The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing ...adjunct host-directed therapies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
Pathological complete response (pCR) to neoadjuvant treatment correlates with outcome in breast cancer. We determined whether characteristics of neoadjuvant therapy are associated with pCR. We used ...multi-level models, which accounted for heterogeneity in pCR across trials and trial arms, to analyze individual patient data from 3332 women included in 7 German neoadjuvant trials with uniform protocols. PCR was associated with an increase in number of chemotherapy cycles (odds ratio OR 1.2 for every two additional cycles; P = 0.009), with higher cumulative anthracycline doses (OR 1.6; P = 0.002), higher cumulative taxane doses (OR 1.6; P = 0.009), and with capecitabine containing regimens (OR 1.62; P = 0.022). Association of pCR with increase in number of cycles appeared more pronounced in hormone receptor (HR)-positive tumors (OR 1.35) than in HR-negative tumors (OR 1.04; P for interaction = 0.046). Effect of anthracycline dose was particularly pronounced in HER2-negative tumors (OR 1.61), compared to HER2-positive tumors (OR 0.83; P for interaction = 0.14). Simultaneous trastuzumab treatment in HER2-positive tumors increased odds of pCR 3.2-fold (P < 0.001). No association of pCR and number of trastuzumab cycles was found (OR 1.20, P = 0.39). Dosing characteristics appear important for successful treatment of breast cancer. Longer treatment, higher cumulative doses of anthracyclines and taxanes, and the addition of capecitabine and trastuzumab are associated with better response. Tailoring according to breast cancer phenotype might be possible: longer treatment in HR-positive tumors, higher cumulative anthracycline doses for HER2-negative tumors, shorter treatment at higher cumulative doses for triple-negative tumors, and limited number of preoperative trastuzumab cycles in HER2-positive tumors.
Sensors are a major component in any experimental set-up. In a high voltage environment, the aspect of safety must be particularly emphasized and the galvanic isolation is often provided by an ...optical communication link in between the "electric-sensor" and the "detection-unit". However, the transformation of electrical to optical signals and back can introduce delays and errors. To mitigate this, electric fields were directly measured with an in-house fabricated optical sensor chip, based on lithium niobate. On the one hand we measured locally with electrodes on chip, on the other hand in an external electric field across the sensor. Here, we measured a sensitivity of <inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>(8 mV)/(10 kV/cm) on the chip with peak ac field strengths up to 11 kV/cm and <inline-formula> <tex-math notation="LaTeX">\sim </tex-math></inline-formula>(10 mV)/(1 kV/cm) in free space for 2 kV/cm at net frequency of 50 Hz. Hysteresis effects on the sensor were found to be decreased for the free space arrangement. Thus, the fabrication and test procedures work effectively and the electric field measurements showed a good agreement of the performance comparing the on-chip and free space set up. This allows for fast and easy on-chip testing of new resonator based sensors to optimize the geometry and adapt the sensor to its application.
For a durable improvement of the hydrophobization properties of wood Scots pine (
L.) sapwood veneer chips were covalently modified with surfactant-like
-alkylated benzoates and a corresponding ...4-cyanophenyl derivative. These esterification reactions of wood hydroxyl groups at varied temperatures and different reaction times afforded weight percent gains (WPG) ranging from 8 to 44% and quantities of covalently bonded organomaterials (QCO) of 0.3–2.6 mmol per gram, respectively. The successful covalent attachment of the functional precursors was proven by attenuated total reflection-infrared spectroscopy (ATR-IR), while the improvement of hydrophobicity was demonstrated by resulting contact angles (CAs) in a range from 113 to 150°.
Helical locking of spin and momentum and prohibited backscattering are the key properties of topologically protected states. They are expected to enable novel types of information processing by ...providing pure spin currents, or fault tolerant quantum computation by using the Majorana fermions at interfaces of topological states with superconductors. So far, the required helical conduction channels used to realize Majorana fermions are generated through the application of an axial magnetic field to conventional semiconductor nanowires. Avoiding the magnetic field enhances the possibilities for circuit design significantly. Here, we show that subnanometre-wide electron channels with natural helicity are present at surface step edges of the weak topological insulator Bi14 Rh3 I9 (ref. ). Scanning tunneling spectroscopy reveals the electron channels to be continuous in both energy and space within a large bandgap of 200 meV, evidencing its non-trivial topology. The absence of these channels in the closely related, but topologically trivial compound Bi13 Pt3 I7 corroborates the channels' topological nature. The backscatter-free electron channels are a direct consequence of Bi14 Rh3 I9 's structure: a stack of two-dimensional topologically insulating, graphene-like planes separated by trivial insulators. We demonstrate that the surface of Bi14 Rh3 I9 can be engraved using an atomic force microscope, allowing networks of protected channels to be patterned with nanometre precision.
