Freshwater invertebrate responses to fine sediment stress: A multi-continent perspective.

Excessive fine sediment (particles <2 mm) deposition in freshwater systems is a pervasive stressor worldwide. However, understanding of ecological response to excess fine sediment in river systems at the global scale is limited. Here, we aim to address whether there is a consistent response to increasing levels of deposited fine sediment by freshwater invertebrates across multiple geographic regions (Australia, Brazil, New Zealand and the UK). Results indicate ecological responses are not globally consistent and are instead dependent on both the region and the facet of invertebrate diversity considered, that is, taxonomic or functional trait structure. Invertebrate communities of Australia were most sensitive to deposited fine sediment, with the greatest rate of change in communities occurring when fine sediment cover was low (below 25% of the reach). Communities in the UK displayed a greater tolerance with most compositional change occurring between 30% and 60% cover. In both New Zealand and Brazil, which included the most heavily sedimented sampled streams, the communities were more tolerant or demonstrated ambiguous responses, likely due to historic environmental filtering of invertebrate communities. We conclude that ecological responses to fine sediment are not generalisable globally and are dependent on landscape filters with regional context and historic land management playing important roles.

The preterm infant-parent programme for attachment-PIPPA Study: a randomised controlled trial.

BACKGROUND: There is increasing recognition of adverse mental health consequences of preterm birth and the impact on social-emotional development. However, the quality of the developing parent-infant relationship may be protective, with enhanced maternal sensitivity to infants' cues associated with improved outcomes. METHODS: Eighty mothers and their preterm infants born <32 weeks gestation were randomised to intervention and standard care groups. Intervention comprised reflective interview, observation of infant cues and video interaction guidance (VIG). The primary outcome, maternal sensitivity during play, was measured by the Child Adult Relationship Evaluation-Index. Secondary outcomes were infant social-emotional problems measured by the Ages and Stages Questionnaire-Social-Emotional version. RESULTS: There was no statistically significant difference between the intervention and standard care groups in maternal sensitivity during play at 9 months corrected age (CA). In the secondary outcome analysis at 12 months CA, infants in the intervention group had fewer self-regulation problems than infants whose mothers received standard care. Per-protocol analysis revealed that infants whose mothers completed VIG had significantly fewer communication problems. CONCLUSIONS: This early attachment-focussed intervention integrating VIG for mothers and their preterm infants did not enhance maternal sensitivity; however, there were effects on infant social-emotional problems at 12 months CA. IMPACT: Preterm birth can adversely affect infant and parent mental health and the quality of the parent-infant relationship. Early intervention to support parent-infant interaction can have positive effects on infant social-emotional development. There was no statistically significant difference in maternal sensitivity during play at 9 months CA. However, there were fewer infant self-regulation and communication problems reported by mothers at 12 months CA following intervention. Further evaluations of attachment-focussed interventions in the neonatal intensive care unit are needed.

Trait-based ecology at large scales: Assessing functional trait correlations, phylogenetic constraints and spatial variability using open data.

The growing use of functional traits in ecological research has brought new insights into biodiversity responses to global environmental change. However, further progress depends on overcoming three major challenges involving (a) statistical correlations between traits, (b) phylogenetic constraints on the combination of traits possessed by any single species, and (c) spatial effects on trait structure and trait-environment relationships. Here, we introduce a new framework for quantifying trait correlations, phylogenetic constraints and spatial variability at large scales by combining openly available species' trait, occurrence and phylogenetic data with gridded, high-resolution environmental layers and computational modelling. Our approach is suitable for use among a wide range of taxonomic groups inhabiting terrestrial, marine and freshwater habitats. We demonstrate its application using freshwater macroinvertebrate data from 35 countries in Europe. We identified a subset of available macroinvertebrate traits, corresponding to a life-history model with axes of resistance, resilience and resource use, as relatively unaffected by correlations and phylogenetic constraints. Trait structure responded more consistently to environmental variation than taxonomic structure, regardless of location. A re-analysis of existing data on macroinvertebrate communities of European alpine streams supported this conclusion, and demonstrated that occurrence-based functional diversity indices are highly sensitive to the traits included in their calculation. Overall, our findings suggest that the search for quantitative trait-environment relationships using single traits or simple combinations of multiple traits is unlikely to be productive. Instead, there is a need to embrace the value of conceptual frameworks linking community responses to environmental change via traits which correspond to the axes of life-history models. Through a novel integration of tools and databases, our flexible framework can address this need.

