Background. There is limited knowledge of the key determinants of antimicrobial prescribing behavior (APB) in hospitals. An understanding of these determinants is required for the successful design, ...adoption, and implementation of quality improvement interventions in antimicrobial stewardship programs. Methods. Qualitative semistructured interviews were conducted with doctors (n = 10), pharmacists (n = 10), and nurses and midwives (n = 19) in 4 hospitals in London. Interviews were conducted until thematic saturation was reached. Thematic analysis was applied to the data to identify the key determinants of antimicrobial prescribing behaviors. Results. The APB of healthcare professionals is governed by a set of cultural rules. Antimicrobial prescribing is performed in an environment where the behavior of clinical leaders or seniors influences practice of junior doctors. Senior doctors consider themselves exempt from following policy and practice within a culture of perceived autonomous decision making that relies more on personal knowledge and experience than formal policy. Prescribers identify with the clinical groups in which they work and adjust their APB according to the prevailing practice within these groups. A culture of "noninterference' in the antimicrobial prescribing practice of peers prevents intervention into prescribing of colleagues. These sets of cultural rules demonstrate the existence of a "prescribing etiquette," which dominates the APB of healthcare professionals. Prescribing etiquette creates an environment in which professional hierarchy and clinical groups act as key determinants of APB. Conclusions. To influence the antimicrobial prescribing of individual healthcare professionals, interventions need to address prescribing etiquette and use clinical leadership within existing clinical groups to influence practice.
Full text
Available for:
BFBNIB, NUK, PNG, UL, UM, UPUK
IN SPITE OF PRISON Sanchez, Angel E.
Harvard law review,
04/2019, Volume:
132, Issue:
6
Journal Article
Peer reviewed
How does a former gang-banging, gun-toting Latino serving a thirty year prison sentence, the product of an elderly uneducated immigrant father and a drug-addicted mother, go from a prison cell to law ...school? It was not because of prison, but in spite of it.
Full text
Available for:
BFBNIB, DOBA, IZUM, KILJ, NMLJ, NUK, PILJ, PNG, PRFLJ, SAZU, UILJ, UKNU, UL, UM, UPUK
The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like ...growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Most aldosterone-producing adenomas (APAs) have gain-of-function somatic mutations of ion channels or transporters. However, their frequency in aldosterone-producing cell clusters of normal adrenal ...gland suggests a requirement for codriver mutations in APAs. Here we identified gain-of-function mutations in both CTNNB1 and GNA11 by whole-exome sequencing of 3/41 APAs. Further sequencing of known CTNNB1-mutant APAs led to a total of 16 of 27 (59%) with a somatic p.Gln209His, p.Gln209Pro or p.Gln209Leu mutation of GNA11 or GNAQ. Solitary GNA11 mutations were found in hyperplastic zona glomerulosa adjacent to double-mutant APAs. Nine of ten patients in our UK/Irish cohort presented in puberty, pregnancy or menopause. Among multiple transcripts upregulated more than tenfold in double-mutant APAs was LHCGR, the receptor for luteinizing or pregnancy hormone (human chorionic gonadotropin). Transfections of adrenocortical cells demonstrated additive effects of GNA11 and CTNNB1 mutations on aldosterone secretion and expression of genes upregulated in double-mutant APAs. In adrenal cortex, GNA11/Q mutations appear clinically silent without a codriver mutation of CTNNB1.
Full text
Available for:
GEOZS, IJS, IMTLJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZAGLJ
•The use of nSi reduces the workability of SCC due to its high water demand.•The greater the quantity of nSi the greater is the demand of superplasticizer additive.•The use of mSi and nSi increased ...the compressive strength of the SCC.•The greater compressive strength value was obtained by ternary mixture made with 2.5% of mSi and 2.5% of nSi.•The main part of the hydration of the cement in mixtures with nSi occurs before seven days.
