Dark Ages Cold Period: A literature review and directions for future research

Several late Quaternary studies have recorded cold and disturbed climates centred during the mid-first millennium AD and discussed these conditions under the term ‘Dark Ages Cold Period’ (DACP). A review of 114 palaeoclimate papers indicated that cold climates were common in the Northern Hemisphere between AD 400 and 765. There are also suggestions that some regions may have been relatively wet during the DACP, while those around the Mediterranean and the China/Tibetan Plateau indicate coinciding droughts. A set of environmental responses, however, indicate a delayed DACP interval (AD 509–865) postdating the actual climate signal. Previously, the DACP has been linked with the North Atlantic ice-rafting event at about 1400 years ago, while some evidence suggests an involvement of the North Atlantic Oscillation and/or El Niño–Southern Oscillation. More recently, another proposed phase of widespread cooling, the ‘Late Antique Little Ice Age’ (LALIA), overlaps with the DACP and has been tentatively linked with volcanic aerosol and solar irradiance variations reinforcing the climatic downturn since AD 536. Importantly, a higher number of proxy records extending over the first millennium AD is required for more rigorous assessments of climate variability and the forcing during these centuries and to disentangle the DACP and LALIA fingerprints in the proxy data, particularly to determine whether the DACP and the LALIA are distinct features. Also a richer network of both climate and environmental proxies is needed to evaluate the human–environment interactions, during the historical Migration Period, and thus through the DACP

Tropomyosin receptor kinase inhibitors in the management of sarcomas.

Purpose of review Genetic aberrations resulting in tropomyosin receptor kinase (TRK) fusion proteins can drive oncogenesis and are postulated to occur in up to 1% of solid tumours. However, TRK fusions in adult sarcomas are rare and there is a significant challenge in identifying patients with sarcomas harbouring TRK fusions in the clinical setting. Despite a recent European Society of Medical Oncology consensus article regarding screening of tumours for TRK fusions, economical and practical limitations present a barrier to widespread screening of sarcomas.Recent findings Larotrectinib and entrectinib are pan-TRK inhibitors which have both received FDA approval for the management of solid tumours harbouring NTRK fusions. Initial results of a number of clinical trials have demonstrated promising efficacy and safety data, including dramatic and durable responses in patients with sarcomas. As such, TRK inhibitors represent a promising treatment option in a small cohort of adult sarcoma patients, where currently treatment options are limited. The emergence of acquired resistance is a concern associated with TRK inhibitor therapy and a number of second-generation agents targeting TRK kinase mutations driving acquired resistance have entered early-phase clinical trials.Summary With the growing appreciation of the implications of TRK fusions, this review will summarize the emerging clinical trial data of TRK inhibitors in sarcomas. Although in their infancy, clinical trial results are encouraging, and as further results and analyses are released, we will have a greater understanding of their impact on clinical practice and the management of patients with sarcomas

Suppression of Cross-Band Scattering in Multiband Antenna Arrays

© 1963-2012 IEEE. This paper presents a novel method of suppressing cross-band scattering in dual-band dual-polarized antenna arrays. The method involves introducing chokes into low-band (LB) elements to suppress high-band (HB) scattering currents. The experimental results show that by inserting LB-pass HB-stop chokes into LB radiators, suppression of induced HB currents on the LB elements is achieved. This greatly reduces the pattern distortion of the HB array caused by the presence of LB elements. The array considered is configured as two columns of HB antennas operating from 1.71 to 2.28 GHz interleaved with a single column of LB antennas operating from 0.82 to 1.0 GHz. The realized array with choked LB element has stable and symmetrical radiation in both HB and LB

Effects of acute exercise on cutaneous thermal sensation

The aim of this study was to assess the effect of exercise intensity on thermal sensory function of active and inactive limbs. In a randomised and counterbalanced manner 13 healthy young male participants (25±6 yr, 1.8±0.1 m, 77±6 kg) conducted; 1) 30 minutes low (50% heart rate maximum, HRmax; LOW) intensity, 2) 30 minutes high (80% HRmax; HIGH) intensity cycling exercise and 3) 30 minutes seated rest (CONTROL). Before, immediately and 1-hour after each intervention thermal sensory function of the non-dominant dorsal forearm and posterior calf were examined by increasing local skin temperature (1°C/s) to assess perceptual heat sensitivity and pain thresholds. Relative to pre-exercise, forearm heat sensitivity thresholds were increased immediately and 1-hr after HIGH but there were no changes after LOW exercise or during CONTROL (main effect of trial; P=0.017). Relative to pre-exercise, calf heat sensitivity thresholds were not changed after LOW or HIGH exercise or during CONTROL (main effect of trial; P=0.629). There were no changes in calf (main effect of trial; P=0.528) or forearm (main effect of trial; P=0.088) heat pain thresholds after exercise in either LOW or HIGH or CONTROL. These results suggest that cutaneous thermal sensitivity function of an inactive limb is only reduced after higher intensity exercise but is not changed in a previously active limb after exercise. Exercise does not affect heat pain sensitivity in either active or inactive limbs

Exploring the measurement of markedness and its relationship with other linguistic variables

