Background: Hereditary transthyretin-mediated (hATTR) amyloidosis is a multi-systemic, heterogenous, life-threatening disease. Patisiran resulted in significant improvement in neuropathy and QoL at 18-months compared to placebo, and was generally well-tolerated in the Phase 3 APOLLO study. Methods: Multi-center, OLE study to evaluate the efficacy and safety of long-term patisiran dosing for ≤ 5 years in hATTR amyloidosis patients with polyneuropathy who have completed the APOLLO study (NCT02510261). Endpoints include safety, tolerability and long-term efficacy of patisiran. Measures of clinical benefit are the same endpoints used in APOLLO including changes in mNIS+7 composite neuropathy impairment score and QoL (Norfolk QoL-DN) Results: As of December 2017, 184 of 186 (99%) patients who completed APOLLO and 25 patients from the Ph 2 OLE study enrolled in the Global OLE study. Baseline data for 211(APOLLO/placebo, n=49; APOLLO/patisiran, n=137 and patisiran Ph 2 OLE, n=25) patients included: median age 61 years (26-84); 74% males; 46% V30M. Interim safety data and 12-month efficacy results will be presented. Conclusions: The global OLE study includes a diverse population of hATTR amyloidosis patients. Interim data will include the long-term safety and maintenance of effect in patients continuing on patisiran, as well as the impact of treatment with patisiran on patients previously treated with placebo.

Triploid and pentaploid breeding is of great importance in agricultural production, but it is not always easy to obtain double ploidy parents. However, in fishes, chromosome ploidy is diversiform, which may provide natural parental resources for triploid and pentaploid breeding. Both tetraploid and hexaploid exist in Schizothorax fishes, which were thought to belong to different subfamilies with tetraploid Percocypris fishes in morphology, but they are sister genera in molecule. Fortunately, the pentaploid hybrid fishes have been successfully obtained by hybridization of Schizothorax wangchiachii (♀, 2n = 6X = 148) × Percocypris pingi (♂, 2n = 4X = 98). To understand the genetic and morphological difference among the hybrid fishes and their parents, four methods were used in this study: morphology, karyotype, red blood cell (RBC) DNA content determination and inter-simple sequence repeat (ISSR). In morphology, the hybrid fishes were steady, and between their parents with no obvious preference. The chromosome numbers of P. pingi have been reported as 2n = 4X = 98. In this study, the karyotype of S. wangchiachii was 2n = 6X = 148 = 36m + 34sm + 12st + 66t, while that the hybrid fishes was 2n = 5X = 123 = 39m + 28sm + 5st + 51t. Similarly, the RBC DNA content of the hybrid fishes was intermediate among their parents. In ISSR, the within-group genetic diversity of hybrid fishes was higher than that of their parents. Moreover, the genetic distance of hybrid fishes between P. pingi and S.wangchiachii was closely related to that of their parental ploidy, suggesting that parental genetic material stably coexisted in the hybrid fishes. This is the first report to show a stable pentaploid F1 hybrids produced by hybridization of a hexaploid and a tetraploid in aquaculture.

To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.

In this paper, a novel single-cavity triangular substrate-integrated waveguide (TSIW) dual-band filter loading a complementary triangular split ring resonator (CTSRR) is proposed, which has three transmission zeros (TZs) in the stopband in total. The dual-band response is achieved by the CTSRR and the degenerate modes of the TSIW cavity. In order to control the TZs, we propose two adjustment techniques, shift feeding technique and adding via perturbation. In addition, the CTSRR etched on the surface can produce a new TZ in the upper first-passband. Finally, a dual-band filter with three TZs is simulated, fabricated, and measured. There is a good agreement between the simulated results and measured ones.

Dietary protein restriction is one of the effective ways to reduce post-weaning diarrhoea and intestinal fermentation in piglets, but it may also reduce growth performance. The compensatory growth induced by subsequent protein realimentation may solve the issue. However, little research has been done on the impact of protein realimentation on the gut. In this study, the effects of protein restriction and realimentation on ileal morphology, ileal microbial composition and metabolites in weaned piglets were investigated. Thirty-six 28-day-old weaned piglets with an average body weight of 6.47 ± 0.04 kg were randomly divided into a control group and a treatment group. The CP level in the diet of the control group was 18.83% for the entire experimental period. The piglets in the treatment group were fed 13.05% CP between days 0 and 14 and restored to a diet of 18.83% CP for days 14 to 28. On day 14 and 28, six pigs from each group were sacrificed and sampled. It was found that the abundance of Lactobacillus and Salmonella in the ileal digesta was significantly lower in the treatment group than the control group on day 14, whereas the abundance of Clostridium sensu stricto 1, Streptococcus, Halomonas and Pseudomonas significantly increased in the ileal digesta of the treatment group on day 14 compared with the control group. In addition, reduced concentrations of lactic acid, total short-chain fatty acids (total SCFAs), total branched chain fatty acids, ammonia and impaired ileal morphology and mucosal barrier were observed in the treatment group on day 14. However, diarrhoea levels decreased in the treatment group throughout the experiment. During the succedent protein realimentation stage, the treatment group demonstrated compensatory growth. Compared with the control group, the treatment group showed increased abundance of Lactobacillus and reduced abundance of Salmonella, Halomonas and Pseudomonas in the ileum on day 28. The concentrations of lactic acid and total SCFAs increased significantly, whereas the concentration of ammonia remained at a lower level in the treatment group on day 28 compared with the control group. Overall, protein realimentation could improve ileal morphology and barrier functions and promote ileal digestive and absorptive functions. In conclusion, ileal microbial composition and metabolites could change according to dietary protein restriction and realimentation and eventually influence ileal morphology and barrier functions.