Self-compacting concrete (SCC) has experienced significant development in the light of results obtained from numerous studies due to a series of advantages that it offers. The use of mineral admixtures at microscale and recently at nanoscale has permitted high-performance SCC to be obtained. Over the past few years, micro silica (mSi) and nano silica (nSi) have been the most used admixtures in continuing research into the areas of civil and agricultural engineering. This paper examines the behavior of 10 mixtures of SCC prepared with binary and ternary dosages through use of Portland cement (CEM I 52.5 R), mSi and nSi. As a reference, a SCC was designed which used no mineral admixtures, with the rest of the dosages using different percentages of mSi and nSi. Three were made with 2.5%, 5% and 7.5% of nSi; three more with 2.5%, 5% and 7.5% of mSi, and the remaining three by using both admixtures (ternary mixtures) mSi and nSi, with percentages of 2.5%/2.5%, 5%/2.5% and 2.5%/5%. The properties studied are rheological (flow test, funnel test and box test), mechanical (compressive strength, tensile strength and modulus of elasticity), and microstructural (hydration composites). According to the results obtained, all the concretes meet the requirements to be classified as SCCs by monitoring the quantity of superplasticizer additive according to the type and quantity of mineral admixture used. The higher compressive strength value was obtained by the ternary mixture with 2.5%/2.5% of mSi and nSi both at 28 and 90 days. Ternary mixtures of 2.5%/5% and 5%/2.5% reach values similar to those obtained by the mixture with 7.5% of nSi. Based on these results, it is possible to say that the compressive strength depends on the particle size and the amount of the admixture, and the particle-size distribution of the resulting mixture. This allows the advantage of obtaining considerably high compressive strength by using lower amounts both of nSi and of mSi and, therefore, of SP.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
Cultural and social determinants influence antibiotic decision-making in hospitals. We investigated and compared cultural determinants of antibiotic decision-making in acute ...medical and surgical specialties.
Methods
An ethnographic observational study of antibiotic decision-making in acute medical and surgical teams at a London teaching hospital was conducted (August 2015–May 2017). Data collection included 500 hours of direct observations, and face-to-face interviews with 23 key informants. A grounded theory approach, aided by Nvivo 11 software, analyzed the emerging themes. An iterative and recursive process of analysis ensured saturation of the themes. The multiple modes of enquiry enabled cross-validation and triangulation of the findings.
Results
In medicine, accepted norms of the decision-making process are characterized as collectivist (input from pharmacists, infectious disease, and medical microbiology teams), rationalized, and policy-informed, with emphasis on de-escalation of therapy. The gaps in antibiotic decision-making in acute medicine occur chiefly in the transition between the emergency department and inpatient teams, where ownership of the antibiotic prescription is lost. In surgery, team priorities are split between 3 settings: operating room, outpatient clinic, and ward. Senior surgeons are often absent from the ward, leaving junior staff to make complex medical decisions. This results in defensive antibiotic decision-making, leading to prolonged and inappropriate antibiotic use.
Conclusions
In medicine, the legacy of infection diagnosis made in the emergency department determines antibiotic decision-making. In surgery, antibiotic decision-making is perceived as a nonsurgical intervention that can be delegated to junior staff or other specialties. Different, bespoke approaches to optimize antibiotic prescribing are therefore needed to address these specific challenges.
Culture and team dynamics within specialties influence antibiotic decision-making. A collectivist culture in medicine supports rationalized and policy-driven decision-making. In surgery, antibiotic decision-making is delegated to juniors or other specialties. Addressing these specific challenges is critical to optimizing antibiotic prescribing.
•Mouse anti-human CYP11B1 and rat anti-human CYP11B2 monoclonal antibodies were made.•CYP11B2 is expressed in scattered cells and clusters called APCC.•CYP11B1 and CYP11B2 enzymes do not co-localize ...in the normal adrenal cortex.•CYP11B1 and 17α-hydroxylase co-localize in cells of the zona fasciculata.
