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This paper extends a previous study of free-surface flow over two localised obstacles using the framework of the forced Korteweg–de Vries equation, to an analogous study of flow over two localised holes, or a combination of an obstacle and a hole. Importantly the terminology obstacle or hole can be reversed for a stratified fluid and refers more precisely to the relative polarity of the forcing and the solitary wave solution of the unforced Korteweg–de Vries equation. As in the previous study, our main concern is with the transcritical regime when the oncoming flow has a Froude number close to unity. In the transcritical regime at early times, undular bores are produced upstream and downstream of each forcing site. We then describe the interaction of these undular bores between the forcing sites, and the outcome at very large times.
A new fossil site in a previously unexplored part of western Madagascar (the Beanka Protected Area) has yielded remains of many recently extinct vertebrates, including giant lemurs (Babakotia radofilai, Palaeopropithecus kelyus, Pachylemur sp., and Archaeolemur edwardsi), carnivores (Cryptoprocta spelea), the aardvark-like Plesiorycteropus sp., and giant ground cuckoos (Coua). Many of these represent considerable range extensions. Extant species that were extirpated from the region (e.g., Prolemur simus) are also present. Calibrated radiocarbon ages for 10 bones from extinct primates span the last three millennia. The largely undisturbed taphonomy of bone deposits supports the interpretation that many specimens fell in from a rock ledge above the entrance. Some primates and other mammals may have been prey items of avian predators, but human predation is also evident. Strontium isotope ratios (87Sr/86Sr) suggest that fossils were local to the area. Pottery sherds and bones of extinct and extant vertebrates with cut and chop marks indicate human activity in previous centuries. Scarcity of charcoal and human artifacts suggests only occasional visitation to the site by humans. The fossil assemblage from this site is unusual in that, while it contains many sloth lemurs, it lacks ratites, hippopotami, and crocodiles typical of nearly all other Holocene subfossil sites on Madagascar.
Sintered tape-cast yttria-stabilized zirconia (YSZ) was evaluated for its elemental composition, crystal structure, and imaged with atomic force microscopy (AFM) and scanning electron microscopy (SEM). Human bone marrow stem cells (hBMSC) were cultured on the ceramic and differentiated into the osteoblast lineage; alkaline phosphatase (ALP) activity was tracked as a differentiation marker. The YSZ was composed of purely tetragonal grains with a median equivalent circular diameter of 283 nm. Zirconium, yttrium, oxygen, and adventitious carbon was detected on the substrate with no other elements in significant quantities detected. YSZ samples had an RMS roughness value of 27 nm, elastic modulus of 206 ± 14 GPa, and hardness of 14 ± 2 GPa. hBMSC were observed to attach and proliferate on the YSZ surfaces and had significantly increased ALP versus the undifferentiated control cultured on glass. This method for producing a YSZ ceramic yields a typical material of this type and supports attachment and differentiation of hBMSC; thus, making it useful as a bone implant material.
The rocky shores of the north-east Atlantic have been long studied. Our focus is from Gibraltar to Norway plus the Azores and Iceland. Phylogeographic processes shape biogeographic patterns of biodiversity. Long-term and broadscale studies have shown the responses of biota to past climate fluctuations and more recent anthropogenic climate change. Inter- and intra-specific species interactions along sharp local environmental gradients shape distributions and community structure and hence ecosystem functioning. Shifts in domination by fucoids in shelter to barnacles/mussels in exposure are mediated by grazing by patellid limpets. Further south fucoids become increasingly rare, with species disappearing or restricted to estuarine refuges, caused by greater desiccation and grazing pressure. Mesoscale processes influence bottom-up nutrient forcing and larval supply, hence affecting species abundance and distribution, and can be proximate factors setting range edges (e.g., the English Channel, the Iberian Peninsula). Impacts of invasive non-native species are reviewed. Knowledge gaps such as the work on rockpools and host–parasite dynamics are also outlined.
Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.
Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.
Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.
The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.
Depictions of eye images and messages encouraging compliance with social norms have successfully motivated behavioral change in a variety of experimental and applied settings. We studied the effect of these 2 visual cues on hand hygiene adherence in a cohort of hospital-based healthcare providers participating in an electronic monitoring and feedback program.
Prospective, quasi-experimental study utilizing an interrupted time-series design. Intervention placards depicting an image of eyes, a social norms message, or a control placard were placed near soap and alcohol-based hand-rub dispensers on 2 hospital units. Placards were alternated every 10 days. Hand hygiene opportunities and adherence rates were assessed electronically via the CenTrak Hand Hygiene Compliance Solution.
A total of 166 nurses and certified nursing assistants (74 on a medical-surgical unit and 92 on a progressive care unit) were monitored electronically over the 4-month study period. In total, 184,172 electronic observations were collected (110,903 on a medical-surgical unit and 73,269 on a progressive care unit). The median daily number of electronic observations was 1,471 (interquartile range, 1,337–1,584). The preintervention baseline hand hygiene adherence rate was 70%. No statistically significant increase in hand hygiene adherence was observed as a result of either intervention.
