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Abstract We determined the macroscopic limit for phase synchronization of cellular clocks in an artificial tissue created by a “big chamber” microfluidic device to be about 150,000 cells or less. The dimensions of the microfluidic chamber allowed us to calculate an upper limit on the radius of a hypothesized quorum sensing signal molecule of 13.05 nm using a diffusion approximation for signal travel within the device. The use of a second microwell microfluidic device allowed the refinement of the macroscopic limit to a cell density of 2166 cells per fixed area of the device for phase synchronization. The measurement of averages over single cell trajectories in the microwell device supported a deterministic quorum sensing model identified by ensemble methods for clock phase synchronization. A strong inference framework was used to test the communication mechanism in phase synchronization of quorum sensing versus cell-to-cell contact, suggesting support for quorum sensing. Further evidence came from showing phase synchronization was density-dependent.

With both light entrainment data (L/D) and free running data in the dark (D/D), Variable Topology Ensemble Methods (VTENS) were used to reconstruct the entire genome-scale clock network involving 3380 genes and their products under the hypothesis that clock-controlled genes are both transcriptionally regulated and post-transcriptionally regulated through RNA operons. The clock network has 12 hubs with target genes surrounding twelve regulators, and 694 putative clock-controlled genes provide linkage between hubs in their joint regulation. There were 71 significant feedforward loops within this clock network, the majority of which involved genes lhp-1 and NCU06108 targeting genes connected with the ribosome and ribosome biogenesis. All 12 regulators target amino acid biosynthesis. The largest hub (768 genes) surrounded the post-transcriptional regulator lhp-1 defining an RNA operon. There appears to be no partitioning of light-regulated genes and circadian genes between the 12 hubs. The regulators lhp-1, has-1, and rrp-3 appear to target putative clock-controlled genes in ribosome biogenesis. The combined hypothesis of 6 RNA operons and 5 transcriptional regulons was successful in describing the dynamics of the clock network with 3380 genes and their products with a $\chi ^{2} =2.133$ per data point for 60,759 mRNA time points. With little known about allosteric regulation of metabolism, the clock network provided a major link between gene regulation and metabolism.

Abstract Background There are more than 300,000 hip fractures yearly in the USA with mortality rates of 20% within 1 year. The treatment of osteoporotic fractures is a major challenge as bone quality is poor, and healing is expected to delay due to the impaired healing properties with respect to bone formation, angiogenesis, and mineralization. Enhancement of osteoporotic fracture healing and function is therefore critical as a major goal in modern fracture management. Previous pre-clinical studies have shown that low-magnitude high-frequency vibration (LMHFV) accelerates osteoporotic fracture healing. The objective of this study is to investigate the effect of LMHFV on accelerating trochanteric hip fracture healing and functional recovery. Methods This is a randomized, double-blinded, placebo-controlled clinical trial to evaluate the effect of LMHFV in accelerating trochanteric hip fracture healing. All fractures undergo cephalomedullary nail fixation. The primary outcome of this study is time to fracture healing by X-ray. Computed tomography (CT) and dual-energy X-ray absorptiometry (DXA) will also be performed. Blood circulation at the fracture site will be assessed by dynamic perfusion magnetic resonance (MR). Clinical results include functional recovery by muscle strength, timed up and go test (TUG), quality of life questionnaire (SF-36), balancing, falls, and mortality. Discussion Previous animal studies have demonstrated LMHFV to improve both normal and osteoporotic fracture healing by accelerating callus formation and mineralization. The mechanical stimulation stimulates angiogenesis by significantly enhancing vascular volume and blood flow velocity. This is the first study to translate LMHFV to enhancing hip fracture healing clinically. Positive results would provide a huge impact in the recovery of hip fracture patients and save healthcare costs. Trial registration Clinicaltrials.gov NCT04063891. Registered on August 21, 2019

Abstract To determine whether state-of-the-art multi-energy spectral photon-counting computed tomography (MARS) can detect knee arthroplasty implant failure not detected by standard pre-operative imaging techniques. A total knee arthroplasty (TKA) removed from a patient was reviewed. The extracted prosthesis [NexGen Legacy Posterior Stabilized (LPS) TKA] was analyzed as were pre-operative imaging examination and compared with a MARS-CT examination obtained of the extracted TKA prosthesis. Radiographs, fluoroscopy, ultrasound and MRI preoperatively did not reveal the cause of the implant failure. MARS CT images of the extracted prosthesis clearly showed the presence of posteromedial polyethylene and tibial tray wear which is compatible with the clinical appearance of the extracted TKA. MARS can identify polyethylene insert and metallic tibial tray wear as a cause of TKA failure, that could not be identified with on standard pre-operative imaging. Although clinical MARS CT system is still under development, this case does illustrate its potential clinical usefulness. This is the first study to document how MARS CT imaging can detect orthopedic implant failure not detected by standard current imaging techniques. This system has a potential clinical application in orthopedic patients.