The Impact of Metal-Rich Sediments Derived from Mining on Freshwater Stream Life.

Metal-rich sediments have the potential to impair life in freshwater streams and rivers and, thereby, to inhibit recovery of ecological conditions after any remediation of mine water discharges. Sediments remain metal-rich over long time periods and have long-term potential ecotoxicological interactions with local biota, unless the sediments themselves are physically removed or replaced by less metal-rich sediment. Laboratory-derived environmental quality standards are difficult to apply to the field situation, as many complicating factors exist in the real world. Therefore, there is a strong case to consider other, field-relevant, measures of toxic effects as alternatives to laboratory-derived standards and to seek better biological tools to detect, diagnose and ideally predict community-level ecotoxicological impairment. Hence, this review concentrated on field measures of toxic effects of metal-rich sediment in freshwater streams, with less emphasis on laboratory-based toxicity testing approaches. To this end, this review provides an overview of the impact of metal-rich sediments on freshwater stream life, focusing on biological impacts linked to metal contamination.

Histological chorioamnionitis is predicted by early infant C-reactive protein in preterm infants and correlates with neonatal outcomes.

AIM: Histological chorioamnionitis (HCA) is associated with preterm birth and adverse neonatal outcomes. We evaluated the rise in C-reactive protein (CRP) in preterm infants as a predictor of HCA severity and outcomes. METHODS: Consecutive preterm infants, born January 2009 to January 2014 in the National Maternity Hospital, Dublin, under 32 weeks' gestation or <1.5 kg birthweight, were included. Histological chorioamnionitis was staged as maternal inflammatory response, foetal inflammatory response and non-HCA. RESULTS: Preterm infants (n = 518) were included with a mean gestational age 28.5 ± 2.8 weeks, birthweight 1.1 ± 0.3 kg, and 53.5% were male. Histological chorioamnionitis was found in 25.4%. Histological chorioamnionitis was present in 93.7% when CRP > 5 mg/L, 65.2% when CRP 1-5 mg/L and in 19.4% when CRP < 1 mg/L. When both the immature to total neutrophil (IT) ratio was >0.2 and the CRP > 1 mg/L the positive predictive value and negative predictive value for HCA were 92.5% and 84.9%, respectively. Histological chorioamnionitis was associated with more resuscitation and respiratory distress syndrome (both P < .001). A CRP > 10 mg/L was associated with a foetal inflammatory response and increased early-onset sepsis. CONCLUSION: Higher early CRP was a surrogate predictor of HCA and correlated with the severity of HCA. Higher CRP and HCA were associated with adverse early outcomes.

Troponin T correlates with MRI results in neonatal encephalopathy.

AIM: Troponin is a sensitive marker of asphyxia in term infants mirroring the myocardial injury sustained in global hypoxia-ischaemia. In addition, troponin is a sensitive marker of severity of stroke in adults and neonatal encephalopathy (NE). We aimed to examine the relationship between troponin T in infants with perinatal asphyxia and brain injury on MRI and correlate with neurodevelopmental outcome. METHODS: Serum troponin was sampled in infants requiring resuscitation at birth and/or neonatal encephalopathy in a tertiary referral neonatal centre. Birth history, clinical parameters, neuroimaging and developmental outcome (Bayley Scores of Infant Development [BSID] III) were evaluated. RESULTS: Infants with perinatal asphyxia (n = 54) had serum troponin T measured and 27 required therapeutic hypothermia. Troponin T levels on days 1 and 2 were predictive of need for TH, development of seizures and grade II/III NE (AUC = 0.7; P-values < .001), troponin T levels on days 1, 2 and 3 were highly significant predictors of mortality (AUC = 0.99, P-values .005). The cut-off values of troponin T for best prediction of mortality were 0.84, 0.63 and 0.58 ng/mL on days 1, 2 and 3, respectively. Troponin T on day 3 of life was predictive of injury in the combined area of basal ganglia/watershed on MRI (AUC 0.70; P-value = .045). CONCLUSION: Infants with brain injury on neuroimaging following perinatal asphyxia had significantly elevated serum troponin, and troponin also correlated with developmental scores at 2 years. Further studies combining troponin and MRI may assist in the classification of neonatal brain injury to define aetiology, prognosis and response to treatment.