Displaying eye images or a social norms message in the hospital environment did not result in measurable improvements in HH adherence in a cohort of healthcare providers participating in an electronic monitoring and feedback program.
CVD and associated metabolic diseases are linked to chronic inflammation, which can be modified by diet. The objective of the present study was to determine whether there is a difference in inflammatory markers, blood metabolic and lipid panels and lymphocyte gene expression in response to a high-fat dairy food challenge with or without milk fat globule membrane (MFGM). Participants consumed a dairy product-based meal containing whipping cream (WC) high in saturated fat with or without the addition of MFGM, following a 12 h fasting blood draw. Inflammatory markers including IL-6 and C-reactive protein, lipid and metabolic panels and lymphocyte gene expression fold changes were measured using multiplex assays, clinical laboratory services and TaqMan real-time RT-PCR, respectively. Fold changes in gene expression were determined using the Pfaffl method. Response variables were converted into incremental AUC, tested for differences, and corrected for multiple comparisons. The postprandial insulin response was significantly lower following the meal containing MFGM (P < 0·01). The gene encoding soluble epoxide hydrolase (EPHX2) was shown to be more up-regulated in the absence of MFGM (P = 0·009). Secondary analyses showed that participants with higher baseline cholesterol:HDL-cholesterol ratio (Chol:HDL) had a greater reduction in gene expression of cluster of differentiation 14 (CD14) and lymphotoxin β receptor (LTBR) with the WC+MFGM meal. The protein and lipid composition of MFGM is thought to be anti-inflammatory. These exploratory analyses suggest that addition of MFGM to a high-saturated fat meal modifies postprandial insulin response and offers a protective role for those individuals with higher baseline Chol:HDL.
This article summarizes the results of controlled experiments in which flaked-stone points that varied in impact strength by a factor of almost three were shot at media that were increasingly inelastic and therefore likely to break the points. Broken tips were reworked if possible, and used again under the same conditions. Our results show that all damage to low impact-strength materials, especially obsidian, was generally catastrophic, and, consequently, these points could only rarely be reworked. The fact that low-strength stones were commonly used to make small arrowpoints suggests that reworking was not a primary concern for their designers. Furthermore, in those instances when broken tips could be reworked, their performance declined. In addition, reworking broken points also resulted in shapes that are uncommon in many arrowpoint assemblages. Our results suggest that the original design attributes of arrowpoints may have been less affected by reworking, and, consequently, may more accurately suggest temporal and behavioral associations.
Perceptual dimensions underlying timbre and sound-source identification have received considerable scientific attention. While these scholarly insights help us in understanding the nature of sound within a multidimensional timbral space, they carry little meaning for the majority of musicians. To help address this, we conducted two experiments to establish listeners’ perceptual thresholds (PT) for changes in sound using a staircase-procedure. Unlike most timbre perception research, these changes were sonic manipulations that are common in synthesisers, audio processors and instruments familiar to musicians and producers, and occurred within continuous sounds (rather than between discrete pairs of sounds). In experiment 1, two sounds (variants of a sawtooth oscillation) both with the same fundamental frequency (F1: 80 Hz, 240 Hz or 600 Hz) were played with no intervening gap. In each trial, the two sounds’ partials differed in amplitudes or frequencies to produce a timbre change. The sonic manipulations were varied in size to detect thresholds for the perceived timbre change – listeners were instructed to indicate whether or not they perceived a change within the sound. In experiment 2, we modified stimulus presentation to introduce the factor of transition time (TT). Rather than occurring instantaneously (as in experiment 1), the timbre manipulations were introduced gradually over the course of a 100 ms or a 1000 ms TT. Results revealed that PTs were significantly affected by the manipulations in experiment 1, and additionally by TT in experiment 2. Importantly, the data revealed an interaction between the F1 and the timbre manipulations, such that there were differential effects of timbre changes on the perceptual system depending on pitch height. Musicians (n=11) showed significantly smaller PTs compared to non-musicians (n=10). However, PTs for musicians and non-musicians were highly correlated (r=.83) across different sonic manipulations, indicating similar perceptual patterns in both. We hope that by establishing PTs for commonly used timbre manipulations, we can provide musicians with a general perceptual unit, for each manipulation, that can guide music composition and assessment.
The need for hollow microneedle arrays is important for both drug delivery and wearable sensor applications; however, their fabrication poses many challenges. Hollow metal microneedle arrays residing on a flexible metal foil substrate were created by combining additive manufacturing, micromolding, and electroplating approaches in a process we refer to as electromolding. A solid microneedle with inward facing ledge was fabricated with a two photon polymerization (2PP) system utilizing laser direct write (LDW) and then molded with polydimethylsiloxane. These molds were then coated with a seed layer of Ti/Au and subsequently electroplated with pulsed deposition to create hollow microneedles. An inward facing ledge provided a physical blocking platform to restrict deposition of the metal seed layer for creation of the microneedle bore. Various ledge sizes were tested and showed that the resulting seed layer void could be controlled via the ledge length. Mechanical properties of the PDMS mold was adjusted via the precursor ratio to create a more ductile mold that eliminated tip damage to the microneedles upon removal from the molds. Master structures were capable of being molded numerous times and molds were able to be reused. SEM/EDX analysis showed that trace amounts of the PDMS mold were transferred to the metal microneedle upon removal. The microneedle substrate showed a degree of flexibility that withstood over 100 cycles of bending from side to side without damaging. Microneedles were tested for their fracture strength and were capable of puncturing porcine skin and injecting a dye.