BackgroundDementia is the most feared disease associated with aging. Prolonged fears about memory loss and dementia can have harmful consequences even in the absence of cognitive decline. Fear of dementia is associated with poorer health outcomes and psychological well-being and increased memory failures in older adults. ObjectiveWe will conduct a randomized controlled trial to determine the feasibility of a tailored, web-based mindfulness program to reduce fear of memory loss and increase quality of life in older adults experiencing heightened fear. MethodsEighty participants will be recruited and divided into 2 groups (40 in each group). One group will receive psychoeducation plus mindfulness training. A second group will receive psychoeducation, mindfulness training, and additional modules targeting maladaptive behavioral avoidance (ie, social and cognitive withdrawal). ResultsOur recent etiological model posits that maladaptive behavioral avoidance strategies critically underlie psychosocial dysfunction associated with fear of memory loss. Thus, we predict better outcomes in the second group, including reduced fear of memory loss (primary outcome), Alzheimer disease, anxiety, and subjective memory failures, and increased quality of life (secondary outcomes). Outcome measures will be applied at 5 time points (before, baseline, interim, and after the intervention, and at 3-month follow-up). Data will be analyzed using mixed models and correlations. ConclusionsResults from this study will contribute to the current literature on dementia-related fear and improve our understanding of how to effectively address and reduce these fears. Trial RegistrationClinicalTrials.gov NCT04821960; https://clinicaltrials.gov/ct2/show/NCT04821960. International Registered Report Identifier (IRRID)PRR1-10.2196/30514

Using a microfluidics device, fluorescence of a recorder (mCherry or mVenus) gene driven by a clock-controlled gene-2 promoter (ccg-2p) was measured simultaneously on over 1000 single cells of Neurospora crassa every half hour for 10 days under each of varied light and temperature conditions. Single cells were able to entrain to light over a wide range of day lengths, including 6, 12, or 36 h days. In addition, the period of oscillations in fluorescence remained remarkably stable over a physiological range of temperatures from 20 °C to 30 °C (Q10 = 1.00-1.07). These results provide evidence of an autonomous clock in most single cells of N. crassa. While most cells had clocks, there was substantial variation between clocks as measured by their phase, raising the question of how such cellular clocks in single cells phase-synchronize to achieve circadian behavior in eukaryotic systems at the macroscopic level of 107 cells, where most measurements on the clock are performed. Single cells were placed out of phase by allowing one population to receive 6 or 12 h more light before lights out (D/D). The average phase difference was reduced in the mixed population relative to two unmixed control populations.

In the previous paper, we reconstructed the entire transcriptional network for all 2418 clockassociated genes in the model filamentous fungus, Neurospora crassa (N. crassa). Several authors have suggested that there is extensive post-transcriptional control in the genome-wide clock network (IEEE 3: 27, 2015). Here we have successfully reconstructed the entire clock network in N. crassa with a variable topology ensemble method (VTENS), assigning each clock-associated gene to the regulation of one or more of five transcription factors as well as to six RNA operons. The resulting network provides a unifying framework to explore the clock's linkage to metabolism through post-transcriptional regulation, in which ~850 genes are predicted to fall under the regulatory control of an RNA operon. A unique feature of all of the RNA operons inferred is their functional connection to genes connected to the ribosome. We have been successful in distinguishing several hypotheses about regulatory topologies of the clock network through protein profiling of the regulators.

