Individual Differences in Substance Use Motives, Trauma, and Stress Among College-Based Polysubstance Users.

Background: Co-use of alcohol and other drugs within a certain time frame (i.e., polysubstance use) has become increasingly prevalent, particularly among college-aged individuals, but understanding motives for co-use remains limited. Polysubstance use has been associated with a higher likelihood of negative health consequences as compared to single substance use. Objectives: The current study examined associations between motivations for using alcohol, tobacco, and cannabis among college students who use multiple substances versus students using only one substance or no substances. Additionally, we examined the effect of trauma and daily stress on polysubstance use in self-report data from individuals (N=134) participating in the MAPme Study. Results: First, the observed prevalence of polysubstance use was greater than expected by chance, with most individuals co-using alcohol and cannabis. "Alcohol and Other Drug Users" were more frequently motivated to drink for social (ß=0.27, CI=[0.07, 0.44]), enhancement (ß=0.26, CI=[0.01, 0.42]) and coping (ß=0.21, CI=[0.06, 0.47]) reasons compared to individuals who consumed alcohol alone. Conclusions: Individual differences in motivations for use were partly explained by frequency of alcohol use and alcohol problem severity, but not by history of trauma or stress. Finally, while patterns of correlations among motivations for use across substances suggested a general tendency to be motivated to use substances for similar reasons, this was not supported by confirmatory factor models. Overall, shared motives may inform potential behavioral patterns for co-use of substances during college and might advise future treatment efforts.

Emerging adults tend to use multiple substances, particularly alcohol and cannabisCorrelation patterns suggest shared motives within rather than across substancesAlcohol problem severity and alcohol frequency predict motives for use.

Why Taste Is Pharmacology.

The chapter presents an argument supporting the view that taste, defined as the receptor-mediated signaling of taste cells and consequent sensory events, is proper subject matter for the field of pharmacology. The argument develops through a consideration of how the field of pharmacology itself is to be defined. Though its application toward the discovery and development of therapeutics is of obvious value, pharmacology nevertheless is a basic science committed to examining biological phenomena controlled by the selective interactions between chemicals - regardless of their sources or uses - and receptors. The basic science of pharmacology is founded on the theory of receptor occupancy, detailed here in the context of taste. The discussion then will turn to consideration of the measurement of human taste and how well the results agree with the predictions of receptor theory.

A Pharmacological Perspective on the Study of Taste.

The study of taste has been guided throughout much of its history by the conceptual framework of psychophysics, where the focus was on quantification of the subjective experience of the taste sensations. By the mid-20th century, data from physiologic studies had accumulated sufficiently to assemble a model for the function of receptors that must mediate the initial stimulus of tastant molecules in contact with the tongue. But the study of taste as a receptor-mediated event did not gain momentum until decades later when the actual receptor proteins and attendant signaling mechanisms were identified and localized to the highly specialized taste-responsive cells of the tongue. With those discoveries a new opportunity to examine taste as a function of receptor activity has come into focus. Pharmacology is the science designed specifically for the experimental interrogation and quantitative characterization of receptor function at all levels of inquiry from molecules to behavior. This review covers the history of some of the major concepts that have shaped thinking and experimental approaches to taste, the seminal discoveries that have led to elucidation of receptors for taste, and how applying principles of receptor pharmacology can enhance understanding of the mechanisms of taste physiology and perception.

Rapid Throughput Concentration-Response Analysis of Human Taste Discrimination.

Human taste threshold measurements often are used to infer tastant receptor functionality. However, taste thresholds can be influenced by receptor-independent variables. Examination of the full range of taste-active concentrations by taste discrimination has been hampered by logistics of testing multiple concentrations in replicate with human subjects. We developed an automated rapid throughput operant methodology for taste discrimination and applied it to concentration-response analysis of human taste. Tastant solutions (200 µl) drawn from a 96-well plate and self-administered to the tongue served as discriminative stimuli for money-reinforced responses on a touch-sensitive display. Robust concentration-response functions for "basic taste" stimuli were established, with particular focus on agonists of the taste 1 receptor member 2-taste 1 receptor member 3 heterodimer receptor (TAS1R2/R3). With a training cue of 100 mM sucrose, EC50 values of 56, 79, and 310 µM and 40 mM were obtained for rebaudioside A, sucralose, acesulfame potassium, and sucrose, respectively. Changing the sucrose training cue to 300 mM had no impact, but changing to 30 mM resulted in slight leftward shifts in potencies. A signal detection method also was used to determine values of d', a probabilistic value for discriminability, which indicated that 5 mM was near the limits of detection for sucrose. With repeated testing, both EC50 values and 5 mM sucrose d' values were established for each individual subject. The results showed little correspondence between threshold sensitivities and EC50 values for sucrose. We conclude that concentration-response analysis of taste discrimination provides a more reliable means of inferring receptor function than measurement of discriminability at the lowest detectable tastant concentrations. SIGNIFICANCE STATEMENT: Many inferences about human tastant receptor functionality have been made from taste threshold measurements, which can be influenced by variables unrelated to receptors. We herein report a new methodology that enables rigorous concentration-response analysis of human taste discrimination and its use toward quantitative characterization of tastant agonist activity. Our data suggest that taste discrimination concentration-response functions are a more reliable reflection of underlying receptor activity than threshold measures obtained at the lowest detectable tastant concentrations.