Laryngoscope burn risk in neonatal intubation.

LARYNGOSCOPE BURNS IN NEONATAL INTUBATION: Following burns during neonatal intubation, we mounted an in vitro study of laryngoscopes to determine the temperatures reached during clinical use. The temperature of 10 different bulb laryngoscopes heads and two fibre optic heads were measured with a thermocouple, once opened, and upon closing. Within 60 s, all ten laryngoscopes, with light-bulb sources, had gained significant heat to cause thermal injury to neonatal skin. Laryngoscopes with LED light source and fibre optic heads did not. CONCLUSION: We recommend that the bulb laryngoscope blade, if used, is not left open prior to intubation and that it is closed between intubation attempts. What is Known: • The preterm epidermis is particularly vulnerable to injury. What is New: • Bulb laryngoscope light bulbs consistently reach temperatures sufficient to burn neonatal skin in less than 100 s in an in vitro study. • Bulb light safety advice should be incorporated into intubation guidelines.

How Do Pain, Fatigue, Depressive, and Cognitive Symptoms Relate to Well-Being and Social and Physical Functioning in the Daily Lives of Individuals With Multiple Sclerosis?

OBJECTIVE: To examine the relative association between daily change in pain, fatigue, depressed mood, and cognitive function and 4 outcomes-positive affect and well-being, ability to participate in social roles and activities, upper extremity (UE) functioning, and lower extremity (LE) functioning. DESIGN: Data analysis, multilevel mixed modeling. SETTING: General community. PARTICIPANTS: Ambulatory adults (N=102) with multiple sclerosis. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Customized short-forms of the Quality of Life in Neurological Disorders positive affect and well-being, UE functioning, and LE functioning item banks and the Patient-Reported Outcomes Measurement Information System ability to participate in social roles and activities item bank adapted for daily use and administered as end-of-day diaries. RESULTS: Above and beyond the effects of demographic and clinical covariates, daily pain was associated with 3 of the 4 outcomes; days of higher than usual pain were related to lower same-day social participation (unstandardized ß, B=-1.00; P=.002), UE functioning (B=-1.04; P=.01), and LE functioning (B=-.71; P=.04). Daily fatigue and depressed mood were independently related to daily positive affect and well-being; days of worse fatigue (B=-.54; P=.006) and depressed mood (B=-1.17; P<.0001) were related to lower same-day well-being. CONCLUSIONS: The results indicate the role of fluctuations in symptoms in daily functioning and quality of life of individuals with multiple sclerosis. Daily increases in pain intensity are related to social and physical functioning, whereas increases in fatigue and depressed mood are related to lower daily well-being. Findings implicate a person-centered approach to monitoring and treating symptoms.

Comparative Evaluation of Disease Induced by Three Strains of Tobacco etch virus in Capsicum annuum L.

Tobacco etch virus (TEV; genus Potyvirus) strains HAT, Mex21, and N were evaluated comparatively for their pathogenicity and effects on growth of Capsicum annuum L. 'Calwonder'. Each TEV strain induced an initial systemic symptom of vein-clearing but subsequent disease symptoms ranged from mild (HAT) to moderate (Mex21) to severe (N). Effects on plant growth parameters closely reflected disease symptoms induced by each TEV strain. HAT-infected Calwonder plants did not differ from the healthy control for plant height, internode lengths, and aboveground fresh weight of shoots. Root dry weight, however, was less for HAT-infected plants than for the healthy control. Mex21 affected plants more severely, with significantly shorter plant height (at 20, 30, and 40 days postinoculation), reduced root dry weight, and shortened internodes compared with HAT and healthy control treatments. Aboveground fresh weight of Mex21-infected plants was significantly less than for the healthy control. N induced significant negative effects relative to each of the other treatments for plant height, aboveground shoot fresh weight, root dry weight, and internode lengths. The effects on Calwonder fruit production mimicked disease severity and effects on plant growth for the respective TEV strains.

Renal function and novel urinary biomarkers in infants with neonatal encephalopathy.