Most genetic networks, such as that for the biological clock, are part of much larger modules controlling fundamental processes in the cell, such as metabolism, development, and response to environmental signals. For example, the biological clock is part of a much larger network controlling the circadian rhythms of about 2418 distinct genes in the genome (with 11 000 genes) of the model system, Neurospora crassa. Predicting and understanding the dynamics of all of these genes and their products in a genetic network describing how the clock functions is a challenge and beyond the current capability of the fastest serial computers. We have implemented a novel variable-topology supernet ensemble method using Markov chain Monte Carlo simulations to fit and discover a regulatory network of unknown topology composed of 2418 genes describing the entire clock circadian network, a network that is found in organisms ranging from bacteria to humans, by harnessing the power of the general-purpose graphics processing unit and exploiting the hierarchical structure of that genetic network. The result is the construction of a genetic network that explains mechanistically how the biological clock functions in the filamentous fungus N. crassa and is validated against over 31 000 data points from microarray experiments. Two transcription factors are identified targeting ribosome biogenesis in the clock network.

This study examined the test–retest and internal reliability of a scale used to measure celebrity worship. We administered the Celebrity Attitude Scale (CAS) and several related items on two different occasions approximately 3 months apart to 248 participants from three universities and one college. We hypothesized that attitudes about celebrities would remain fairly stable over time. Results confirmed the hypothesis and were discussed in relation to previous research in which the CAS was used.

An ensemble of genetic networks that describe how the model fungal system, Neurospora crassa, utilizes quinic acid (QA) as a sole carbon source has been identified previously. A genetic network for QA metabolism involves the genes, qa-1F and qa-1S, that encode a transcriptional activator and repressor, respectively and structural genes, qa-2, qa-3, qa-4, qa-x, and qa-y. By a series of 4 separate and independent, model-guided, microarray experiments a total of 50 genes are identified as QA-responsive and hypothesized to be under QA-1F control and/or the control of a second QA-responsive transcription factor (NCU03643) both in the fungal binuclear Zn(II)2Cys6 cluster family. QA-1F regulation is not sufficient to explain the quantitative variation in expression profiles of the 50 QA-responsive genes. QA-responsive genes include genes with products in 8 mutually connected metabolic pathways with 7 of them one step removed from the tricarboxylic (TCA) Cycle and with 7 of them one step removed from glycolysis: (1) starch and sucrose metabolism; (2) glycolysis/glucanogenesis; (3) TCA Cycle; (4) butanoate metabolism; (5) pyruvate metabolism; (6) aromatic amino acid and QA metabolism; (7) valine, leucine, and isoleucine degradation; and (8) transport of sugars and amino acids. Gene products both in aromatic amino acid and QA metabolism and transport show an immediate response to shift to QA, while genes with products in the remaining 7 metabolic modules generally show a delayed response to shift to QA. The additional QA-responsive cutinase transcription factor-1β (NCU03643) is found to have a delayed response to shift to QA. The series of microarray experiments are used to expand the previously identified genetic network describing the qa gene cluster to include all 50 QA-responsive genes including the second transcription factor (NCU03643). These studies illustrate new methodologies from systems biology to guide model-driven discoveries about a core metabolic network involving carbon and amino acid metabolism in N. crassa.

Mistaking psychogenic nonepileptic paroxysmal episodes (PNEPEs) for epileptic seizures (ES) is potentially dangerous, and certain features should alert physicians to a possible PNEPE diagnosis. Psychogenic nonepileptic paroxysmal episodes due to factitious seizures carry particularly high risks of morbidity or mortality from nonindicated emergency treatment and, often, high costs in wasted medical treatment expenditures. We report a case of a 28-year-old man with PNEPEs that were misdiagnosed as ES. The patient had been on four antiseizure medications (ASMs) with therapeutic serum levels and had had multiple intubations in the past for uncontrolled episodes. He had no episodes for two days of continuous video-EEG monitoring. He then disconnected his EEG cables and had an episode of generalized stiffening and cyanosis, followed by jerking and profuse bleeding from the mouth. The manifestations were unusually similar to those of ES, except that he was clearly startled by spraying water on his face, while he was stiff in all extremities and unresponsive. There were indications that he had sucked blood from his central venous catheter to expel through his mouth during his PNEPEs while consciously holding his breath. Normal video-EEG monitoring; the patient's volitional and deceptive acts to fabricate the appearance of illness, despite pain and personal endangerment; and the absence of reward other than remaining in a sick role were all consistent with a diagnosis of factitious disorder.