The maternal health behaviours of non-Irish nationals during pregnancy and the effect of time living in Ireland.

OBJECTIVES: Maternal health behaviours (MHBs) can influence pregnancy outcomes. Despite efforts internationally to encourage positive MHBs, women often fail to comply with pregnancy guidelines. International studies show differences in MHBs between nationalities and an effect of time spent in the host country. There is limited Irish data in this area, with no previous research relating to the effect of time in Ireland. STUDY DESIGN: This study is a cross-sectional analysis of the Growing Up in Ireland infant cohort, a nationally representative longitudinal study. METHODS: Examination of the MHBs of non-Irish nationals during pregnancy and the effect of time in Ireland on the said behaviours. RESULTS: An association was found between time spent in Ireland and increased alcohol consumption prevalence. Those living in Ireland for ≤5 years were 60.8% less likely to consume alcohol during pregnancy (0.000) and 29.3% less likely to take folic acid before conception (0.021). Those who smoked during pregnancy were 98.6% more likely to consume alcohol (0.000) and those who consumed alcohol were 95.2% more likely to smoke during pregnancy (0.000). CONCLUSIONS: The results demonstrate differences in MHBs and the influence of time living in Ireland. These findings are of relevance for policy and intervention planning to optimise pregnancy outcomes among non-nationals.

The role of the ALK receptor in cancer biology.

A vast array of oncogenic variants has been identified for anaplastic lymphoma kinase (ALK). Therefore, there is a need to better understand the role of ALK in cancer biology in order to optimise treatment strategies. This review summarises the latest research on the receptor tyrosine kinase ALK, and how this information can guide the management of patients with cancer that is ALK-positive. A variety of ALK gene alterations have been described across a range of tumour types, including point mutations, deletions and rearrangements. A wide variety of ALK fusions, in which the kinase domain of ALK and the amino-terminal portion of various protein partners are fused, occur in cancer, with echinoderm microtubule-associated protein-like 4 (EML4)-ALK being the most prevalent in non-small-cell lung cancer (NSCLC). Different ALK fusion proteins can mediate different signalling outputs, depending on properties such as subcellular localisation and protein stability. The ALK fusions found in tumours lack spatial and temporal regulation, which can also affect dimerisation and substrate specificity. Two ALK tyrosine kinase inhibitors (TKIs), crizotinib and ceritinib, are currently approved in Europe for use in ALK-positive NSCLC and several others are in development. These ALK TKIs bind slightly differently within the ATP-binding pocket of the ALK kinase domain and are associated with the emergence of different resistance mutation patterns during therapy. This emphasises the need to tailor the sequence of ALK TKIs according to the ALK signature of each patient. Research into the oncogenic functions of ALK, and fast paced development of ALK inhibitors, has substantially improved outcomes for patients with ALK-positive NSCLC. Limited data are available surrounding the physiological ligand-stimulated activation of ALK signalling and further research is needed. Understanding the role of ALK in tumour biology is key to further optimising therapeutic strategies for ALK-positive disease.

Multilocus phylogeography reveals nested endemism in a gecko across the monsoonal tropics of Australia.

