IBD confers an increased lifetime risk of developing colorectal cancer (CRC), and colitis-associated CRC (CA-CRC) is molecularly distinct from sporadic CRC (S-CRC). Here we have dissected the ...evolutionary history of CA-CRC using multiregion sequencing.
Exome sequencing was performed on fresh-frozen multiple regions of carcinoma, adjacent non-cancerous mucosa and blood from 12 patients with CA-CRC (n=55 exomes), and key variants were validated with orthogonal methods. Genome-wide copy number profiling was performed using single nucleotide polymorphism arrays and low-pass whole genome sequencing on archival non-dysplastic mucosa (n=9), low-grade dysplasia (LGD; n=30), high-grade dysplasia (HGD; n=13), mixed LGD/HGD (n=7) and CA-CRC (n=19). Phylogenetic trees were reconstructed, and evolutionary analysis used to reveal the temporal sequence of events leading to CA-CRC.
10/12 tumours were microsatellite stable with a median mutation burden of 3.0 single nucleotide alterations (SNA) per Mb, ~20% higher than S-CRC (2.5 SNAs/Mb), and consistent with elevated ageing-associated mutational processes. Non-dysplastic mucosa had considerable mutation burden (median 47 SNAs), including mutations shared with the neighbouring CA-CRC, indicating a precancer mutational field. CA-CRCs were often near triploid (40%) or near tetraploid (20%) and phylogenetic analysis revealed that copy number alterations (CNAs) began to accrue in non-dysplastic bowel, but the LGD/HGD transition often involved a punctuated 'catastrophic' CNA increase.
Evolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD. Detection of the cancerised field is an encouraging prospect for surveillance, but punctuated evolution may limit the window for early detection.
This study documents the global distribution and characteristics of diurnally varying low-level jets (LLJs), including their horizontal, vertical, and temporal structure, with a special emphasis on ...highlighting the underlying commonalities and unique qualities of the various nocturnal jets. Two tools are developed to accomplish this goal. The first is a 21-yr global reanalysis performed with the fifth-generation Pennsylvania State University–NCAR Mesoscale Model (MM5) using a horizontal grid spacing of 40 km. A unique characteristic of the reanalysis is the availability of hourly three-dimensional output, which permits the full diurnal cycle to be analyzed. Furthermore, the horizontal grid spacing of 40 km better resolves many physiographic features that host LLJs than other widely used global reanalyses. This makes possible a detailed examination of the systematic onset and cessation of the jets, including time–height representations of the diurnal cycle. The second tool is an index of nocturnal LLJ (NLLJ) activity based upon the vertical structure of the wind’s temporal variation, where the temporal variation is defined in local time. The first available objectively constructed global maps of recurring NLLJs are created from this index, where the various NLLJs can be simultaneously viewed at or near their peak time. These maps not only highlight all of the locations where NLLJs are known to recur, but they also reveal a number of new jets.
The authors examine the basic mechanisms that give rise to the NLLJs identified in four disparate locations, each having a profound influence on the regional climate. The first, the extensively studied Great Plains NLLJ, is used to confirm the veracity of the global analysis and the index of NLLJ activity. It also provides context for three of the many newly identified NLLJs: 1) Tarim Pendi in northwest China; 2) Ethiopia in eastern Africa; and 3) Namibia–Angola in southwest Africa. Jets in these four regions illustrate the variety of physiographic and thermal forcing mechanisms that can produce NLLJs.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PURPOSE:To determine the effect of steep Trendelenburg (sTBURG) surgical positioning on intraocular pressure (IOP) during robotic-assisted laparoscopy (RAL) in subjects without previously identified ...ocular disease.
DESIGN:Prospective cohort study.
PARTICIPANTS AND CONTROLS:Eighteen patients undergoing RAL with sTBURG and 21 controls undergoing open and laparoscopic cases in horizontal positioning.
MATERIALS AND METHODS:Research data derived from an approved Naval Medical Center, San Diego, CA, IRB protocol. A study group undergoing RAL utilizing sTBURG (group 1) was compared with a control group undergoing open surgery in the horizontal position (group 2), and laparoscopic cases in the horizontal position (group 3). An ophthalmologic examination including Snellen visual acuity, IOP, Humphrey Visual Field (HVF) 24-2 with standard Swedish Interactive Thresholding Algorithm, time domain optical coherence tomography (OCT), retinal nerve fiber layer (RNFL) analysis, pachymetry, and dilated fundus examination was conducted preoperatively and at 1 month postoperatively. IOP was measured intraoperatively at discrete time-points.
MAIN OUTCOME MEASURES:IOP values, change in OCT RNFL thickness, HVF mean deviation, and HVF pattern standard deviation.
RESULTS:Baseline IOP (mm Hg) was similar, 13.7±3.2 for group 1 versus 15.3±3.2 for group 2 and 14.1±2.4 for group 3 (P=0.55). The IOP plateau from 60 minutes until case conclusion occurred at 29.9 mm Hg (95% confidence interval, 27.4-32.5), 19.9 mm Hg (95% confidence interval, 17.6-22.3), and 22.8 mm Hg (95% confidence interval, 20.2-25.4) for group 1, group 2, and group 3, respectively. There were no significant changes in OCT RNFL thickness, HVF mean deviation, and HVF pattern standard deviation.
CONCLUSIONS:Significant elevations of IOP are experienced during robotic surgery utilizing sTBURG positioning in patients with healthy eyes, and we recommend a multidisciplinary approach in determining potential risk to those with known ocular disease who are candidates for these procedures.
Background. In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal β-lactams for methicillin-resistant Staphylococcus aureus ...(MRSA) bacteremia. Prospective clinical data are lacking. Methods. In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. Results. We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%–102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. Conclusions. Combining an antistaphylococcal β-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).