A model-driven discovery process, Computing Life, is used to identify an ensemble of genetic networks that describe the biological clock. A clock mechanism involving the genes white-collar-1 and white-collar-2 (wc-1 and wc-2) that encode a transcriptional activator (as well as a blue-light receptor) and an oscillator frequency (frq) that encodes a cyclin that deactivates the activator is used to guide this discovery process through three cycles of microarray experiments. Central to this discovery process is a new methodology for the rational design of a Maximally Informative Next Experiment (MINE), based on the genetic network ensemble. In each experimentation cycle, the MINE approach is used to select the most informative new experiment in order to mine for clock-controlled genes, the outputs of the clock. As much as 25% of the N. crassa transcriptome appears to be under clock-control. Clock outputs include genes with products in DNA metabolism, ribosome biogenesis in RNA metabolism, cell cycle, protein metabolism, transport, carbon metabolism, isoprenoid (including carotenoid) biosynthesis, development, and varied signaling processes. Genes under the transcription factor complex WCC ( = WC-1/WC-2) control were resolved into four classes, circadian only (612 genes), light-responsive only (396), both circadian and light-responsive (328), and neither circadian nor light-responsive (987). In each of three cycles of microarray experiments data support that wc-1 and wc-2 are auto-regulated by WCC. Among 11,000 N. crassa genes a total of 295 genes, including a large fraction of phosphatases/kinases, appear to be under the immediate control of the FRQ oscillator as validated by 4 independent microarray experiments. Ribosomal RNA processing and assembly rather than its transcription appears to be under clock control, suggesting a new mechanism for the post-transcriptional control of clock-controlled genes.

Abstract Catchment floods are more challenging due to intensive urbanization and climate change. Enlightened by the Low Impact Development (LID), China initiated the Sponge City Program (SCP) to transform Urban Flood Management (UFM) to be more environmentally friendly in 2013. The China National Government (CNG) has subsidized municipal SCP facilities to enhance urban flood resilience while delivering multiple co‐benefits for urban ecosystems and social well‐being. Recent floods at Schleiden (Germany), Arizona State (USA), and Zhengzhou (China) in 2021 reflected the necessity of Catchment Flood Management (CFM) to cover the whole catchment scale. The SCP, designed to handle small‐scale urban pluvial floods, has brought concerns when facing larger‐scale fluvial floods after the Zhengzhou 2021 flood. Indeed, catchment‐scale Natural Flood Management (NFM) can manage fluvial floods while improving flood adaptations sustainably from upstream to downstream reaches. This research develops a new framework named the Sponge Catchment Management Plan (SCMP), including structural and Nonstructural elements. On the structural side, the SCMP framework integrates NFM with the SCP and Grey Engineering (GE) for reducing the fluvial flood discharge peaks in the whole‐catchment scale. On the nonstructural side, the SCMP encourages collaborative governance, revising technical standards, and improving “bottom‐up” participation. This research used Semi‐Structured Interviews (SSIs) and a Focus Group Approach (FGA) to explore 62 professional and Nonprofessional stakeholders’ perspectives on the SCMP framework. Some professional respondents did not know much about the NFM and were worried about the effectiveness of this practice. But most interviewees supported the SCMP pilot work and shared the co‐benefits from the NFM. This case study at the SW China, Guiyang, could be a lesson to encourage other Chinese cities further implement SCP to improve catchment‐scale flood resilience.

Abstract Pest animal populations, such as rodents, often irrupt in response to pulsed resources. However, few studies have considered how understanding the propagation of irruptions across landscapes could lead to more efficient pest suppression. Resource pulses might create temporary source–sink dynamics in heterogeneous environments, whereby reservoirs of animals living in high‐quality habitat increase and spill over into more marginal habitat. Low‐density populations in marginal habitat could also increase through in situ breeding by residents in response to increased food availability. Understanding the relative importance of these two nonmutually exclusive processes is important as pest outbreaks could potentially be more efficiently controlled by targeting source populations early in an outbreak. We used a Bayesian hierarchical model to estimate the importance of density‐dependent emigration from lower elevation habitats versus in situ breeding by resident animals to the population growth of invasive ship rats (Rattus rattus) in marginal, high elevation habitats during a pulsed resource event (beech seed mast). We found that emigration from lower elevations was important for facilitating rapid population growth at high elevations, enabling rats to reach peak densities of 10.6 rats ha−1. Without immigration, rats were predicted to reach peak densities of only 1.8 rats ha−1 at high elevation, given their densities in that habitat when we started monitoring (0.6 rats ha−1). This result suggests that rat control that targets low and mid‐elevations only may be sufficient to suppress irruptions in high‐elevation habitat if control effectively prevents immigration. Our study suggests spillover from higher quality habitats may enable outbreaks to rapidly propagate over landscapes. However, for r‐selected taxa such as rodents, even very low densities of animals living in marginal habitats can increase significantly when resource pulses occur, albeit at lower densities than for populations in higher quality habitat.