1.The final enzymes in the biosynthesis of aldosterone and cortisol are by the cytochrome P450 CYP11B2 and CYP11B1, respectively. The enzymes are 93% homologous at the amino acid level and specific antibodies have been difficult to generate.2.Mice and rats were immunized with multiple peptides conjugated to various immunogenic proteins and monoclonal antibodies were generated. The only peptide sequences that generated specific antibodies were amino acids 41–52 for the CYP11B2 and amino acids 80–90 for the CYP11B1 enzyme.3.The mouse monoclonal CYP11B2-41 was specific and sensitive for use in western blots and produced specific staining of the zona glomerulosa of normal adrenal glands. The rat monoclonal CYP11B1-80 also detected a single band by western blot and detected only the zona fasciculata. Triple immunofluorescence of the adrenal demonstrated that the CYP11B1 and the CYP11B2 did not co-localize, while as expected the CYP11B1 co-localized with the 17α-hydroxylase.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Loss of E-cadherin is a key initial step in the transdifferentiation of epithelial cells to a mesenchymal phenotype, which occurs when tumor epithelial cells invade into surrounding tissues. ...Expression of the nuclear factor ZEB1 induces an epithelial-to-mesenchymal transition and confers a metastatic phenotype on carcinomas by repressing the E-cadherin gene at the transcriptional level. In this study, we show that ZEB1 interacts with the SWI/SNF chromatin-remodeling protein BRG1 to regulate E-cadherin independently of CtBP, its traditional co-repressor. Blocking the interaction between ZEB1 and BRG1 induces expression of E-cadherin and downregulation of the mesenchymal marker vimentin. ZEB1 and BRG1 colocalize in E-cadherin-negative cells from cancer lines and in the stroma of normal colon. Colocalization of ZEB1 and BRG1 in epithelial cells is only found in those de-differentiated cells characterized by nuclear beta-catenin staining at the invasive edge of the tumor. Our results identify ZEB1/BRG1 as a new transcriptional mechanism regulating E-cadherin expression and epithelial-to-mesenchymal transdifferentiation that may be involved during the initial stages of tumor invasion.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
En las sociedades desarrolladas existe una aceleración secular del crecimiento. Entre los años 2000 y 2004 hemos valorado el crecimiento en una población caucásica española procedente de Andalucía, ...Barcelona, Bilbao y Zaragoza y hemos comparado los resultados con estudios españoles realizados antes de 1988 en poblaciones caucásicas de Bilbao (BIB 88) y Cataluña (CAT 87).
Estudio transversal que valora el peso, la longitud y el índice de masa corporal (IMC) en 32.064 sujetos (16.607 varones y 15.457 mujeres) desde el nacimiento a la talla adulta: a) 5.796 son recién nacidos a término (2.974 varones y 2.822 mujeres) hijos de madres sanas, de gestaciones únicas; b) 23.701 son niños y adolescentes (12.358 varones y 11.343 mujeres) de 0,25 a 18 años de edad ambos inclusive, y c) 2.567 son adultos jóvenes (1.275 varones y 1.292 mujeres) de 18,1 a 24 años de edad. Todos estaban sanos, eran de raza caucásica y sus padres, de origen español. La distribución percentilada, el valor z-score y el diseño de las gráficas se ha realizado según el método LMS.
Se expresan los valores de la media, desviación estándar, coeficiente de Skewness y percentiles desde el nacimiento la edad adulta, en intervalos de 0,25-0,50 años. Existe un dimorfismo sexual y un incremento en los valores de peso y talla de todos los percentiles respecto a los estudios BIB 88 y CAT 87. Los valores de los percentiles 3, 50 y 97 de la talla adulta son superiores en 1,8, 1,4 y 3,3 cm respecto a BIB 88, y en 2,5, 3,3 y 3,8 cm respecto a CAT 87 en los varones, y 3,5, 2,5 y 4,2 cm respecto a BIB 88 y 3,5, 3,1 y 3,9 cm respecto a CAT 87 en las mujeres. Los correspondientes valores de peso son 5,4, 6,2 y 11,7 kg superiors a los de BIB 88 y 6,7, 6,3 y 10,1 kg superiores a los de CAT 87 en los varones y 1,7, 2,2 y 8,3 kg superiores a los de BIB 88, y 1,8, 2,4 y 3,6 kg superiores CAT 87 en las mujeres. Los respectivos incrementos en el IMC son 2,0, 1,4 y 3,9 respecto a BIB 88 y −0,1, −0,2 y 5,3 respecto a CAT 87 en los varones y 0,9, 0,4 y 3,7 respecto a BIB 88 y −1,8, −0,1 y 4,0 respecto a CAT 87, en las mujeres. Los valores del IMC de 25 y 30 “en la edad adulta” corresponden a los percentiles 80 y 97 en los varones y 85 y 97 en las mujeres.