All-printed electronics is the key technology to ultra-low-cost, large-area electronics. As a critical step in this direction, we demonstrate that femtosecond laser processing (sintering and ablation) of solution deposited metal nanoparticles enables direct metal patterning at low-temperature with ultra high resolution (∼300nm) to overcome the resolution limitation of the current inkjet direct writing processes.

This could be explained by the combined effects of novel properties of metal nanoparticles such as melting temperature drop, strong absorption of the incident laser beam at surface plasmon mode, lower conductive heat transfer loss, and the relatively weak bonding between nanoparticles. Local thermal control of the laser sintering process could minimize the heat-affected zone and the thermal damage to the substrate and further enhance the resolution of the process. This local nanoparticle deposition and energy coupling enable an environmentally friendly and cost-effective process as well as a low-temperature manufacturing sequence to realize large-area, flexible electronics on polymer substrates.

The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.

OBJECTIVES/SPECIFIC AIMS: The objective of this study is to assess differences in outcomes between African Americans (AAs) and whites along the HCV care cascade. Primary outcome was retention in the HCV care cascade, measured in two ways. For viral RNA confirmation, retention was a percentage of those having screened antibody reactive. For hepatic ultrasound, primary care, HCV specialty clinic, treatment initiation, and sustained viral load (SVR), retention was a percentage of those found chronically infected by positive RNA viral load. Secondary outcome was time to follow-up from antibody screening to each subsequent step in the care cascade. METHODS/STUDY POPULATION: A retrospective cohort study was performed. AA and white patients who tested HCV antibody reactive from March to October 2015 at the University Medical Center (UMC) Emergency Department in New Orleans, LA were included in this study. Outcomes were assessed using the HCV Continuum of Care model, delineating successive stages of care from identification to cure. RESULTS/ANTICIPATED RESULTS: A total of 728 patients screened HCV antibody reactive, including 446 AAs and 282 whites. AAs (53.5 years, SD 10.2) were disproportionately older than whites (46.7 years, SD 11.9) (p <0.001), more likely to be insured (89.2% vs 78.7%, p<0.001), had higher rates of Medicare (28.0% vs 12.1%, p<0.001), and less frequent history of intravenous drug use (IVDU) (32.3% vs 46.1%, p<0.001). For AAs, retention in the treatment cascade was 96.2% for viral RNA confirmation, 50.9% for hepatic ultrasound, 26.8% for primary care, 35.2% for HCV specialty clinic, 14.5% for treatment initiation, and 9.6% for sustained viral response (SVR). Among whites, retention in the treatment cascade was 96.8% for viral RNA confirmation, 37.8% for hepatic ultrasound, 16.1% for primary care, 23.3% for HCV specialty clinic, 8.8% for treatment initiation, and 7.8% for SVR. AAs had a higher likelihood of receiving a hepatic ultrasound (OR=1.70; CI=1.19-2.25; p<0.005), following up with primary care (OR = 1.91, CI=1.21-3.02, p<0.005), and attending the viral hepatitis specialty clinic (OR=1.79, CI=1.20-2.68, p<0.005), as compared to their white counterparts. After adjusting for age, insurance, and history of IVDU, AAs did not have a higher likelihood of receiving a hepatic ultrasound (aOR=1.09, CI=0.995-1.19) or seeking primary care (aOR=1.05, CI=0.98-1.14). AAs had attenuated odds of attending viral hepatitis specialty clinic (aOR=1.09, CI = 1.01-1.19). There was no statistically significant difference in follow-up time in the treatment cascade for AAs versus whites. DISCUSSION/SIGNIFICANCE OF IMPACT: Race alone cannot explain differences in achievement along the care cascade. Significant differences in retention along the HCV care cascade appear to be related primarily to differences in age and insurance status. In our population, older AAs are disproportionately insured through Medicare, thereby expanding their access to health resources. Their white counterparts are younger and more uninsured, leading to decreased access to care and ability to attend HCV follow-up appointments. ED HCV screening programs are still in their infancy and have opportunities to improve their linkage to care rates. Additional interventions are needed to better connect patients screened positive in the ED to HCV specialist care, preserving equity across racial groups.