Multilocus phylogeography can uncover taxonomically unrecognized lineage diversity across complex biomes. The Australian monsoonal tropics include vast, ecologically intact savanna-woodland plains interspersed with ancient sandstone uplands. Although recognized in general for its high species richness and endemism, the biodiversity of the region remains underexplored due to its remoteness. This is despite a high rate of ongoing species discovery, especially in wetter regions and for rock-restricted taxa. To provide a baseline for ongoing comparative analyses, we tested for phylogeographic structure in an ecologically generalized and widespread taxon, the gecko Heteronotia binoei. We apply coalescent analyses to multilocus sequence data (mitochondrial DNA and eight nuclear DNA introns) from individuals sampled extensively and at fine scale across the region. The results demonstrate surprisingly deep and geographically nested lineage diversity. Several intra-specific clades previously shown to be endemic to the region were themselves found to contain multiple, short-range lineages. To infer landscapes with concentrations of unique phylogeographic diversity, we probabilistically estimate the ranges of lineages from point data and then, combining these estimates with the nDNA species tree, estimate phyloendemism across the region. Highest levels of phyloendemism occur in northern Top End, especially on islands, across the topographically complex Arnhem escarpment, and across the sandstone ranges of the western Gulf region. These results drive home that deep phylogeographic structure is prevalent in tropical low-dispersal taxa, even ones that are ubiquitous across geography and habitats.

Generation of 64 GBd 4ASK signals using a silicon-organic hybrid modulator at 80°C.

We demonstrate a silicon-organic hybrid (SOH) Mach-Zehnder modulator (MZM) generating four-level amplitude shift keying (4ASK) signals at symbol rates of up to 64 GBd both at room temperature and at an elevated temperature of 80°C. The measured line rate of 128 Gbit/s corresponds to the highest value demonstrated for silicon-based MZM so far. We report bit error ratios of 10-10 (64 GBd BPSK), 10-5 (36 GBd 4ASK), and 4 × 10-3 (64 GBd 4ASK) at room temperature. At 80 °C, the respective bit error ratios are 10-10, 10-4, and 1.3 × 10-2. The high-temperature experiments were performed in regular oxygen-rich ambient atmosphere.

Integrated optical frequency shifter in silicon-organic hybrid (SOH) technology.

We demonstrate for the first time a waveguide-based frequency shifter on the silicon photonic platform using single-sideband modulation. The device is based on silicon-organic hybrid (SOH) electro-optic modulators, which combine conventional silicon-on-insulator waveguides with highly efficient electro-optic cladding materials. Using small-signal modulation, we demonstrate frequency shifts of up to 10 GHz. We further show large-signal modulation with optimized waveforms, enabling a conversion efficiency of -5.8 dB while suppressing spurious side-modes by more than 23 dB. In contrast to conventional acousto-optic frequency shifters, our devices lend themselves to large-scale integration on silicon substrates, while enabling frequency shifts that are several orders of magnitude larger than those demonstrated with all-silicon serrodyne devices.

Genome-wide single nucleotide polymorphism heritability of nicotine dependence as a multidimensional phenotype.

BACKGROUND: Heritability estimates from twin studies of the multi-faceted phenotype of nicotine dependence (ND) range from moderate to high (31-60%), but vary substantially based on the specific ND-related construct examined. The current study estimated the aggregate role of common genetic variants on key ND constructs. METHOD: Genomic-relationship-matrix restricted maximum likelihood (GREML) was used to decompose phenotypic variance across multiple ND indices using 796 125 polymorphisms from 2346 unrelated 'lifetime ever smokers' of European ancestry. Measures included DSM-IV ND and Fagerström Test for Nicotine Dependence (FTND) summary measures and constituent constructs (e.g. withdrawal severity, tolerance, heaviness of smoking and time spent smoking). Exploratory and confirmatory factor models were used to describe the covariance structure across ND measures; resulting factor(s) were the subject(s) of GREML analyses. RESULTS: Factor models indicated highly correlated DSM-IV and FTND factors for ND (0.545, 95% confidence interval 0.50-0.60) that could be represented as a higher-order factor (NIC DEP). Additive genetic influence on NIC DEP was 33% (s.e. = 0.14, p = 0.009). Post-hoc analyses indicated moderate genetic effects on the DSM-IV (34%, s.e. = 0.14, p = 0.008) and FTND (26%, s.e. = 0.14, p = 0.032) factors, both of which were influenced by the same genetic effects (r G-SNP = 1.00, s.e. = 0.09, p < 0.00001). CONCLUSIONS: Overall, common single nucleotide polymorphisms accounted for a large proportion of the genetic influences on ND-related phenotypes that have been observed in twin studies. Genetic contributions across distinct ND scales were largely influenced by shared genetic factors.

Note: Production of silver nanoclusters using a Matrix-Assembly Cluster Source with a solid CO2 matrix.