AIM: Perinatal asphyxia is associated with multi-organ injury including acute kidney injury (AKI). New urinary biomarkers may detect more subtle renal injury. METHODS: Urinary biomarkers (albumin, beta-2 microglobulin, cystatin-C, epidermal growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, uromodulin) were serially measured from days 1 to 7 in term infants with perinatal asphyxia and controls and compared to 'Kidney Disease Improving Global Outcome' scoring of renal injury and to encephalopathy grade. RESULTS: A total of 255 urine samples were taken from infants exposed to perinatal asphyxia (n = 82) and term controls (n = 10). Thirty-nine infants underwent therapeutic hypothermia, four died and 30 infants had acute kidney injury. Infants with acute kidney injury had significantly higher levels of urinary albumin (day 2), cystatin-C (days 1, 2, 3 and 7), neutrophil gelatinase-associated lipocalin (days 2, 3 and 7) and osteopontin (days 2, 3 and 7) and lower epidermal growth factor and uromodulin (day 1) compared to those without AKI. Day 2 cystatin-C predicted AKI with an area under receiver operating characteristic curve of 0.89, p < 0.001, cut-off 9.8 × 104  pg/mL. NE grade II/III infants had significantly elevated levels of urinary cystatin-C, neutrophil gelatinase-associated lipocalin and decreased EGF compared to grade 0/I infants. CONCLUSION: Asphyxiated infants who develop acute kidney injury have significantly altered urinary biomarkers postnatally. Validation of neonatal AKI urinary biomarkers in a large prospective study is required. Long-term follow-up of infants post-asphyxial insult for chronic renal injury is advised.

Differential disease symptoms and full-length genome sequence analysis for three strains of Tobacco etch virus.

Tobacco etch virus (TEV) strains HAT, Mex21, and N have been the focus of numerous studies to dissect a host resistance mechanism in Capsicum spp. Little is known, however, about their general pathogenicity and genomic sequence data are not available on the TEV strains Mex21 and N. Four Nicotiana spp. were evaluated after inoculation with each TEV strain. Nicotiana tabacum 'Kentucky 14' and N. clevelandii plants expressed varied systemic symptoms dependent on the TEV strain; however, disease severity increased from HAT (mild mosaic symptoms) to Mex21 (more severe mosaic symptoms with stunting) to N (severe chlorosis and stunting). Nicotiana tabacum 'Samsun' plants developed relatively milder symptoms and N. glutinosa plants remained symptomless, although they were systemically infected. The genome of each TEV strain was sequenced and shown to consist of 9,495 nucleotides and a polyprotein of 3,054 amino acids. Comparison of their nucleotide sequences relative to the original HAT sequence (GenBank Accession No. M11458) revealed 95, 92, and 92 % identity for HAT-AU (from Auburn University), Mex21, and N, respectively. HAT-AU had 91 % sequence identity with Mex21 and N, while Mex21 and N were more closely related with 98 % nucleotide sequence identity. Similarly, the amino acid sequence identities for the full-length polyprotein ranged from 95 % for HAT-AU when compared with N to a high of 98 % identity between Mex21 and N.

Disparities in cancer care in individuals with severe mental illness: A narrative review.

Individuals with severe mental illness (SMI) have higher mortality rates from cancer than individuals without SMI. The aim of this paper is to highlight these disparities in cancer care in individuals with SMI and suggest potential solutions. We conducted a narrative review of published papers, focusing on mortality, incidence, behavioral and provider risk factors, screening, diagnosis, treatment, and palliative care among individuals with SMI and cancer. The literature does not provide a clear consensus on whether a difference in cancer incidence exists among individuals with SMI compared to the general population. However, it is evident that individuals with SMI have higher mortality from cancer. Factors such as increased cancer related risk behavior, mental health stigma, and difficulty accessing cancer care contribute to this mortality difference. The literature also indicates lower screening rates, delayed and improper diagnosis and treatment, as well as inadequate clinical trial enrollment in individuals with SMI. While the literature is inconclusive regarding disparities in palliative care, we outline key concepts to provide the best possible end of life care to this population. We also summarize strategies to address disparities at the screening, diagnostic, and treatment levels and describe general strategic approaches to improve cancer care in individuals with SMI. We highlight patient-related, physician-related, and healthcare/systems-related factors leading to disparities in cancer care in individuals with SMI. Future research must examine the effectiveness of proposed solutions to guide evidence-based practices.

Vitamin D nutritional status in preterm infants and response to supplementation.