Life-history theory predicts a trade-off between the juvenile growth rate and adult traits related to survival. However, this hypothesized negative correlation is difficult to test robustly because many trade-offs are mild, and environmental variables, such as changes in nutrient availability, can ameliorate the trade-off or make it more pronounced. Thus, it is reasonable to expect that the expression of the trade-off can be condition-dependent. In the present study, we first examined the pre-adult life-history traits of the cotton bollworm, Helicoverpa armigera, collected from northern, central, and southern China at different temperatures. We found that the northern China population has a significantly shorter pre-adult developmental time and higher growth rate than the southern China population as a result of adaptation to the decreased seasonal length. Then, we tested for a trade-off between the juvenile growth rate and adult lifespan in different temperature and nutrient conditions. We found a negative relationship between juvenile growth rate and adult lifespan under starvation or desiccation conditions; however, a continuous supply of sugar can diminish or obviate the apparent negative relationship, in which the adult lifespan did not show a significant difference in most of the comparisons. These results suggested a resource-mediated trade-off may exist between juvenile growth rate and adult lifespan. However, the adult size may have some positive effect on the lifespan under starvation and desiccation conditions, which may affect the expression of trade-off.

Bullying has been understudied among preschool children, especially those from Chinese American families. Previous research has also neglected the dimensional effects of psychological control on child bullying development. This study examined two psychological control dimensions, love withdrawal and guilt induction, and their effects on children's bullying aggressive behavior using a longitudinal design. Participants were first-generation Chinese American mothers (N = 133; mean age [Mage] = 37.82) and their preschool children (Mage = 4.48). Chinese immigrant mothers reported their psychologically controlling parenting and teachers rated children's bullying aggressive behaviors in the school setting. Confirmatory factor analyses were conducted to establish the psychometric properties and cross-wave measurement equivalence of the study constructs. Cross-lagged structural equation modeling analysis indicated that maternal love withdrawal prospectively predicted more bullying aggressive behavior, whereas guilt induction predicted less bullying aggressive behavior in children 6 months later. These results held after controlling for the initial level of children's problem behaviors and demographic variables (child age, gender, and maternal education). For child effects, child bullying aggressive behavior predicted more maternal guilt induction over time but not love withdrawal. Our findings highlight the importance of construct specificity and cultural context in understanding associations between parenting and child development.

Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.

Coastal lake sediments are valuable paleoclimate archives provided that they can be accurately dated. Here, we report radiocarbon ages of bulk sediment organic matter (OM), plants, shells, particulate OM, and dissolved OM from coastal lakes in Florida. Bulk sediment OM yielded ages that are consistently older than contemporaneous plants and shells, indicating significant radiocarbon deficiencies in sedimentary OM in these lakes. The data show that the OM radiocarbon deficiency varies over time and with location, making it impossible to determine a proper correction factor for radiocarbon ages of bulk sediments from these lakes. As a result, we consider ages obtained from bulk sediment OM from these lakes unreliable. The age reversals in bulk sediment OM observed in the sediment cores are likely caused by rapid increases in erosion and sedimentation resulting from large storm events. The data also show that sedimentation rate can vary considerably within a given lake, implying that an age-depth model established for one core cannot be directly applied to other cores despite their close proximity. Analyses of shells from one of the lakes suggest that fresh/brackish-water shells may serve as a good substrate for radiocarbon dating owing to a small reservoir effect on inorganic carbon.

A stable reference gene is a key prerequisite for accurate assessment of gene expression. At present, the real-time reverse transcriptase quantitative polymerase chain reaction has been widely used in the analysis of gene expression in a variety of organisms. Neoseiulus barkeri Hughes (Acari: Phytoseiidae) is a major predator of mites on many important economically crops. Until now, however, there are no reports evaluating the stability of reference genes in this species. In view of this, we used GeNorm, NormFinder, BestKeeper, and RefFinder software tools to evaluate the expression stability of 11 candidate reference genes in developmental stages and under various abiotic stresses. According to our results, β-ACT and Hsp40 were the top two stable reference genes in developmental stages. The Hsp60 and Hsp90 were the most stable reference genes in various acaricides stress. For alterations in temperature, Hsp40 and α-TUB were the most suitable reference genes. About UV stress, EF1α and α-TUB were the best choice, and for the different prey stress, β-ACT and α-TUB were best suited. In normal conditions, the β-ACT and α-TUB were the two of the highest stable reference genes to respond to all kinds of stresses. The current study provided a valuable foundation for the further analysis of gene expression in N. barkeri.

Hemostasis, a process which causes bleeding to stop, can be enhanced using chitosan; but the detailed mechanism is unclear. Red blood cells (RBCs) adhere to chitosan because of their opposite charges, but the adhesion force is small, 3.83 pN as measured here using an optical tweezer, such that the direct adhesion cannot be the sole cause for hemostasis. However, it was observed in this study that layer structures of aggregated RBCs were formed next to chitosan objects in both static and flowing environments, but not formed next to cotton and rayon yarns. The layer structure is the clue for the initiation of hemostatsis. Through the supporting measurements of zeta potentials of RBCs and pH's using blood-chitosan mixtures, it is proposed here that the formation of the RBC layer structure next to chitosan objects is due to the reduction of repulsive electric double layer force between RBCs, because of the association of H+ deprotonated from chitosan with COO− on RBC membrane, under the DLVO (Derjaguin-Landau-Verwey-Overbeek) theory. The results are beneficial for designing effective chitosan-based wound dressings, and also for general biomedical applications.