Hydrological modeling for landscape and catchment scale applications requires upscaling of soil hydraulic parameters which are generally only available at point scale. We present a case study where hourly root zone soil water content and drainage observations from nine flat, pastoral sites (Waikato and Canterbury regions in New Zealand) were used to develop an upscaling approach to parameterize the soil water balance module of the TopNet catchment model, based on scaling multi-layer soil profile information from the national soil data base, S-map, to the single-layer soil profile used in TopNet. Using a Bayesian calibration approach, the hydraulic behavioral parameters of TopNet's soil water balance module were identified. Of the eleven calibration parameters considered three were found to be insensitive to data (stress point, unsaturated hydraulic conductivity and infiltration rate); three were correlated and could be determined from specific soil water content observations (wilting point, field capacity and drainable water); and five were correlated and could be determined from combined specific soil water content and drainage observations (drainage rate, saturated hydraulic conductivity profile, effective soil depth, soil water holding capacity and wetting front suction). Based on the eight correlated parameters, upscaling functions were then developed to derive suitable model parameters from S-map-hydro for each site. The validity of the upscaling functions was verified at each site. The approach used in this research can be used to parameterize the TopNet model at other similar locations, and also provides a transferable framework to parameterize other catchment-scale hydrology models where point-scale soil hydraulic data available.

Rapid urbanization has sharply increased the pressure of urban water issues (e.g., urban flooding and water pollution) in the Chinese megacities during last three decades. Sustainable urban water management approaches, such as Nature Based Solutions (NBS) and Low Impact Developments (LIDs), have successfully delivered long-term benefits to cities in Europe and North America. Similarly, the Chinese Sponge City Program (SCP) initiated in 2013 and experimented in 30 pilot Chinese cities. This paper reviewed the first stage of the SCP from 2015 to 2020 by using observation, Semi-Structured Interview (SSI) and Focus Group Approach (FGA) in context of Gui'an New Distinct, SW China to investigate the SCP progress and issues: (1). whether it is effectively solving urban water issues; (2). if there are any major challenges and barriers in the SCP practice. The findings of this case study provide potential solutions for improving the SCP and sustainable urban water management and possibly transform to other Sponge Cities in China.

Early warnings decision support systems are recognized as effective soft adaptation tools to prepare for the impacts of imminent flooding and minimize potential injuries and/or loss of life in flood-prone regions. This paper presents a case study of a pilot project that aimed to establish an impacts-based flood monitoring, early warnings, and decision support system for the Vaisigano River which flows through Apia, the capital of Samoa. This river is located in a characteristic short and steep catchment with rapid critical flood peak durations following periods of intense rainfall. The developed system integrates numerical weather prediction rainfall forecasts, real-time rainfall, river level and flow monitoring data, precomputed rainfall-runoff simulations, and flood inundation estimates of exposure levels and threat to human safety at buildings and on roads for different return period events. Information is ingested into a centralized real-time, web-based, flood decision support system portal that enables hydrometeorological officers to monitor, forecast and alert relevant emergency or humanitarian responders of imminent flooding with adequate lead time. This includes nowcasts and forecasts of estimated flood peak time, magnitude and likely impacts of inundation. The occurrence of three distinct extreme rainfall and flood events over the 2020/2021 tropical cyclone season provided a means to operationally test the system. In each case, the system proved adequate in alerting duty officers of imminent flooding in the Vaisigano catchment with up to 24 h warnings and response lead time. Gaps for improvement of system capabilities and performance are discussed, with recommendations for future work suggested.

Flood management is a complex issue in Chinese cities that exhibit high populations and have undergone rapid urbanization. Urban flood management (UFM) approaches can be used to mitigate urban flood risk. To address urban issues of poor water quality and urban surface flooding, the Sponge City Program (SCP) was initiated in 2013 in China. The SCP aims to provide an opportunity for Chinese cities to improve their current UFM practices. This study looks at Guiyang (a pilot sponge city located in SW China) as a case study to identify the challenges and opportunities of UFM in China. Guiyang is a valley city surrounded by a hilly landscape. Using interview records and flood data, we illustrate that the primary type of flood in Guiyang is fluvial rather than surface water flooding. In Guiyang, the current function and targets of the SCP have yet to engage with the catchment level flood management, instead mainly focusing on the site-specific context (i.e., community level). Catchment flood management planning (CFMP) and natural flood management (NFM) both address this problem and may be a more suitable approach to manage flood discharge from the upper and middle catchments in Guiyang. In addition, it is suggested that a mixed option combining “hard” infrastructure (e.g., reservoirs and floodwalls) with “soft” flood management measures (e.g., improving people awareness and participation) may improve urban flood resilience in Chinese cities.