Little is known about vitamin D status in preterm infants and their response to supplementation. To investigate this, we assessed serum 25-hydroxyvitamin D (25OHD) levels using RIA in a consecutive sample of stable preterm very low birth weight (VLBW) infants (born ≤ 32 weeks gestation or birth weight ≤ 1·5 kg), and we explored associated factors. Serum 25OHD level was first assessed once infants were tolerating feeds (n 274). If this first 25OHD level was below 50 nmol/l (20 ng/ml), which is the level associated with covering requirements in terms of skeletal health in the majority, then we recommended prolonged augmented vitamin D intake ( ≥ 10 µg (400 IU) daily) from a combination of fortified feeds and vitamin supplements and follow-up re-assessment at approximately 6 weeks corrected age (n 148). The first assessment, conducted at a median for chronological age of 18 (interquartile range (IQR) 11-28) d, found that 78 % had serum 25OHD levels below 50 nmol/l. Multivariable analysis demonstrated that the determinants of serum 25OHD levels were duration of vitamin D supplementation and gestational age at birth (r 2 0·215; P< 0·001). At follow-up, after a median of 104 (IQR 78-127) d, 87 % achieved levels ≥ 50 nmol/l and 8 % had levels >125 nmol/l, a level associated with potential risk of harm. We conclude that low 25OHD levels are an issue for preterm VLBW infants, warranting early nutritional intervention. In infants with serum 25OHD levels < 50 nmol/l, a vitamin D intake of ≥ 10 µg (400 IU) daily achieves target levels in the majority; however, further work is needed to determine the exact dose to safely meet target levels without overcorrection.

Factors Associated With Developing Neurocognitive Adverse Events in Patients Receiving Lorlatinib After Progression on Other Targeted Therapies.

INTRODUCTION: The safety profile of lorlatinib includes neurocognitive adverse events (NAEs). Baseline factors associated with developing NAEs remain poorly characterized. METHODS: Records from patients who received lorlatinib through prospective studies at Massachusetts General Hospital (MGH, n = 124) or the phase 1/2 B7461001 (NCT01970865; n = 248) study were reviewed to identify potential associations between comorbidities, baseline medications, and NAEs. RESULTS: Most patients experienced a NAE (MGH: 60%, B7461001: 49%). Cognitive effects occurred in 40% and 29% of patients in the MGH and B7461001 cohorts, respectively. Brain metastases (p = 0.008), brain radiation (p = 0.033), psychiatric illness (p = 0.008), psychiatric medications (p < 0.001), antiepileptics (p < 0.001), and stimulants (p = 0.026) were associated with developing cognitive effects in B7461001. Mood effects occurred in 36% and 23% of patients in the MGH and B7461001 cohorts, respectively. In the MGH cohort, psychiatric illness (p = 0.02) and stimulants (p = 0.01) were associated with developing mood effects whereas brain surgery (p = 0.020), psychiatric medications (p < 0.001), benzodiazepines (p = 0.002), and sedatives (p = 0.034) were associated with developing mood effects in B7461001. Psychotic effects were infrequent (MGH: 3%, B7461001: 9%) and were associated with brain surgery in the MGH cohort (p = 0.001) and age in B7461001 (p = 0.014). Speech effects were observed in 23% and 11% of patients in the MGH and B7461001 cohorts, respectively. Brain radiation (p = 0.012) and antiepileptics (p < 0.001) were associated with speech effects in B7461001. Dose reductions were implemented for 52% and 18% of patients with NAEs in MGH and B7461001 cohorts, respectively, with mitigating effect. CONCLUSIONS: Neurocognitive effects from lorlatinib are common. Lorlatinib-related NAEs may be influenced by multiple factors, including brain metastases, brain radiation, psychiatric illness, and use of neurotropic medications.

What do macroinvertebrate indices measure? Stressor-specific stream macroinvertebrate indices can be confounded by other stressors.