One of the main limitations to the application of clusters on applied areas is the limited production; therefore, it is of great interest to up scale cluster production while keeping good size control. The Matrix-Assembly Cluster Source is a new high flux cluster source, which exploits cluster formation inside a solid rare gas matrix that is sputtered by an ion beam. Clusters are formed and ejected in this process. Here we report the production of Ag clusters when the rare gas is replaced by CO2 for the matrix formation at 20 K. Size distributions were determined from scanning transmission electron microscopy analysis of samples with four different metal loadings, 4%, 8%, 14%, and 23% of Ag atoms to CO2 molecules, and two ion beam energies, 1 keV and 2 keV. Cluster mean size showed weak dependence on metal loading, being ≈80 atoms for the first three concentrations, whereas the change in ion beam energy has caused cluster mean size to shift from 86 to 160 atoms. The results are interpreted in terms of bonding energy between Ag and CO2 and compared to the rare gas (Ar) matrix.

Plasmonic-organic hybrid (POH) modulators for OOK and BPSK signaling at 40 Gbit/s.

We report on high-speed plasmonic-organic hybrid Mach-Zehnder modulators comprising ultra-compact phase shifters with lengths as small as 19 µm. Choosing an optimum phase shifter length of 29 µm, we demonstrate 40 Gbit/s on-off keying (OOK) modulation with direct detection and a BER < 6 × 10(-4). Furthermore, we report on a 29 µm long binary-phase shift keying (BPSK) modulator and show that it operates error-free (BER < 1 × 10(-10)) at data rates up to 40 Gbit/s and with an energy consumption of 70 fJ/bit.

Establishment of a 100-seed weight quantitative trait locus-allele matrix of the germplasm population for optimal recombination design in soybean breeding programmes.

A representative sample comprising 366 accessions from the Chinese soybean landrace population (CSLRP) was tested under four growth environments for determination of the whole-genome quantitative trait loci (QTLs) system of the 100-seed weight trait (ranging from 4.59g to 40.35g) through genome-wide association study (GWAS). A total of 116 769 single nucleotide polymorphisms (SNPs) were identified and organized into 29 121 SNP linkage disequilibrium blocks (SNPLDBs) to fit the property of multiple alleles/haplotypes per locus in germplasm. An innovative two-stage GWAS was conducted using a single locus model for shrinking the marker number followed by a multiple loci model utilizing a stepwise regression for the whole-genome QTL identification. In total, 98.45% of the phenotypic variance (PV) was accounted for by four large-contribution major QTLs (36.33%), 51 small-contribution major QTLs (43.24%), and a number of unmapped minor QTLs (18.88%), with the QTL×environment variance representing only 1.01% of the PV. The allele numbers of each QTL ranged from two to 10. A total of 263 alleles along with the respective allele effects were estimated and organized into a 263×366 matrix, giving the compact genetic constitution of the CSLRP. Differentiations among the ecoregion matrices were found. No landrace had alleles which were all positive or all negative, indicating a hidden potential for recombination. The optimal crosses within and among ecoregions were predicted, and showed great transgressive potential. From the QTL system, 39 candidate genes were annotated, of which 26 were involved with the gene ontology categories of biological process, cellular component, and molecular function, indicating that diverse genes are involved in directing the 100-seed weight.

Pt Diffusion Dynamics for the Formation Cr-Pt Core-Shell Nanoparticles.

Layered core-shell bimetallic Cr-Pt nanoparticles were prepared by the formation and later reduction of an intermediate Pt-ion-containing supramolecular complex onto preformed Cr nanoparticles. The resultant nanoparticles were characterized by X-ray diffraction analysis, transmission electron microscopy, X-ray photoelectron spectroscopy, and aberration-corrected scanning transmission electron microscopy. The results are consistent with the presence of Pt diffusion during or after bimetallic nanoparticle formation, which has resulted in a Pt/Cr-alloyed core and shell. We postulate that such Pt diffusion occurs by an electric-field-assisted process according to Cabrera-Mott theory and that it originates from the low work function of the preformed oxygen-defective Cr nanoparticles and the rather large electron affinity of Pt.

Effects of graduated compression stockings on skin temperature after running.

High skin temperatures reduce the thermal gradient between the core and the skin and they can lead to a reduction in performance and increased risk of injury. Graduated compression stockings have become popular among runners in the last years and their use may influence the athlete's thermoregulation. The aim of this study was to investigate the effects of graduated compression stockings on skin temperature during running in a moderate indoor environment. Forty-four runners performed two running tests lasting 30min (10min of warm-up and 20min at 75% of their maximal aerobic speed) with and without graduated compressive stockings. Skin temperature was measured in 12 regions of interest on the lower limb by infrared thermography before and after running. Heart rate and perception of fatigue were assessed during the last minute of the running test. Compression stockings resulted in greater increase of temperature (p=0.002 and ES=2.2, 95% CI [0.11-0.45°C]) not only in the body regions in contact (tibialis anterior, ankle anterior and gastrocnemius) but also in the body regions that were not in contact with the garment (vastus lateralis, abductor and semitendinosus). No differences were observed between conditions in heart rate and perception of fatigue (p>0.05 and ES<0.8). In conclusion, running with graduated compression stockings produces a greater increase of skin temperature without modifying the athlete's heart rate and perception of fatigue.

