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Seasonal influenza virus epidemics have a major impact on healthcare systems. Data on population susceptibility to emerging influenza virus strains during the interepidemic period can guide planning for resource allocation of an upcoming influenza season. This study sought to assess the population susceptibility to representative emerging influenza virus strains collected during the interepidemic period. The microneutralisation antibody titers (MN titers) of a human serum panel against representative emerging influenza strains collected during the interepidemic period before the 2018/2019 winter influenza season (H1N1-inter and H3N2-inter) were compared with those against influenza strains representative of previous epidemics (H1N1-pre and H3N2-pre). A multifaceted approach, incorporating both genetic and antigenic data, was used in selecting these representative influenza virus strains for the MN assay. A significantly higher proportion of individuals had a ⩾four-fold reduction in MN titers between H1N1-inter and H1N1-pre than that between H3N2-inter and H3N2-pre (28.5% (127/445) vs. 4.9% (22/445), P < 0.001). The geometric mean titer (GMT) of H1N1-inter was significantly lower than that of H1N1-pre (381 (95% CI 339–428) vs. 713 (95% CI 641–792), P < 0.001), while there was no significant difference in the GMT between H3N2-inter and H3N2-pre. Since A(H1N1) predominated the 2018–2019 winter influenza epidemic, our results corroborated the epidemic subtype.
Ceramics are strong but brittle. According to the classical theories, ceramics are brittle mainly because dislocations are suppressed by cracks. Here, the authors report the combined elastic and plastic deformation measurements of nanoceramics, in which dislocation-mediated stiff and ductile behaviors were detected at room temperature. In the synchrotron-based deformation experiments, a marked slope change is observed in the stress–strain relationship of MgAl2O4 nanoceramics at high pressures, indicating that a deformation mechanism shift occurs in the compression and that the nanoceramics sample is elastically stiffer than its bulk counterpart. The bulk-sized MgAl2O4 shows no texturing at pressures up to 37 GPa, which is compatible with the brittle behaviors of ceramics. Surprisingly, substantial texturing is seen in nanoceramic MgAl2O4 at pressures above 4 GPa. The observed stiffening and texturing indicate that dislocation-mediated mechanisms, usually suppressed in bulk-sized ceramics at low temperature, become operative in nanoceramics. This makes nanoceramics stiff and ductile.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Much of the interest in youth at clinical high risk (CHR) of psychosis has been in understanding conversion. Recent literature has suggested that less than 25% of those who meet established criteria for being at CHR of psychosis go on to develop a psychotic illness. However, little is known about the outcome of those who do not make the transition to psychosis. The aim of this paper was to examine clinical symptoms and functioning in the second North American Prodrome Longitudinal Study (NAPLS 2) of those individuals whose by the end of 2 years in the study had not developed psychosis.
In NAPLS-2 278 CHR participants completed 2-year follow-ups and had not made the transition to psychosis. At 2-years the sample was divided into three groups – those whose symptoms were in remission, those who were still symptomatic and those whose symptoms had become more severe.
There was no difference between those who remitted early in the study compared with those who remitted at one or 2 years. At 2-years, those in remission had fewer symptoms and improved functioning compared with the two symptomatic groups. However, all three groups had poorer social functioning and cognition than healthy controls.
A detailed examination of the clinical and functional outcomes of those who did not make the transition to psychosis did not contribute to predicting who may make the transition or who may have an earlier remission of attenuated psychotic symptoms.
Layered transition metal dichalcogenides (TMDs) have attracted interest due to their promise for future electronic and optoelectronic technologies. As one approaches the two-dimensional (2D) limit, thickness and local topology can greatly influence the macroscopic properties of a material. To understand the unique behavior of TMDs it is therefore important to identify the number of atomic layers and their stacking in a sample. The goal of this work is to extract the thickness and stacking sequence of TMDs directly by matching experimentally recorded high-angle annular dark-field scanning transmission electron microscope images and convergent-beam electron diffraction (CBED) patterns to quantum mechanical, multislice scattering simulations. Advantageously, CBED approaches do not require a resolved lattice in real space and are capable of neglecting the thickness contribution of amorphous surface layers. Here we demonstrate the crystal thickness can be determined from CBED in exfoliated 1T-TaS2 and 2H-MoS2 to within a single layer for ultrathin ≲9 layers and ±1 atomic layer (or better) in thicker specimens while also revealing information about stacking order—even when the crystal structure is unresolved in real space.