Abstract  Increased polyamine synthesis has been associated with proliferation and progression of breast cancer, and thus, is a potential target for anticancer therapy. Polyamine depletion by α-difluoromethylornithine (DFMO) has been shown to decrease pulmonary and bone metastasis from human breast cancer cell xenografts. Following these observations, this study was designed to test the effects of DFMO on in vitro and in vivo features of the highly invasive and metastatic 4T1 murine mammary cancer cells. DFMO inhibited proliferation, caused G1-S arrest, and suppressed in vitro invasiveness of 4T1 cells. In contrast to our previous findings with MDA-MB-435 cells, DFMO did not affect the activation of signal transducers and activator of transcription 3, c-Jun N-terminal kinase, and extracellular signal-regulated kinase, but decreased phosphorylation of p38. DFMO did not alter the expression of Twist. DFMO delayed the orthotopic growth of 4T1 xenografts in association with suppressed putrescine and spermidine levels but increased levels of spermine. DFMO did not affect pulmonary metastasis when primary tumors of control and DFMO-treated mice were matched for size. Interestingly, DFMO reduced Ki-67 expression only in the primary tumors but did not affect its expression in the metastatic tumors in the lung. Cleaved caspase-3 expression was not affected by DFMO in either the primary tumors or the pulmonary metastasis. In summary, DFMO treatment markedly inhibited in vitro proliferation and invasiveness of 4T1 cells and retarded the growth of orthotopic xenografts in mice. The failure of DFMO to inhibit pulmonary metastasis in this system appears to be due, at least in part, to its lack of antiproliferative effect at the metastatic sites. [ABSTRACT FROM AUTHOR]

Abstract  Increased polyamine synthesis has been associated with proliferation and progression of breast cancer, and thus, is a potential target for anti-cancer therapy. Polyamine depletion by DFMO has been shown to decrease pulmonary and bone metastasis from human breast cancer cell xenografts. Following these observations, this study was designed to test the effects of DFMO on in vitro and in vivo features of the highly invasive and metastatic 4T1 murine mammary cancer cells. DFMO inhibited proliferation, caused G1-S arrest, and suppressed in vitro invasiveness of 4T1 cells. In contrast to our previous findings with MDA-MB-435 cells, DFMO did not affect the activation of STAT3, JNK, and ERK, but decreased phosphorylation of p38. DFMO did not alter the expression of Twist. DFMO delayed the orthotopic growth of 4T1 xenografts in association with suppressed putrescine and spermidine levels but increased levels of spermine. DFMO did not affect pulmonary metastasis when primary tumors of control and DFMO-treated mice were matched for size. Interestingly, DFMO reduced Ki-67 expression only in the primary tumors but did not affect its expression in the metastatic tumors in the lung. Cleaved caspase-3 expression was not affected by DFMO in either the primary tumors or pulmonary metastasis. In summary, DFMO treatment markedly inhibited in vitro proliferation and invasiveness of 4T1 cells and retarded the growth of orthotopic xenografts in mice. The failure of DFMO to inhibit pulmonary metastasis in this system appears to be due, at least in part, to its lack of anti-proliferative effect at the metastatic sites. [ABSTRACT FROM AUTHOR]

