibrium (LD) and haplotype analysis were carried out by Haploview software. Interaction between single nucleotide polymorphisms and epidemiological parameters were determined by Multifactor Dimensionality Reduction (MDR) analysis. Results: Molecular analysis revealed that TG, TT genotypes of CASP9 -905T>G, -712C>T conferred 3 and 17 fold risk respectively for the development of CAD. Promoter polymorphic combinations of CASP9 were in perfect LD in controls. G-T-C, A-T-C haplotype of -1263G>A, -905T>G, -712C>T polymorphisms were found to be significantly predominant in the disease group. Further, MDR analysis showed that caspase 9 -712C>T polymorphism with positive family history, consumption of beverages and alcohol have high degree of redundancy. Conclusion: The present study suggests that CASP9 -712C>T variant might be used as a diagnostic marker for susceptibility to CAD.

Organ shortage is the greatest challenge facing the field of organ transplantation today. We aimed to study the attitude and knowledge toward organ donation among health-care professionals (HCPs) in rural India. The study was conducted in a rural town in Konkan region of Maharashtra in India. A questionnaire testing knowledge and attitude about various aspects of organ donation was distributed to HCPs. One hundred percent of the respondents were aware about organ donation. Nearly 40.6% and 21.9% believed that a healthy person and a cardiac dead person can be donors, respectively. Fifty percent believed that a brain dead person can be a donor and 3.1% clearly stated as to be having no idea regarding the health status of a donor. Almost 37.5% were ready to believe a heart beating person declared as “brain dead” as dead. Nearly 15.6% were ready to accept a brain dead person as “legally” dead. Highest awareness was observed regarding eye donation, i.e., 87.5%. High awareness was also observed regarding liver, kidney, heart, skin, and body donations, i.e., 78.1%, 65.6%, 37.5%, 31.3%, and 25.0%, respectively. Awareness regarding organ donation of other tissues and organs was poor. Nearly 46.9% HCPs stated that they felt need for an educational session on organ donation. Awareness regarding concept of organ donation among HCPs in rural India is high. Awareness regarding details of organ donation needs further awareness drives. There is a lack of understanding regarding various aspects of brain death and its importance in organ donation.

Organ shortage is the greatest challenge facing the field of organ transplantation today. We aimed to study the attitude and knowledge toward body and organ donation among people in rural India. The present study was conducted in a rural town called Lanja, in the Konkan region of Maharashtra in India. A questionnaire covering demographic data, knowledge, and attitude of the participants was distributed to 400 students, middle-aged and senior citizens; 91.5% of the respondents were aware about organ donation. Television (55.2%) and newspaper (45.8%) were the most popular sources of information. About 56.2% and 32.8% believed that a healthy person and a cardiac dead person can be donors, respectively. Nearly 29.4% believed that a brain-dead person can be a donor and 22.4% clearly stated as to be having no idea regarding the health status of a donor. Highest awareness was observed regarding eye donation (92%). High awareness was also observed regarding heart, kidney, and liver donations, that is, 71.1%, 61.2%, and 54.2%, respectively. Awareness regarding donation of other tissues and organs was poor. Only 46.8% believed that the family of the deceased person can give consent for organ donation if the donor had not signed the donor card. Awareness regarding both body and organ donation in rural India is high. However, there is lack of understanding regarding the concept of brain-death. Awareness regarding body and other organ and tissue donations besides eye, kidney, etc., needs further awareness drives.

Introduction Trauma is prevalent in the general population in various forms and has lasting effects on health. Physicians routinely examine patients who have experienced trauma, although most providers lack training in trauma-informed care, a well-established framework for providing quality care to trauma survivors. To address this gap, we implemented a novel curriculum on trauma-informed physical examination skills for first-year medical students. Methods We held a large-group lecture for 148 first-year medical students and 40 faculty members to introduce a framework for a trauma-informed physical examination, using a standardized patient for demonstration. The framework included specific language and behaviors to employ before, during, and after the examination in order to enhance patients' sense of safety, control, and trust. Students then transitioned to small groups to practice performing vital signs using a trauma-informed approach, with supervision from MD faculty. Results Five-point scales were used to evaluate students' knowledge gained from the session and satisfaction with the session. Overall satisfaction with the session was rated as 4.08 (SD = 0.81), and students felt that the session was highly effective in defining a trauma-informed physical examination (4.29, SD = 0.70). Discussion The session was well received and effective in teaching future physicians trauma-informed skills. We offer other institutions a model for incorporating trauma-informed care into clinical skills curricula.