Monitoring programmes worldwide use biota to assess the "health" of water bodies. Indices based on biota are used to describe the change in status of sites over time, to identify progress against management targets and to diagnose the causes of biological degradation. A variety of numerical stressor-specific biotic indices have been developed based on the response of biota to differences in stressors among sites. Yet, it is not clear how variation in pressures within sites, over what time period, and in what combination has the greatest impact on different biotic groups. An understanding of how temporal variation in pressures influences biological assessment indices would assist in setting achievable targets and help focus catchment-scale mitigation strategies to ensure that they deliver the desired improvements in biological condition.Hydrochemical data provided by a network of high-frequency (15 or 30 min) automated monitoring stations over 3 years were matched to replicated biological data to understand the influence of spatio-temporal variation in pollution pressures on biological indices. Hydrochemical data were summarised in various ways to reflect central tendency, peaks, troughs and variation over 1-90 days before the collection of each biological sample. An objective model selection procedure was used to determine which hydrochemical determinand, and over what time period, best explained variation in the biological indices.Stressor-specific indices derived from macroinvertebrates which purportedly assess stress from low flows, excess fine sediment, nutrient enrichment, pesticides and organic pollution were significantly inter-correlated and reflected periods of low oxygen concentration, even though only one index (ASPTWHPT, average score per taxon) was designed for this purpose. Changes in community composition resulting from one stressor frequently lead to confounding effects on stressor-specific indices.Variation in ASPTWHPT was best described by dissolved oxygen calculated as Q5 over 10 days, suggesting that low oxygen events had most influence over this period. Longer-term effects were apparent, but were masked by recovery. Macroinvertebrate abundance was best described by Q95 of stream velocity over 60 days, suggesting a slower recovery in numbers than in the community trait reflected by ASPTWHPT.Although use of ASPTWHPT was supported, we recommend that additional independent evidence should be used to corroborate any conclusions regarding the causes of degradation drawn from the other stressor-specific indices. The use of such stressor-specific indices alone risks the mistargeting of management strategies if the putative stressor-index approach is taken to be more reliable than the results herein suggest.

Long-term trends in crayfish invasions across European rivers.

Europe has experienced a substantial increase in non-indigenous crayfish species (NICS) since the mid-20th century due to their extensive use in fisheries, aquaculture and, more recently, pet trade. Despite relatively long invasion histories of some NICS and negative impacts on biodiversity and ecosystem functioning, large spatio-temporal analyses of their occurrences are lacking. Here, we used a large freshwater macroinvertebrate database to evaluate what information on NICS can be obtained from widely applied biomonitoring approaches and how usable such data is for descriptions of trends in identified NICS species. We found 160 time-series containing NICS between 1983 and 2019, to infer temporal patterns and environmental drivers of species and region-specific trends. Using a combination of meta-regression and generalized linear models, we found no significant temporal trend for the abundance of any species (Procambarus clarkii, Pacifastacus leniusculus or Faxonius limosus) at the European scale, but identified species-specific predictors of abundances. While analysis of the spatial range expansion of NICS was positive (i.e. increasing spread) in England and negative (significant retreat) in northern Spain, no trend was detected in Hungary and the Dutch-German-Luxembourg region. The average invasion velocity varied among countries, ranging from 30 km/year in England to 90 km/year in Hungary. The average invasion velocity gradually decreased over time in the long term, with declines being fastest in the Dutch-German-Luxembourg region, and much slower in England. Considering that NICS pose a substantial threat to aquatic biodiversity across Europe, our study highlights the utility and importance of collecting high resolution (i.e. annual) biomonitoring data using a sampling protocol that is able to estimate crayfish abundance, enabling a more profound understanding of NICS impacts on biodiversity.

Tobacco etch virus infectivity in Capsicum spp. is determined by a maximum of three amino acids in the viral virulence determinant VPg.

Potyvirus resistance in Capsicum spp. has been attributed to amino acid substitutions at the pvr1 locus that cause conformational shifts in eukaryotic translation initiation factor eIF4E. The viral genome-linked protein (VPg) sequence was isolated and compared from three Tobacco etch virus (TEV) strains, highly aphid-transmissible (HAT), Mex21, and N, which differentially infect Capsicum genotypes encoding Pvr1(+), pvr1, and pvr1(2). Viral chimeras were synthesized using the TEV-HAT genome, replacing HAT VPg with Mex21 or N VPg. TEV HAT did not infect pepper plants homozygous for either the pvr1 or pvr1(2) allele. However, the novel chimeric TEV strains, TEVHAT(Mex21-VPg) and TEV-HAT(N-VPg), infected pvr1 and pvr1(2) pepper plants, respectively, demonstrating that VPg is the virulence determinant in this pathosystem. Three dimensional structural models predicted interaction between VPg and the susceptible eIF4E genotype in every case, while resistant genotypes were never predicted to interact. To determine whether there is a correlation between physical interaction of VPg with eIF4E and infectivity, the effects of amino acid variation within VPg were assessed. Interaction between pvr1(2) eIF4E and N VPg was detected in planta, implying that the six amino acid differences in N VPg relative to HAT VPg are responsible for restoring the physical interaction and infectivity.