Low-power silicon-organic hybrid (SOH) modulators for advanced modulation formats.

We demonstrate silicon-organic hybrid (SOH) electro-optic modulators that enable quadrature phase-shift keying (QPSK) and 16-state quadrature amplitude modulation (16QAM) with high signal quality and record-low energy consumption. SOH integration combines highly efficient electro-optic organic materials with conventional silicon-on-insulator (SOI) slot waveguides, and allows to overcome the intrinsic limitations of silicon as an optical integration platform. We demonstrate QPSK and 16QAM signaling at symbol rates of 28 GBd with peak-to-peak drive voltages of 0.6 V(pp). For the 16QAM experiment at 112 Gbit/s, we measure a bit-error ratio of 5.1 × 10⁻5 and a record-low energy consumption of only 19 fJ/bit.

Silicon-organic hybrid (SOH) frequency comb sources for terabit/s data transmission.

We demonstrate frequency comb sources based on silicon-organic hybrid (SOH) electro-optic modulators. Frequency combs with line spacings of 25 GHz and 40 GHz are generated, featuring flat-top spectra with less than 2 dB power variations over up to 7 lines. The combs are used for WDM data transmission at terabit/s data rates and distances of up to 300 km.

Enhanced immobilization of gold nanoclusters on graphite.

The immobilization of individual biological molecules by metal nanoparticles requires that the particles themselves be immobilized. We introduce a new technique for immobilization of gold clusters based on their binding to small tunnels in a graphite support, themselves created by the implantation of small clusters. These tunnels are shown to perform as more effective cluster immobilization sites than point defects on the surface of graphite. The method is tested with atomic force microscopy (AFM) (both contact and noncontact mode) scanning. Size-selected clusters with 923, 561, 309, and 147 atoms have been immobilized and imaged with high-resolution, noncontact AFM.

Three-dimensional atomic-scale structure of size-selected gold nanoclusters.

An unambiguous determination of the three-dimensional structure of nanoparticles is challenging. Electron tomography requires a series of images taken for many different specimen orientations. This approach is ideal for stable and stationary structures. But ultrasmall nanoparticles are intrinsically structurally unstable and may interact with the incident electron beam, constraining the electron beam density that can be used and the duration of the observation. Here we use aberration-corrected scanning transmission electron microscopy, coupled with simple imaging simulation, to determine with atomic resolution the size, three-dimensional shape, orientation and atomic arrangement of size-selected gold nanoclusters that are preformed in the gas phase and soft-landed on an amorphous carbon substrate. The structures of gold nanoclusters containing 3096 atoms can be identified with either Ino-decahedral, cuboctahedral or icosahedral geometries. Comparison with theoretical modelling of the system suggests that the structures are consistent with energetic considerations. The discovery that nanoscale gold particles function as active and selective catalysts for a variety of important chemical reactions has provoked much research interest in recent years. We believe that the detailed structure information we provide will help to unravel the role of these nanoclusters in size- and structure-specific catalytic reactions. We note that the technique will be of use in investigations of other supported ultrasmall metal cluster systems.

Best Practices in Clinical Education: A Site Visit Decision-Making Model in Physical Therapist Education.

Stakeholders in health science education engage in site visits during student clinical education experiences, which may occur in person or remotely via videoconference, telephone, or email. Significant variability in practice highlights the need for a more consistent approach to conducting site visits based on evidence-based best practices. Site visits can be burdensome to both clinical and academic stakeholders considering the significant time and resources needed to conduct them effectively. Despite these obstacles, site visits have been shown to add value to the clinical experience for all parties involved. This paper presents the available literature in health science education regarding clinical site visits and describes how it was used to develop and implement a model of best practice for conducting clinical site visits in physical therapist education. The Site Visit Decision-Making Model is based upon findings from contemporary research exploring the interests of each stakeholder, as well as the multifaceted and purposeful decision-making process that takes place when conducting site visits in physical therapist clinical education. Implementation of this model may assist academic stakeholders in health science education in prioritizing which methods of communication for conducting site visits are most effective and efficient.