Abstract Background Ultrasound-guided peripheral intravenous access may present an alternative to central or intraosseous access in patients with difficult peripheral veins. Using venepuncture of a phantom model as a proxy, we investigated whether novice ultrasound users should adopt a cross-sectional or longitudinal approach when learning to access peripheral veins under ultrasound guidance. This result would inform the development of a structured training method for this procedure. Methods We conducted a randomised controlled trial of 30 medical students. Subjects received 35 min of training, then attempted to aspirate 1 ml of synthetic blood from a deep vein in a training model under ultrasound guidance. Subjects attempted both the cross-sectional and longitudinal approaches. Group 1 used cross-sectional first, followed by longitudinal. Group 2 used longitudinal first, then cross-sectional. We measured the time from first puncture of the model’s skin to aspiration of fluid, and the number of attempts required. Subjects also reported difficulty ratings for each approach. Paired sample t-tests were used for statistical analysis. Results The mean number of attempts was 1.13 using the cross-sectional approach, compared with 1.30 using the longitudinal approach (p = 0.17). Mean time to aspiration of fluid was 45.1 s using the cross-sectional approach and 52.8 s using the longitudinal approach (p = 0.43). The mean difficulty score out of 10 was 3.97 for the cross-sectional approach and 3.93 for the longitudinal approach (p = 0.95). Conclusions We found no significant difference in effectiveness between the cross-sectional and longitudinal approaches to ultrasound-guided venepuncture when performed on a model. We believe that both approaches should be included when teaching ultrasound-guided peripheral vascular access. To confirm which approach would be best in clinical practice, we advocate future testing of both approaches on patients.

Strategies to increase parent involvement and its beneficial effects, in particular, among parents whose children traditionally have low academic achievement, abound in the educational literature. Yet, conspicuously absent is an empirical examination of the relation of principal behaviors on parent involvement. The present study analyzed survey data from principals regarding their behaviors and the relation of their behavior to survey data from parents regarding involvement in their children’s education. Among schools having higher concentrations of socioeconomically-disadvantaged and non-English-speaking students, the roles of master teacher and missionary were associated with higher levels of parent involvement and the role of the gamesman with lower levels of parent involvement. Results suggest that the effectiveness of principal roles is dependent on the needs and life circumstances of socioeconomically-disadvantaged school populations. [ABSTRACT FROM AUTHOR]

Using Takahashi & Fox (2005) as an exemplar, this paper argues that analyses of English ellipsis that make recourse to a MaxElide constraint (or a theoretical reduction thereof) are misguided, and that one must look past MaxElide to explain the distribution of acceptability in the elliptical rebinding constructions that MaxElide was originally invoked to explain. A novel analysis is outlined which attributes the unacceptability observed in the rebinding dataset to an inability to satisfy a more restrictive, reflexive version of Takahashi & Fox's (ibid.) Parallelism condition on ellipsis recoverability.

This paper argues that the meaning of a clausal ellipsis site can only be recovered from a syntactically derived question, regardless of whether this question is explicitly uttered or is merely pragmatically inferred. This entails that the meaning of a clausal ellipsis site cannot be recovered from an inferred question q in a language L if q is syntactically ill-formed in L. I demonstrate that this restriction on recoverability can account for Merchant’s (2001; 2004) Preposition-Stranding Generalisation and for the observation that fragments appear to be sensitive to syntactic islands (Merchant 2004; Abels 2011; Barros et al. 2014; 2015) without any mention of whether remnants of clausal ellipsis themselves undergo movement. Because there is no need to stipulate that remnants themselves undergo (often exceptional) movement under this approach, a theory of clausal ellipsis modelled on Cable’s (2010) Q-based analysis of wh-questions is developed that permits non-pronunciation “around” designated phrases. This approach is shown to be preferred on many occasions to the predominant movement-based analysis (Merchant 2004), which is too restrictive and must frequently resort to the notion of ellipsis repair.

Background: Infections acquired in hospital are an important cause of morbidity and mortality in very preterm infants. Several small trials have suggested that supplementing the enteral diet of very preterm infants with lactoferrin, an antimicrobial protein processed from cow’s milk, prevents infections and associated complications. Objective: To determine whether or not enteral supplementation with bovine lactoferrin (The Tatua Cooperative Dairy Company Ltd, Morrinsville, New Zealand) reduces the risk of late-onset infection (acquired > 72 hours after birth) and other morbidity and mortality in very preterm infants. Design: Randomised, placebo-controlled, parallel-group trial. Randomisation was via a web-based portal and used an algorithm that minimised for recruitment site, weeks of gestation, sex and single versus multiple births. Setting: UK neonatal units between May 2014 and September 2017. Participants: Infants born at