Separating natural from human enhanced methane emissions in headwater streams.

Headwater streams are natural sources of methane but are suffering severe anthropogenic disturbance, particularly land use change and climate warming. The widespread intensification of agriculture since the 1940s has increased the export of fine sediments from land to streams, but systematic assessment of their effects on stream methane is lacking. Here we show that excess fine sediment delivery is widespread in UK streams (n = 236) and, set against a pre-1940s baseline, has markedly increased streambed organic matter (23 to 100 g m-2), amplified streambed methane production and ultimately tripled methane emissions (0.2 to 0.7 mmol CH4 m-2 d-1, n = 29). While streambed methane production responds strongly to organic matter, we estimate the effect of the approximate 0.7 °C of warming since the 1940s to be comparatively modest. By separating natural from human enhanced methane emissions we highlight how catchment management targeting the delivery of excess fine sediment could mitigate stream methane emissions by some 70%.

Phase II Study of Lorlatinib in Patients With Anaplastic Lymphoma Kinase-Positive Lung Cancer and CNS-Specific Relapse.

PURPOSE: The CNS is a recurrent site of progression in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) lung cancer. Lorlatinib is a third-generation ALK inhibitor developed to penetrate the CNS and overcome ALK resistance mutations. We conducted a phase II study to evaluate the intracranial activity of lorlatinib in patients with CNS-only progression on second-generation ALK inhibitors. METHODS: Patients with ALK+ lung cancer who had intracranial progression on ≥ 1 ALK inhibitor without measurable extracranial disease received lorlatinib 100 mg once daily. The primary end point was intracranial disease control rate at 12 weeks per modified RECIST v1.1. Secondary end points included intracranial progression-free survival, intracranial objective response rate, and safety/tolerability. RESULTS: Twenty-three patients were enrolled between November 2016 and January 2019. Fifteen (65%) patients had irradiated CNS metastases, with a median of 20.2 months between radiation and lorlatinib. Control of intracranial disease was observed in 21 (95%) evaluable patients at 12 weeks. The intracranial objective response rate was 59% with six complete and seven partial responses. The median intracranial progression-free survival was 24.6 months (95% CI, 20.2 to not reached). With a median follow-up of 16.8 months, nine patients developed disease progression, including four patients with CNS progression. The most common treatment-related adverse events were hypercholesterolemia (96%), hypertriglyceridemia (87%), edema (65%), cognitive effects (52%), and mood effects (43%). Three patients discontinued treatment because of toxicity, including two patients with fatal respiratory events. CONCLUSION: Lorlatinib induced durable intracranial disease control in patients with CNS-only relapse on second-generation ALK inhibitors, suggesting that tumors with CNS-limited progression on brain-penetrant ALK tyrosine kinase inhibitors remain ALK-dependent.

Neonatal brachial plexus injury: comparison of incidence and antecedents between 2 decades.

OBJECTIVE: We sought to compare the incidence and antecedents of neonatal brachial plexus injury (BPI) in 2 different 5-year epochs a decade apart following the introduction of specific staff training in the management of shoulder dystocia. STUDY DESIGN: All infants with BPI were prospectively identified during 2004 through 2008. Injuries were correlated with maternal details and intrapartum events and compared with the earlier series. RESULTS: Of 41,828 deliveries during 2004 through 2008, 72 infants with BPI were identified (1.7/1000), compared to 54 cases (1.5/1000) from 1994 through 1998 (P = .4); 9 injuries (12.5%) were persistent from 2004 through 2008, compared with 10 (18.5%) earlier (P = .4). There were no significant differences between the 2 time periods with respect to maternal parity, obesity, or prolonged pregnancy, although the cesarean section rate had increased from 10.7 to 18.4%. CONCLUSION: Despite training in the management of shoulder dystocia and a rising institutional cesarean section rate, the incidence of BPI has remained unchanged compared with 10 years earlier.