En ambos sexos los valores de la talla media adulta son similares a los observados en otros estudios longitudinales y transversales españoles recientes y a los observados en estudios europeos y americanos, aunque inferiores a los de la población alemana, sueca y holandesa.
Con relación a estudios españoles previos, existe una aceleración secular de peso y talla, con un incremento desproporcionado en los valores del IMC correspondientes al percentil 75 o superiores, y de forma marcada en los del percentil 97. Este estudio muestra la necesidad de actualizar periódicamente los datos de referencia utilizados en la valoración del crecimiento durante la infancia y adolescencia.
In developed countries a secular trend in growth has been reported. Our aim was to evaluate weight, height and body mass index (BMI) values in a Spanish population coming from Andalusia, Barcelona, Bilbao and Zaragoza, and to compare these values with those obtained before 1988 (BIB 88 and CAT 87 studies).
Cross-sectional evaluation of height, weight and BMI in 32,064 subjects (16,607 males and 15,457 females) from birth to adulthood between the years 2000 and 2004. Three subpopulations were evaluated: a) 5,796 (2,974 males, 2,822 females) newborns at term from normal gestations; b) 23,701 (12,358 males; 11,343 females) children and adolescents 0.25-18 years old, and c) 2,567 (1,275 males, 1,292 females) young adults 18.1-24 years of age. All were healthy caucasians, and their parents from Spanish origin. The LSM method was used.
Mean, standard deviation, Skewness index and percentiles values with a 0.25-0.5 year-period intervals from birth to adulthood are reported. As regards the data obtained previously in Spanish populations, an increase of 1.8 cm, 1.4 cm and 3.3 cm were observed in adult height for percetiles 3, 50 and 97 in males respect to BIB 88 and 2.5 cm, 3.3 cm and 3.8 respect to CAT 87. In females these values were 3.5 cm, 2.5 cm and 4.2 cm respect to BIB 88 and 3.5 cm, 3.1 cm and 3.9 cm respect to CAT 87. The corresponding values for weight, in males, were increased in 5.4 kg, 6.2 kg and 11.7 kg respect to BIB 88 and 6.7 kg, 6.3 kg and 10.1 kg respect to CAT 87; in females these increased were 1.7 kg, 2,2 kg and 8.3 kg respect to BIB 88 and 1.8 kg, 2.4 kg and 3.6 kg respect to CAT 87. The corresponding increased for BMI values, in males, were 2.0, 1.4 and 3.9 respect to BIB 88 and −0.1, −0.2 and 5.3 respect to CAT 87; in females these values were 0.9, 0.4 and 3.7 respect to BIB 88 and −1.8, −0.1 and 4 respect to CAT 87. In young adults, 25 and 30 BMI values correspond to percentiles 80 and 97 in males, and 85 and 97 in females.
Mean values of adult height were similar to those observed in other longitudinal and cross-sectional Spanish, European, and American studies, but lower than those reported for German, Swedish and Netherlands populations.
A secular trend of growth was observed in our population with a non-proportional increased of weight to height ratio (BMI) values, particularly for those corresponding to the 97 percentile. The need of periodical updates of growth data used in the evaluation of children and adolescents is required.
PDF