Background Oxidative stress (OS) is a key characteristic feature in cancer initiation and progression. Among multiple cancers, NADPH oxidase (NOX) dependent free radical production is implicated in oxidative stress. P22phox, a subunit of NADPH oxidase encoded by the CYBA gene has functional polymorphisms associated with various complex diseases. The present study was aimed to examine the importance and association of the functional polymorphisms of CYBA gene (-930 A/G and 242 C/T) with the oxidative stress in breast cancer (BC) development and progression. Materials and Methods We have performed a case-control study on 300 breast cancer patients and 300 healthy individuals as controls to examine the role of CYBA gene -930 A/G and 242 C/T single nucleotide polymorphisms (SNPs) using As-PCR and PCR-RFLP assays and its association with OS as measured by plasma MDA levels. Linkage disequilibrium (LD) plots were generated using Haploviewtool and Multifactor dimensionality reduction (MDR) analysis was applied to assess high-order interactions between the SNPs. The Insilco analysis has been performed to predict the effect of SNPs on the gene regulation using online tools. Results We have found that genotype frequencies of CYBA gene -930 A/G and 242C/T polymorphism were significantly different between controls and BC patients (p

Extracellular matrix degradation by matrix metalloproteinases (MMPs) is an important mechanism involved in tumor invasion and metastasis. Genetic variations of MMPs have shown association with multiple cancers. The present study is focused to elucidate the association of MMP-1, 3 and 9 genetic variants with respect to epidemiological and clinicopathological variables by haplotype, LD, MDR, survival in silico analyses among South Indian women.MMP3-1171 5A/6A and MMP9-1562 C/T SNPs were genotyped by Allele specific polymerase chain reaction and MMP1-1607 1G/2G polymorphism by restriction fragment length polymorphism assays respectively, in 300 BC patients and age-matched 300 healthy controls. Statistical analysis was performed using the SNPStats and SPSS software. Linkage disequilibrium and gene-gene interactions were performed using Haploview and MDR software respectively. Further, transcription factor binding sites in the promoter regions of SNPs under study were carried out using AliBaba2.1 software.We have observed an increased frequency of 2G-allele of MMP1, 6A-allele of MMP3 and T-allele of MMP9 (p

Dorsal interossei are group of four intrinsic muscles of the hand that are of immense importance in its day-to-day functions. The finding of any variation related to these muscles is of significance from point of view of hand surgeons. In the present article, we report additional heads of dorsal interosseous muscle (DIM) in four upper limbs of a male cadavers. The muscles took origin from the dorsal surface of the adjacent metacarpal bones as well as from the distal row of carpal bones, had a belly separate from the two pennae of the DIM, distally joining the tendon of corresponding DIM. We discuss the anatomical details and clinical implications of this variation.

La publicación del Debate sobre “Cuerpos Humanos para la Enseñanza de la Anatomía: Importancia y Procuración – Experiencia con la Donación de Cadáveres” en el último número llamó la atención de la comunidad anatómica internacional por la amplitud del enfoque y la diversidad de las situaciones mencionadas. Aunque es posible encontrar muchos otros artículos sobre el tema, generalmente se enfocan a una experiencia particular, un país o, eventualmente, a un continente. Este Debate dio una breve visión sobre diferentes continentes y provesó un rápido punto de vista sobre los acuerdos y diversidad de problemas que afrontan los profesores de Anatomía en una amplia variedad de culturas. Tal como se especificó en la primera parte, los comentarios, consultas y respuestas de los participantes iniciales y los lectores en general serían considerados para una segunda parte del Debate. Todas las contribuciones significativas han sido organizadas e incluidas en esta instancia. Los lectores podrán encontrar información importante relativa a Australia, República Checa, Rusia, Turquía y Venezuela y comentarios adicionales a los conceptos previamente publicados sobre India, Malasia, Sudáfrica y Estados Unidos. Publication of the Debate on “Human Bodies to Teach Anatomy: Importance and Procurement – Experience with Cadaver Donation” in the immediate past issue called the attention of the international anatomic community because of the broad approach and the diversity of the mentioned situations. Instead it is possible to find many other articles on this topic they are usually focused on a particular experience, country or, eventually, a continent. This Debate gave a brief mapping on different continents and provided a quick point of view on agreements and diversity of problems afforded by the professors of Anatomy under a wide variety of cultures. As it was specified in the first part, comments, queries and answers from the initial participants and general readers should be considered as a second part of the Debate. All significant contributions have been organized and included in this instance. Readers may find important information related to Australia, Czech Republic, Russia, Turkey and Venezuela, and additional comments on the previous published concepts about India, Malaysia, South Africa and United States.