We observed robust coupling between the high- and low-frequency bands of ongoing electrical activity in the human brain. In particular, the phase of the low-frequency theta (4 to 8 hertz) rhythm ...modulates power in the high gamma (80 to 150 hertz) band of the electrocorticogram, with stronger modulation occurring at higher theta amplitudes. Furthermore, different behavioral tasks evoke distinct patterns of theta/high gamma coupling across the cortex. The results indicate that transient coupling between low- and high-frequency brain rhythms coordinates activity in distributed cortical areas, providing a mechanism for effective communication during cognitive processing in humans.
The foot of Homo naledi Harcourt-Smith, W E H; Throckmorton, Z; Congdon, K A ...
Nature communications,
10/2015, Letnik:
6, Številka:
1
Journal Article
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Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated ...remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having more curved proximal pedal phalanges, and features suggestive of a reduced medial longitudinal arch. Within the context of primitive features found elsewhere in the skeleton, these findings suggest a unique locomotor repertoire for H. naledi, thus providing further evidence of locomotor diversity within both the hominin clade and the genus Homo.
Abstract Background Little is known about patterns of medication use and lifestyle counseling in patients with peripheral artery disease (PAD) in the United States. Objectives The authors sought to ...evaluate trends in both medical therapy and lifestyle counseling for PAD patients in the United States from 2005 through 2012. Methods Data from 1,982 outpatient visits among patients with PAD were obtained from the National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, a nationally representative assessment of office-based and hospital outpatient department practice. Trends in the proportion of visits with medication use (antiplatelet therapy, statins, angiotensin-converting enzyme inhibitors ACEIs or angiotensin receptor blockers ARBs, and cilostazol) and lifestyle counseling (exercise or diet counseling and smoking cessation) were evaluated. Results Over the 8-year period, the average annual number of ambulatory visits in the United States for PAD was 3,883,665. Across all visits, mean age was 69.2 years, 51.8% were female, and 56.6% were non-Hispanic white. Comorbid coronary artery disease (CAD) was present in 24.3% of visits. Medication use for cardiovascular prevention and symptoms of claudication was low: any antiplatelet therapy in 35.7% (standard error SE: 2.7%), statin in 33.1% (SE: 2.4%), ACEI/ARB in 28.4% (SE: 2.0%), and cilostazol in 4.7% (SE: 1.0%) of visits. Exercise or diet counseling was used in 22% (SE: 2.3%) of visits. Among current smokers with PAD, smoking cessation counseling or medication was used in 35.8% (SE: 4.6%) of visits. There was no significant change in medication use or lifestyle counseling over time. Compared with visits for patients with PAD alone, comorbid PAD and CAD were more likely to be prescribed antiplatelet therapy (odds ratio OR: 2.6; 95% confidence interval CI: 1.8 to 3.9), statins (OR: 2.6; 95% CI: 1.8 to 3.9), ACEI/ARB (OR: 2.6; 95% CI: 1.8 to 3.9), and smoking cessation counseling (OR: 4.4; 95% CI: 2.0 to 9.6). Conclusions The use of guideline-recommended therapies in patients with PAD was much lower than expected, which highlights an opportunity to improve the quality of care in these high-risk patients.
Glioblastoma multiforme (GBM) and single brain metastasis (MET) are the 2 most common malignant brain tumors that can appear similar on anatomic imaging but require vastly different treatment ...strategy. The purpose of our study was to determine whether the peak height and the percentage of signal intensity recovery derived from dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion MR imaging could differentiate GBM and MET.
Forty-three patients with histopathologic diagnosis of GBM (n=27) or MET (n=16) underwent DSC perfusion MR imaging in addition to anatomic MR imaging before surgery. Regions of interest were drawn around the nonenhancing peritumoral T2 lesion (PTL) and the contrast-enhancing lesion (CEL). T2* signal intensity-time curves acquired during the first pass of gadolinium contrast material were converted to the changes in relaxation rate to yield T2* relaxivity (Delta R2*) curve. The peak height of maximal signal intensity drop and the percentage of signal intensity recovery at the end of first pass were measured for each voxel in the PTL and CEL regions of the tumor.