OBJECTIVES/SPECIFIC AIMS: The goals of this study were (1) to evaluate the effect of proarrhythmic drugs on calcium transient and (2) to use three-dimensional human engineered cardiac tissue (hECT) technology to evaluate cardiac contractile properties in response to pharmacological challenge with proarrhythmic drugs. METHODS/STUDY POPULATION: Calcium transient was measured in subject-specific iPSC-CMs by using the IonOptix system in Sotalol treated vs. untreated conditions. We fabricated human engineered cardiac tissues (hECT) in a custom designed bioreactor using low- and high-sentitive subject-specific iPSC-CMs. Contractile function of the hECT was evaluated at baseline and after Sotalol [300 µM] administration. The change in beat rate was recorded under spontaneous beating conditions; changes in other twitch parameters, including time to relaxation, were recorded under electrical stimulation. Time to relaxation served as an indicator of action potential duration (APD), which has a temporal correlation with the QT interval. RESULTS/ANTICIPATED RESULTS: The low-sensitive iPSC-CM showed a considerable drop in overall peak height of the calcium transient, in the presence of 100 µM Sotalol. The high-sensitive line, however, showed a more pronounced drop in peak height. Sotalol treatment also induced a more pronounced increase in the exponential decay time constant (tau) in the high-sensitive line compared to the low-sensitive line. The hECT fabricated with high sensitive hiPSC-CM showed a larger decrease in spontaneous beat rate in response to Sotalol (0.41 vs 0.23 fold decrease), with a higher increase in time to relaxation (1.8 vs 1.3 fold increase), compared to hECT from low sensitive hiPSC-CM. Moreover, while the low-sensitive hECT showed a positive correlation between time to relaxation and developed force, as expected after Sotalol stimulation; the high-sensitive hECT failed to show a positive inotropic response. DISCUSSION/SIGNIFICANCE OF IMPACT: Our findings suggest subject-specific iPSC-CMs and hECT, can be used to model functional abnormalities observed in diLQTS in response to Sotalol, and offer novel insights into human-based screening assays for toxic drug reactions. Success of this study may help identify key components underlying diLQT susceptibility to ultimately develop novel therapeutic agents.
Syndromic surveillance is a form of surveillance that generates information for public health action by collecting, analysing and interpreting routine health-related data on symptoms and clinical signs reported by patients and clinicians rather than being based on microbiologically or clinically confirmed cases. In England, a suite of national real-time syndromic surveillance systems (SSS) have been developed over the last 20 years, utilising data from a variety of health care settings (a telehealth triage system, general practice and emergency departments). The real-time systems in England have been used for early detection (e.g. seasonal influenza), for situational awareness (e.g. describing the size and demographics of the impact of a heatwave) and for reassurance of lack of impact on population health of mass gatherings (e.g. the London 2012 Olympic and Paralympic Games).We highlight the lessons learnt from running SSS, for nearly two decades, and propose questions and issues still to be addressed. We feel that syndromic surveillance is an example of the use of ‘big data’, but contend that the focus for sustainable and useful systems should be on the added value of such systems and the importance of people working together to maximise the value for the public health of syndromic surveillance services.
To characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition.
In a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15–28 weeks) and third trimester (28–39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes.
Women were recruited from twelve US sites (2009–2013).
Non-obese women with singleton pregnancies (n 2334).
A higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (−0·57 to −0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (−0·05 to 0·06 mm per week).
The rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.
Interoceptive deficits (ID) have been associated with non-suicidal self-injury (NSSI) and suicidal behavior in multiple studies. Many of these studies are limited in scope, and have not fully examined possible mechanisms explaining how ID affect suicidal behavior.
This study assesses how self-reported ID relate to suicide ideation and attempts in six distinct and geographically diverse samples of adults (n = 2706) and one sample of adolescents (n = 436). Participants responded to a variety of self-report questionnaires and interviews.
Contrary to our hypothesis, self-reported ID were only associated with suicidal ideation in two samples, one of which was the adolescent sample. Largely consistent with our predictions, self-reported ID exhibited an indirect effect on suicide attempts through versatility of NSSI in four of the five adult samples tested. Finally, the indirect effects of self-reported ID on suicide attempts through NSSI versatility did not act indirectly through behaviorally assessed pain tolerance.
We found that, in adults, self-reported ID are not associated with suicidal ideation, but are connected with a history of suicide attempts, through an indirect effect via NSSI. Our findings also indicate that the mechanism of action leading from self-reported ID to suicidal behavior may differ between adolescents and adults, and relate to suicidal behavior independent of pain tolerance. Clinical implications and future directions are discussed.