The role of autologous-allogeneic tandem stem cell transplantation (alloTSCT) followed by maintenance as upfront treatment for multiple myeloma is controversial. Between 2008 and 2014 a total of 217 ...multiple myeloma patients with a median age of 51 years were included by 20 German centers within an open-label, parallel-group, multicenter clinical trial to compare alloTSCT to autologous tandem transplantation (autoTSCT) followed by 2 years of maintenance therapy with thalidomide (100 mg/day) in both arms with respect to relapse/progression-free survival (PFS) and other relevant outcomes. A total of 178 patients underwent a second transplant (132 allogeneic, 46 autologous). PFS at 4 years after the second transplant was 47% (95% CI: 38-55%) for alloTSCT and 35% (95% CI: 21-49%) for autoTSCT (P=0.26). This difference increased to 22% at 8 years (P=0.10). The cumulative incidences of non-relapse mortality and of relapse at 4 years were 13% (95% CI: 8-20%) and 2% (95% CI: 0.3-2%) (P=0.044) and 40% (95% CI: 33-50%) and 63% (95% CI: 50-79%) (P=0.04) for alloTSCT and autoTSCT, respectively. The difference for relapse/progression increased to 33% (alloTSCT: 44%, autoTSCT: 77%) at a median follow-up of 82 months (P=0.002). Four-year overall survival was 66% (95% CI: 57-73%) for alloTSCT and 66% (95% CI: 50-78%) for autoTSCT (P=0.91) and 8-year overall survival was 52% and 50% (P=0.87), respectively. In conclusion, alloTSCT followed by thalidomide maintenance reduced the rate of recurrence or progression during a follow-up period of up to 10 years but failed to improve PFS significantly. This study was registered with ClinicalTrials.gov (NCT00777998).
Objective
To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from ...intracranial electroencephalographic (iEEG) recordings.
Methods
Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006‐2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports.
Results
In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic‐clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS‐BTCs; 556/654, P < .001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P = .003) and was significantly shortened (P < .001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P = .015) and sign of four (P = .043) were associated with longer bilateral tonic‐clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P < .001) and disease duration (P = .028) were essential for prediction of FS‐BTC duration, whereas the vigilance state (P = .085) was the main prediction factor for the duration of FBTCSs.
Significance
The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.
For the design of thick-walled cast iron components used for wind energy turbines, large machines, presses, and engine parts made of nodular cast iron, the assessment of fatigue life of critical ...component areas is a crucial point to consider. Importance increases with the demand to safe resources by applying a lightweight design in combination with a certain resistance against extreme loads and misuse situations. Moreover, this gets more important when notches or deviations in the local microstructure are present. Nevertheless, due to accessibility, a lack in the description of the local strain-based material behavior still exists. Especially new cast iron grades such as ADI are not well investigated but offer an often-discussed potential for a lightweight design of the structure or to increase the highest admissible load on the structure. To determine the cyclic material behavior of nodular cast iron, different grades EN-GJS-400-18LT, EN-GJS-450-18, EN-GJS-500-14, EN-GJS-600-3, EN-GJS-700-2, and ADI in different wall thicknesses were investigated concerning their elastic–plastic material behavior under strain control. Moreover, new possibilities for the trilinear description of the strain-life and the stress–strain curve and the statistical and technological size effect are discussed in the following based on cyclic stress–strain and strain-life curves.
In people with human immunodeficiency virus (HIV) (PWH), individual polygenic risk scores (PRSs) are associated with coronary artery disease (CAD) events. Whether PRSs are associated with subclinical ...CAD is unknown.
In Swiss HIV Cohort Study participants of European descent, we defined subclinical CAD as presence of soft, mixed, or high-risk plaque (SMHRP) on coronary computed tomography (CT) angiography, or as participants in the top tertile of the study population's coronary artery calcium (CAC) score, using noncontrast CT. We obtained univariable and multivariable odds ratios (ORs) for subclinical CAD endpoints based on nongenetic risk factors, and validated genome-wide PRSs built from single nucleotide polymorphisms associated with CAD, carotid intima-media thickness (IMT), or longevity in the general population.
We included 345 genotyped participants (median age, 53 years; 89% male; 96% suppressed HIV RNA); 172 and 127 participants had SMHRP and CAC, respectively. CAD-associated PRS and IMT-associated PRS were associated with SMHRP and CAC (all P < .01), but longevity PRS was not. Participants with unfavorable CAD-PRS (top quintile) had an adjusted SMHRP OR = 2.58 (95% confidence interval CI, 1.18-5.67), and a CAC OR = 3.95 (95% CI, 1.45-10.77) vs. bottom quintile. Unfavorable nongenetic risk (top vs. bottom quintile) was associated with adjusted SMHRP OR = 24.01 (95% CI, 9.75-59.11), and a CAC-OR = 65.07 (95% CI, 18.48-229.15). Area under the receiver operating characteristic curve increased when we added CAD-PRS to nongenetic risk factors (SMHRP: 0.75 and 0.78, respectively; CAC: 0.80 and 0.83, respectively).
In Swiss PWH, subclinical CAD is independently associated with an individual CAD-associated PRS. Combining nongenetic and genetic cardiovascular risk factors provided the most powerful subclinical CAD prediction.
Summary Reduction of active disease by preventive therapy has the potential to make an important contribution towards the goal of tuberculosis (TB) elimination. This report summarises discussions ...amongst a Working Group convened to consider areas of research that will be important in optimising the design and delivery of preventative therapies. The Working Group met in Cape Town on 26th February 2012, following presentation of results from the GC11 Grand Challenges in Global Health project to discover drugs for latent TB.
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