The average peak height for the PTL was significantly higher (P=.04) in GBM than in MET. The average percentage of signal intensity recovery was significantly reduced in PTL (78.4% versus 82.8%; P=.02) and in CEL (62.5% versus 80.9%, P<.01) regions of MET compared with those regions in the GBM group.
The findings of our study show that the peak height and the percentage of signal intensity recovery derived from the Delta R2* curve of DSC perfusion MR imaging can differentiate GBM and MET.
The Canadian Hydrogen Intensity Mapping Experiment (CHIME) is a novel transit radio telescope operating across the 400-800 MHz band. CHIME is composed of four 20 m × 100 m semicylindrical paraboloid ...reflectors, each of which has 256 dual-polarization feeds suspended along its axis, giving it a 200 deg2 field of view. This, combined with wide bandwidth, high sensitivity, and a powerful correlator, makes CHIME an excellent instrument for the detection of fast radio bursts (FRBs). The CHIME Fast Radio Burst Project (CHIME/FRB) will search beam-formed, high time and frequency resolution data in real time for FRBs in the CHIME field of view. Here we describe the CHIME/FRB back end, including the real-time FRB search and detection software pipeline, as well as the planned offline analyses. We estimate a CHIME/FRB detection rate of 2-42 FRBs sky-1 day-1 normalizing to the rate estimated at 1.4 GHz by Vander Wiel et al. Likely science outcomes of CHIME/FRB are also discussed. CHIME/FRB is currently operational in a commissioning phase, with science operations expected to commence in the latter half of 2018.
Introduction There is epidemiological evidence that metal contaminants may play a role in the development of atherosclerosis and its complications. Moreover, a recent clinical trial of a metal ...chelator had a surprisingly positive result in reducing cardiovascular events in a secondary prevention population, strengthening the link between metal exposure and cardiovascular disease (CVD). This is, therefore, an opportune moment to review evidence that exposure to metal pollutants, such as arsenic, lead, cadmium, and mercury, is a significant risk factor for CVD. Methods We reviewed the English-speaking medical literature to assess and present the epidemiological evidence that 4 metals having no role in the human body (xenobiotic), mercury, lead, cadmium, and arsenic, have epidemiologic and mechanistic links to atherosclerosis and CVD. Moreover, we briefly review how the results of the Trial to Assess Chelation Therapy (TACT) strengthen the link between atherosclerosis and xenobiotic metal contamination in humans. Conclusions There is strong evidence that xenobiotic metal contamination is linked to atherosclerotic disease and is a modifiable risk factor.
Itch is a defining symptom of atopic dermatitis. Crosstalk between keratinocytes, the immune system and non‐histaminergic sensory nerves is responsible for the pathophysiology of chronic itch in ...atopic dermatitis. An expanding understanding of the contribution of the nervous system and its interaction with immune pathways in atopic itch are helping to identify new therapeutic strategies.
Talimogene laherparepvec (T‐VEC) is a modified herpes simplex virus, type 1 (HSV‐1), which can be administered intralesionally in patients with stage IIIB/C‐IVM1a unresectable melanoma (EMA label). ...The phase 3 OPTiM registration study showed an overall response rate (ORR) of 26%. Since December 2016, 48 eligible patients started treatment at the Netherlands Cancer Institute. We included 26 patients in this study with a follow up time ≥6 months, reporting Overall Response Rate (ORR), Disease Control Rate (DCR), Adverse Events (AE), prior treatment for melanoma and baseline characteristics, documented in a prospectively maintained database. In house developed treatment protocol consists of clinical evaluation, periodic PET‐CT and histological biopsies for response evaluation. Median follow‐up was 12.5 months. Of 26 patients, 16 (61.5%) had a Complete Response (CR) as their best response. Seven (26.9%) patients had a Partial Response (PR) as their best response, 1 (3.8%) patient Stable Disease (SD) and 2 (7.7%) patients Progressive Disease (PD). Best ORR was 88.5%. DCR was 92.3%. Grade 1–2 AEs occurred in all patients. Mostly, these consisted of fatigue, influenza‐like symptoms and injection site erythema. All patients underwent prior treatment. Prior treatment did not influence response or toxicity of T‐VEC. Best ORR for T‐VEC monotherapy at our institute was 88.5% with 61.5% achieving a CR. This prospective study for T‐VEC in early metastatic (stage IIIB/C‐IVM1a) melanoma demonstrated superior results to the phase 3 OPTiM study and confirms the role of oncolytic immunotherapy for melanoma.