OBJECTIVES/SPECIFIC AIMS: The aim of this study is to determine whether quantitative measures of knee structures including effusion, bone marrow lesions, cartilage, and meniscal damage can improve upon an existing model of demographic and clinical characteristics to classify accelerated knee osteoarthritis (AKOA). METHODS/STUDY POPULATION: We conducted a case-control study using data from baseline and four annual follow-up visits from the osteoarthritis initiative. Participants had no radiographic knee osteoarthritis (KOA) at baseline. AKOA is defined as progressing from no KOA to advance-stage KOA in at least 1 knee within 48 months. AKOA knees were matched 1:1 based on sex to (1) participants who did not develop KOA within 48 months and (2) participants who developed KOA but not AKOA. Analyses were person based. Classification and regression tree analysis was used to determine the important variables and percent of variance explained. RESULTS/ANTICIPATED RESULTS: A previous classification and regression tree analysis found that age, BMI, serum glucose, and femorotibial angle explained 31% of the variability between those who did and did not develop AKOA. Including structural measurements as candidate variables yielded a model that included effusion, BMI, serum glucose, cruciate ligament degeneration and coronal slope and explained 39% of the variability. DISCUSSION/SIGNIFICANCE OF IMPACT: Knee structural measurements improve classification of participants who developed AKOA Versus those who did not. Further research is needed to better classify patients at risk for AKOA.
Whether there are distinct subtypes of schizophrenia is an important issue to advance understanding and treatment of schizophrenia.
To understand and treat individuals with schizophrenia, the aim was to advance understanding of differences between individuals, whether there are discrete subtypes, and how fist-episode patients (FEP) may differ from multiple episode patients (MEP).
These issues were analysed in 687 FEP and 1880 MEP with schizophrenia using the Positive and Negative Syndrome Scale for (PANSS) schizophrenia before and after antipsychotic medication for 6 weeks.
The seven Negative Symptoms were correlated with each other and with P2 (conceptual disorganisation), G13 (disturbance of volition), and G7 (motor retardation). The main difference between individuals was in the cluster of seven negative symptoms, which had a continuous unimodal distribution. Medication decreased the PANSS scores for all the symptoms, which were similar in the FEP and MEP groups.
The negative symptoms are a major source of individual differences, and there are potential implications for treatment.
The effect of the ingestion of diets containing either myo-inositol or exogenous phytase on plasma metabolites was examined using 29 kg barrows. The diets were: control (maize, soya, rapeseed, rice bran), control plus 2 g/kg myo-inositol, control plus 1000 phytase units (FYT)/kg or 3000 FYT/kg exogenous phytase. Pigs were housed in a PigTurn device and blood was collected, from jugular catheters, via an automated system at −30, (30 min before feeding), 0, 15, 30, 45, 60, 90, 120, 150, 180, 240, 300 and 360 min post-feeding. The addition of 2 g/kg myo-inositol to the basal diet resulted in an increase in plasma myo-inositol concentration that was evident 45–60 min after diet introduction and persisted to 360 min post-feeding. Similarly, supplementation of the basal diet with either 1000 or 3000 FYT/kg exogenous phytase resulted in an increase in plasma myo-inositol concentration that was still rising 360 min post-feeding. Plasma P concentration was increased over time by the addition of 1000 and 3000 FYT/kg phytase, but not by the addition of myo-inositol. Other plasma metabolites examined were not affected by dietary treatment. It can be concluded that oral delivery of myo-inositol results in rapid increase in plasma myo-inositol concentrations that peak approximately 45–60 min after feeding. Use of supplemental phytase achieves similar increases in myo-inositol concentration in plasma but the appearance is more gradual. Furthermore, supplementation of pig diets with exogenous phytase results in rapid appearance of P in plasma that may be sustained over time relative to diets with no added phytase.
Family history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.
We studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.
Using harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.
Combining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
The objective of this investigation is the determination of absolute parallaxes and proper motions with respect to faint galaxies for three fields at mid galactic latitudes and one field near the south galactic pole. The three mid galactic latitude fields were photographed on a IIIa-J + GG385 plate/filter combination by van Altena at the prime focus of the KPNO 4-meter in the mid 1970s, while the south polar region was photographed on a IIIa-F + RG610 plate/filter combination by van Altena and C.E. Lopez (Univ. of San Juan, Argentina) at the prime focus of the CTIO 4-meter; all plates were hypersensitized by baking and exposed to the sky limit. In this paper we report on the progress of an investigation of the mid galactic latitude field at R.A. = 7h 07m 31s and Dec. = +7o 19.7′ (1950) which contains the faint binary white dwarf LP543-32/33. Preliminary measurements of selected stars in this field were made some time ago and a parallax of the white dwarf binary were published by van Altena and Mora (1977). Those measurements showed that the plates were of very high astrometric quality and that it would be possible to obtain accurate parallaxes for very faint stars.