Obesity is a chronic disease that disproportionately affects individuals from nonmajority racial/ethnic groups in the United States. Research shows that individuals from minority racial/ethnic ...backgrounds consider it important to have access to providers from diverse backgrounds. Health care providers and scientists from minority racial/ethnic groups are more likely than non-Hispanic whites to treat or conduct research on patients from underrepresented groups.
To characterize the racial/ethnic diversity of nutrition- and obesity-focused professional organizations in the United States.
This study assessed race/ethnicity data from several obesity-focused national organizations including The Obesity Society, the Academy of Nutrition and Dietetics (AND), the American Society for Nutrition, and the American Board of Obesity Medicine (ABOM). Each organization was queried via emailed survey to provide data on racial/ethnic representation among their membership in the past 5 y and among elected presidents from 2010 to 2020.
Two of the 3 professional societies queried did not systematically track race/ethnicity data at the time of query. Limited tracking data available from AND show underrepresentation of black (2.6%), Asian (3.9%), Latinx (3.1%), Native Hawaiian or Pacific Islander: (1.3%), or indigenous (American Indian or Alaskan Native: 0.3%) individuals compared with the US population. Underrepresentation of racial/ethnic minorities was also reported for ABOM diplomates (black: 6.0%, Latinx: 5.0%, Native American: 0.2%). Only AND reported having racial/ethnic diversity (20%) among the organization’s presidents within the previous decade (2010–2020).
Findings suggest that 1) standardized tracking of race and ethnicity data is needed to fully assess diversity, equity, and inclusion, and 2) work is needed to increase the diversity of membership and leadership at the presidential level within obesity- and nutrition-focused professional organizations. A diverse cadre of obesity- and nutrition-focused health care professionals is needed to further improve nutrition-related health outcomes, including obesity, cardiovascular disease, diabetes, and undernutrition, in this country.
Purpose Active surveillance is an important alternative to definitive therapy for men with low risk prostate cancer. However, the impact of active surveillance on health related quality of life ...compared to that in men without cancer remains unknown. In this study we evaluated health related quality of life outcomes in men on active surveillance compared to men followed after negative prostate needle biopsy. Materials and Methods A prospective study was conducted on men who were enrolled into the CPDR Multicenter National Database and underwent prostate needle biopsy for suspicion of prostate cancer between 2007 and 2014. Health related quality of life was assessed at biopsy (baseline) and annually for up to 3 years using SF-36 and EPIC questionnaires. Health related quality of life scores were modeled using generalized estimating equations, adjusting for baseline health related quality of life, and demographic and clinical characteristics. Results Of the 1,204 men who met the initial eligibility criteria 420 had a negative prostate needle biopsy (noncancer comparison group). Among the 411 men diagnosed with low risk prostate cancer 89 were on active surveillance. Longitudinal analysis revealed that for most health related quality of life subscales there were no significant differences between the groups in adjusted health related quality of life score trends over time. Conclusions In this study most health related quality of life outcomes in patients with low risk prostate cancer on active surveillance did not differ significantly from those of men without prostate cancer. A comparison group of men with a similar risk of prostate cancer detection is critical to clarify the psychological and physical impact of active surveillance.
Objective
Obesity is a chronic disease that disproportionately affects individuals from nonmajority racial/ethnic groups in the United States. Research shows that individuals from minority ...racial/ethnic backgrounds consider it important to have access to providers from diverse backgrounds. Health care providers and scientists from minority racial/ethnic groups are more likely than their non‐Hispanic White counterparts to treat or conduct research on patients from underrepresented groups. The objective of this study was to characterize the racial/ethnic diversity of nutrition‐ and obesity‐focused professional organizations in the United States.
Methods
This study assessed race/ethnicity data from several obesity‐focused national organizations including The Obesity Society, the Academy of Nutrition and Dietetics (AND), the American Society for Nutrition, and the American Board of Obesity Medicine (ABOM). Each organization was queried via emailed survey to provide data on racial/ethnic representation among their membership in the past 5 years and among elected presidents from 2010 to 2020.
Results
Two of the three professional societies queried did not systematically track race/ethnicity data at the time of query. Limited tracking data available from AND show underrepresentation of Black (2.6%), Asian (3.9%), Latinx (3.1%), Native Hawaiian or Pacific Islander (1.3%), or indigenous (American Indian or Alaskan Native: 0.3%) individuals compared with the US population. Underrepresentation of racial/ethnic minorities was also reported for ABOM diplomates (Black: 6.0%, Latinx: 5.0%, Native American: 0.2%). Only AND reported having racial/ethnic diversity (20%) among the organization’s presidents within the previous decade (2010–2020).
Conclusions
Findings suggest that (1) standardized tracking of race and ethnicity data is needed to fully assess diversity, equity, and inclusion, and (2) work is needed to increase the diversity of membership and leadership at the presidential level within obesity‐ and nutrition‐focused professional organizations. A diverse cadre of obesity‐ and nutrition‐focused health care professionals is needed to further improve nutrition‐related health outcomes, including obesity, cardiovascular disease, diabetes, and undernutrition, in this country.
Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, ...whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumours. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal centre B cells ('germinal centre B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal centre B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumours on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Empiric antibiotic therapy in suspected prosthetic joint infection should cover likely pathogens while avoiding overly broad‐spectrum antibiotics. We analysed individual patient data from a large ...prospective cohort study (Prosthetic Joint Infection in Australia and New Zealand, Observational (PIANO)) and found that causative organisms vary with the presentation type, with early post‐operative infections more likely to be polymicrobial (41%) compared with late acute infections (10%). We thus propose empirical regimens tailored to the presentation type and presence or absence of sepsis.
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