What's new?
Talimogene laherparepvec (T‐VEC) is a modified herpes simplex virus, type 1 (HSV‐1), which is registered for the treatment of stage IIIB/C‐IVM1a unresectable locally advanced melanoma. Here the authors evaluated the response to this drug in 26 patients with a follow up longer than 6 months. They demonstrate promising response rates, with 61.5% of their treated patients achieving a CR. This indicates a strong potential of this novel drug in the rapidly developing field of immunotherapeutic treatment of melanoma.
Abstract Background Preoperative anemia is a well-established risk factor for short-term mortality in patients undergoing noncardiac surgery, but appropriate thresholds for transfusion remain ...uncertain. The objective of this study was to determine long-term outcomes associated with anemia, hemorrhage, and red blood cell transfusion in patients undergoing noncardiac surgery. Methods We performed a long-term follow-up study of consecutive subjects undergoing hip, knee, and spine surgery between November 1, 2008 and December 31, 2009. Clinical data were obtained from administrative and laboratory databases, and retrospective record review. Preoperative anemia was defined as baseline hemoglobin < 13 g/dL for men and < 12 g/dL for women. Hemorrhage was defined by International Classification of Diseases, Ninth Revision coding. Data on long-term survival were collected from the Social Security Death Index database. Logistic regression models were used to identify factors associated with long-term mortality. Results There were 3050 subjects who underwent orthopedic surgery. Preoperative anemia was present in 17.6% (537) of subjects, hemorrhage occurred in 33 (1%), and 766 (25%) received at least one red blood cell transfusion. Over 9015 patient-years of follow-up, 111 deaths occurred. Anemia (hazard ratio HR 3.91; confidence interval CI, 2.49-6.15) and hemorrhage (HR 5.28; 95% CI, 2.20-12.67) were independently associated with long-term mortality after multivariable adjustment. Red blood cell transfusion during the surgical hospitalization was associated with long-term mortality (HR 3.96; 95% CI, 2.47-6.34), which was attenuated by severity of anemia (no anemia HR 4.39, mild anemia HR 2.27, and moderate/severe anemia HR 0.81; P for trend .0015). Conclusions Preoperative anemia, perioperative bleeding, and red blood cell transfusion are associated with increased mortality at long-term follow-up after noncardiac surgery. Strategies to minimize anemia and bleeding should be considered for all patients, and restrictive transfusion strategies may be advisable. Further investigation into mechanisms of these adverse events is warranted.
BRAF V600E is the genetic lesion underlying hairy-cell leukemia. We assessed the safety and activity of the oral BRAF inhibitor vemurafenib in patients with hairy-cell leukemia that had relapsed ...after treatment with a purine analogue or who had disease that was refractory to purine analogues.
We conducted two phase 2, single-group, multicenter studies of vemurafenib (at a dose of 960 mg twice daily)--one in Italy and one in the United States. The therapy was administered for a median of 16 weeks in the Italian study and 18 weeks in the U.S. study. Primary end points were the complete response rate (in the Italian trial) and the overall response rate (in the U.S. trial). Enrollment was completed (28 patients) in the Italian trial in April 2013 and is still open (26 of 36 planned patients) in the U.S. trial.
The overall response rates were 96% (25 of 26 patients who could be evaluated) after a median of 8 weeks in the Italian study and 100% (24 of 24) after a median of 12 weeks in the U.S. study. The rates of complete response were 35% (9 of 26 patients) and 42% (10 of 24) in the two trials, respectively. In the Italian trial, after a median follow-up of 23 months, the median relapse-free survival was 19 months among patients with a complete response and 6 months among those with a partial response; the median treatment-free survival was 25 months and 18 months, respectively. In the U.S. trial, at 1 year, the progression-free survival rate was 73% and the overall survival rate was 91%. Drug-related adverse events were usually of grade 1 or 2, and the events most frequently leading to dose reductions were rash and arthralgia or arthritis. Secondary cutaneous tumors (treated with simple excision) developed in 7 of 50 patients. The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.
A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. (Funded by the Associazione Italiana per la Ricerca sul Cancro and others; EudraCT number, 2011-005487-13; ClinicalTrials.gov number NCT01711632.).
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