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We report on a comparative study of the low temperature emission and polarisation properties of InGaN/GaN quantum wells grown on nonpolar ($ 11\bar{2}0 $) a-plane and ($ 10\bar{1}0 $) m-plane free-standing bulk GaN substrates where the In content varied from 0.14 to 0.28 in the m-plane series and 0.08 to 0.21 for the a-plane series. The low temperature photoluminescence spectra from both sets of samples are broad with full width at half maximum height increasing from 81 to 330 meV as the In fraction increases. Photoluminescence excitation spectroscopy indicates that the recombination mainly involves strongly localised carriers. At 10 K the degree of linear polarisation of the a-plane samples is much smaller than of the m-plane counterparts and also varies across the spectrum. From polarisation-resolved photoluminescence excitation spectroscopy we measured the energy splitting between the lowest valence sub-bands to lie in the range of 23–54 meV for the a- and m-plane samples in which we could observe distinct exciton features. Thus the thermal occupation of a higher valence sub-band cannot be responsible for the reduction of the degree of linear polarisation at 10 K. Time-resolved spectroscopy indicates that in a-plane samples there is an extra emission component which is at least partly responsible for the reduction in the degree of linear polarisation.

Urban flooding has become a serious issue in most Chinese cities due to rapid urbanization and extreme weather, as evidenced by severe events in Beijing (2012), Ningbo (2013), Guangzhou (2015), Wuhan (2016), Shenzhen (2019), and Chongqing (2020). The Chinese “Sponge City Program” (SCP), initiated in 2013 and adopted by 30 pilot cities, is developing solutions to manage urban flood risk, purify stormwater, and provide water storage opportunities for future usage. Emerging challenges to the continued implementation of Sponge Cities include (1) uncertainty regarding future hydrological conditions related to climate change projections, which complicates urban planning and designing infrastructure that will be fit for purpose over its intended operating life, and (2) the competing priorities of stakeholders and their reluctance to make trade-offs, which obstruct future investment in the SCP. Nature-Based Solutions (NBS) is an umbrella concept that emerged from Europe, which encourages the holistic idea of considering wider options that combine “Blue–Green” practices with traditional engineering to deliver “integrated systems of Blue–Green–Grey infrastructure”. NBS includes interventions making use of natural processes and ecosystem services for functional purposes, and this could help to improve current pilot SCP practices. This manuscript reviews the development of the SCP, focusing on its construction and design aspects, and discusses how approaches using NBS could be included in the SCP to tackle not only urban water challenges but also a wide range of social and environmental challenges, including human health, pollution (via nutrients, metals, sediments, plastics, etc.), flood risk, and biodiversity.

This paper describes USP-NF compendial updates to six ‘high-priority” excipient monographs: Glycerin, Propylene Glycol, Sorbitol Solution, Sorbitol Sorbitan Solution, Noncrystallizing Sorbitol Solution and Maltitol Solution. The USP-NF revisions arose from the Food and Drug Administration’s (FDA’s) requests to include, as part of each monograph’s Identification test, a limit test to detect the presence of Diethylene Glycol (DEG), a toxic adulterant. These revisions align with the 2007 FDA Guidance for Industry: Testing of Glycerin for Diethylene Glycol (1), that drug product manufacturers perform a specific identity test for DEG on all containers of all lots of glycerin before glycerin is used in the manufacture and preparation of drug products. This paper describes several risk factors due to a complex global excipient supply chain, nonspecific specifications, inadequate supply chain qualification, and poor understanding of regulations. Strengthening and conformance to compendial specifications is one of the tools necessary to mitigate risk and help prevent the next DEG adulteration that is part of USP’s efforts to ensure safe medicines.

This paper describes USP-NF compendial updates to six ‘high-priority” excipient monographs: Glycerin, Propylene Glycol, Sorbitol Solution, Sorbitol Sorbitan Solution, Noncrystallizing Sorbitol Solution and Maltitol Solution. The USP-NF revisions arose from the Food and Drug Administration’s (FDA’s) requests to include, as part of each monograph’s Identification test, a limit test to detect the presence of Diethylene Glycol (DEG), a toxic adulterant. These revisions align with the 2007 FDA Guidance for Industry: Testing of Glycerin for Diethylene Glycol (1), that drug product manufacturers perform a specific identity test for DEG on all containers of all lots of glycerin before glycerin is used in the manufacture and preparation of drug products. This paper describes several risk factors due to a complex global excipient supply chain, nonspecific specifications, inadequate supply chain qualification, and poor understanding of regulations. Strengthening and conformance to compendial specifications is one of the tools necessary to mitigate risk and help prevent the next DEG adulteration that is part of USP’s efforts to ensure safe medicines.