The transient impact hypothesis was extended, and the oblique collision model was established by considering the tangential slip. In order to solve this problem, the oblique-impact equations for cam-follower were transformed into a linear complementarity problem. Impulsive control method was employed to control or anti-control the nonlinear responses. The simulation results show that the cam-follower system performs very complex nonlinear characteristics, such as period, quasi-period and chaos responses. Using the impulsive control method, the nonlinear responses of the cam-follower system can be controlled to P(n, n) and P(∞, n) or anti-controlled to chaos.
Ocular toxoplasmosis (OT) caused by Toxoplasma gondii is a major cause of infectious uveitis, however little is known about its immunopathological mechanism. Susceptible C57BL/6 (B6) and resistant BALB/c mice were intravitreally infected with 500 tachyzoites of the RH strain of T. gondii. B6 mice showed more severe ocular pathology and higher parasite loads in the eyes. The levels of galectin (Gal)-9 and its receptors (Tim-3 and CD137), interferon (IFN)-γ, IL-6 and IL-10 were significantly higher in the eyes of B6 mice than those of BALB/c mice; however, the levels of IFN-α and -β were significantly decreased in the eyes and CLNs of B6 mice but significantly increased in BALB/c mice after infection. After blockage of galectin–receptor interactions by α-lactose, neither ocular immunopathology nor parasite loads were different from those of infected BALB/c mice without α-lactose treatment. Although the expressions of Gal-9/receptor were significantly increased in B6 mice and Gal-1 and -3 were upregulated in both strains of mice upon ocular T. gondii infection, blockage of galectins did not change the ocular pathogenesis of genetic resistant BALB/c mice. However, IFN-α and -β were differently expressed in B6 and BALB/c mice, suggesting that type I IFNs may play a protective role in experimental OT.
The largest ice island presently known to exist in the Arctic Ocean has a mass of about 700 × 106 tonnes, an area of about 26 km2, and a mean thickness of 42.5 m. Known as Hobson’s Ice Island, this large ice feature has been tracked almost continuously since August 1983 with a succession of Argos buoys. In this paper, two particular ice-island movement episodes near the north-west coast of Axel Heiberg Island are described: 6–16 May 1986 and 14–21 June 1986. Each movement episode is analyzed in terms of the forces acting on the ice island, including wind shear, water drag, water shear, Coriolis force, sea-surface tilt, and pack-ice force. Ice-island movement is generally preceded by an offshore surface wind, and a threshold wind speed of 6 m s°1 appears to be necessary to initiate ice-island motion. An angle of 50° between surface wind and ice-island movement direction is noted during one episode. The pack-ice force, which appears to be the dominant arresting factor of ice-island motion for these two episodes, varies from 100° to 180° to the left of the ice-island velocity direction, depending upon whether the ice island is accelerating or decelerating.
Necrotising enterocolitis (NEC) is a common disease in premature infants characterised by intestinal ischaemia and necrosis. The only effective preventative strategy against NEC is the administration of breast milk, although the protective mechanisms remain unknown. We hypothesise that an abundant human milk oligosaccharide (HMO) in breast milk, 2′-fucosyllactose (2′FL), protects against NEC by enhancing intestinal mucosal blood flow, and we sought to determine the mechanisms underlying this protection. Administration of HMO-2′FL protected against NEC in neonatal wild-type mice, resulted in a decrease in pro-inflammatory markers and preserved the small intestinal mucosal architecture. These protective effects occurred via restoration of intestinal perfusion through up-regulation of the vasodilatory molecule endothelial nitric oxide synthase (eNOS), as administration of HMO-2′FL to eNOS-deficient mice or to mice that received eNOS inhibitors did not protect against NEC, and by 16S analysis HMO-2′FL affected the microbiota of the neonatal mouse gut, although these changes do not seem to be the primary mechanism of protection. Induction of eNOS by HMO-2′FL was also observed in cultured endothelial cells, providing a link between eNOS and HMO in the endothelium. These data demonstrate that HMO-2′FL protects against NEC in part through maintaining mesenteric perfusion via increased eNOS expression, and suggest that the 2′FL found in human milk may be mediating some of the protective benefits of breast milk in the clinical setting against NEC.
Based on the study of DNA adduction with nicotine, we have measured the mouse hepatic histone adduction with 14C-labeled nicotine in vivo by bio-accelerator mass spectrometry (bio-AMS). In the exposure of mice to nicotine, the dose range administered was from 0.2 μg to 6.0 μg kg b.w.-1, which was equivalent to a very low level of human exposure to cigarette smoke. The adducts of either histone 1 (H1) or histone 3 (H3) with nicotine in mouse liver increased markedly with increasing nicotine dose. Our results have demonstrated that in the study of protein adduction with toxic xenobiotics as a biomarker, the AMS method achieves the highest sensitivity, 4.6 × 10-17 mol (46 amol) adducts per mg H1 protein, compared to all the other methods used previously.