Antonym pair members can be differentiated by each word's markedness-that distinction attributable to the presence or absence of features at morphological or semantic levels. Morphologically marked words incorporate their unmarked counterpart with additional morphs (e.g., "unlucky" vs. "lucky"); properties used to determine semantically marked words (e.g., "short" vs. "long") are less clearly defined. Despite extensive theoretical scrutiny, the lexical properties of markedness have received scant empirical study. The current paper employs an antonym sequencing approach to measure markedness: establishing markedness probabilities for individual words and evaluating their relationship with other lexical properties (e.g., length, frequency, valence). Regression analyses reveal that markedness probability is, as predicted, related to affixation and also strongly related to valence. Our results support the suggestion that antonym sequence is reflected in discourse, and further analysis demonstrates that markedness probabilities, derived from the antonym sequencing task, reflect the ordering of antonyms within natural language. In line with the Pollyanna Hypothesis, we argue that markedness is closely related to valence; language users demonstrate a tendency to present words evaluated positively ahead of those evaluated negatively if given the choice. Future research should consider the relationship of markedness and valence, and the influence of contextual information in determining which member of an antonym pair is marked or unmarked within discourse

Suppression of Cross-Band Scattering in Interleaved Dual-Band Cellular Base-Station Antenna Arrays

© 2013 IEEE. In this article, novel techniques to suppress cross-band scattering in interleaved dual-band base station antenna arrays are presented. Firstly, the detrimental effect of high-band (HB) elements on low-band (LB) radiation performance is theoretically analyzed. With a thorough analysis, a capacitance-loaded HB element is innovated to solve the issue and restore the LB patterns. Secondly, to eliminate the reverse HB scattering caused by the LB element while enhancing the bandwidth of the LB element, a novel double-arm choked cross-dipole configuration is proposed. A compact array section is built with these innovated elements. The experimental results of the array show a largely suppressed cross-band scattering with stable radiation performance across the well-matched bands, demonstrating the effectiveness of the presented techniques

Wind Data Mining by Kohonen Neural Networks

Time series of Circulation Weather Type (CWT), including daily averaged wind direction and vorticity, are self-classified by similarity using Kohonen Neural Networks (KNN). It is shown that KNN is able to map by similarity all 7300 five-day CWT sequences during the period of 1975–94, in London, United Kingdom. It gives, as a first result, the most probable wind sequences preceding each one of the 27 CWT Lamb classes in that period. Inversely, as a second result, the observed diffuse correlation between both five-day CWT sequences and the CWT of the 6(th) day, in the long 20-year period, can be generalized to predict the last from the previous CWT sequence in a different test period, like 1995, as both time series are similar. Although the average prediction error is comparable to that obtained by forecasting standard methods, the KNN approach gives complementary results, as they depend only on an objective classification of observed CWT data, without any model assumption. The 27 CWT of the Lamb Catalogue were coded with binary three-dimensional vectors, pointing to faces, edges and vertex of a “wind-cube,” so that similar CWT vectors were close

Computer-Aided Design and Analysis of Spectrally Aligned Hybrid Plasmonic Nanojunctions for SERS Detection of Nucleobases

Hybrid plasmonic nanojunctions with optimal surface-enhanced Raman scattering (SERS) activity are designed via a computer-aided approach, and fabricated via time-controlled aqueous self-assembly of core@shell gold@silver nanoparticles (Au@Ag NPs) with cucurbit[7]uril (CB7) upon simple mixing. The authors showed that SERS signals can be significantly boosted by the incorporation of a strong plasmonic metal and the spectral alignment between the maximal localized surface plasmon resonance (LSPR) and a laser wavelength used for SERS excitation. In a proof-of-concept application, SERS detection of nucleobases with a 633-nm laser has been demonstrated by positioning them within the nanojunctions via formation of host–guest complexes with CB7, achieving rapid response with a detection limit down to sub-nanomolar concentration and an enhancement factor (EF) up to ≈109–1010, i.e., the minimum required EF for single-molecule detection. Furthermore, machine-learning-driven multiplexing of nucleobases is demonstrated, which shows promise in point-of-care diagnosis of diseases related to oxidative damage of DNA and wastewater-based epidemiology

Reconstruction of Lamb weather type series back to the eighteenth century

The Lamb weather type series is a subjective catalogue of daily atmospheric patterns and flow directions over the British Isles, covering the period 1861–1996. Based on synoptic maps, meteorologists have empirically classified surface pressure patterns over this area, which is a key area for the progression of Atlantic storm tracks towards Europe. We apply this classification to a set of daily pressure series from a few stations from western Europe, in order to reconstruct and to extend this daily weather type series back to 1781. We describe a statistical framework which provides, for each day, the weather types consistent enough with the observed pressure pattern, and their respective probability. Overall, this technique can correctly reconstruct almost 75% of the Lamb daily types, when simplified to the seven main weather types. The weather type series are described and compared to the original series for the winter season only. Since the low frequency variability of synoptic conditions is directly related to the North Atlantic Oscillation (NAO), we derive from the weather type series an NAO index for winter. An interesting feature is a larger multidecadal variability during the nineteenth century than during the twentieth century

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m(2)) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects