Impact of hydrological drought occurrence, duration, and severity on Murray-Darling basin water quality.

The severity and frequency of droughts are projected to increase globally due to climate change, but the effects of this on water quality are uncertain. The Murray-Darling Basin (MDB) is the largest river system in Australia and has been impacted by droughts of varying severity within recent decades. In this study, we assessed the influence of hydrological droughts and their characteristics (severity and duration) on water quality, utilising a long-term (1980-2017) dataset from two monitoring sites. The main drought periods, and their duration and severity, were identified using the calculated Standardised Drought Index values (SDI) from averaged monthly streamflow data. While several hydrological drought periods were identified, the longest duration and greatest severity were during the Millennium Drought (1998-2010). Nutrient loads and concentrations of Total Nitrogen and Total Phosphorus of drought and post-drought periods were significantly different. The drought period showed the lowest median and interquartile range of nutrient (total nitrogen, TN; oxidised nitrogen, NOX; total phosphorus, TP; and soluble reactive phosphorus, SRP) concentrations and loads for both sites, whereas the highest nutrient loads and concentrations were reported during the post-drought period (approx. 1 × 103 to 1 × 105 kg day-1 increase in nutrient loads). Our analysis found significant relationships between nutrient loads and SDI during droughts. The load of N and P in the initial flush post-drought increased with drought at both sites. This suggests that nutrients were retained in the landscape during the drought and released in higher loads post-drought when the catchment became wetter, the hydrology was activated, and nutrients were mobilised. Hydrology is a key driver controlling the water quality within the inter-drought period and the peak nutrient loads post-drought. The duration and the severity of droughts had a significant (p = 0.01) influence on peak TN and TP monthly loads but not cumulative loads over a 12-month period. Hydrological droughts are important factors in controlling the water quality of the MDB. Therefore, management efforts should be focused on reducing the occurrence and duration of these events, along with the implementation of catchment nutrient control measures.

Synthetase and Hydrolase Specificity Collectively Excludes 2'-Deoxyguanosine from Bacterial Alarmone.

In response to starvation, virtually all bacteria pyrophosphorylate the 3'-hydroxy group of GTP or GDP to produce two messenger nucleotides collectively denoted as (p)ppGpp. Also known as alarmones, (p)ppGpp reprograms bacterial physiology to arrest growth and promote survival. Intriguingly, although cellular concentration of dGTP is two orders of magnitude lower than that of GTP, alarmone synthetases are highly selective against using 2'-deoxyguanosine (2dG) nucleotides as substrates. We thus hypothesize that production of 2dG alarmone, (p)pp(dG)pp, is highly deleterious, which drives a strong negative selection to exclude 2dG nucleotides from alarmone signaling. In this work, we show that the B. subtilis SasB synthetase prefers GDP over dGDP with 65,000-fold higher kcat/Km, a specificity stricter than RNA polymerase selecting against 2'-deoxynucleotides. Using comparative chemical proteomics, we found that although most known alarmone-binding proteins in Escherichia coli cannot distinguish ppGpp from pp(dG)pp, hydrolysis of pp(dG)pp by the essential hydrolase, SpoT, is 1,000-fold slower. This inability to degrade 2'-deoxy-3'-pyrophosphorylated substrate is a common feature of the alarmone hydrolase family. We further show that SpoT is a binuclear metallopyrophoshohydrolase and that hydrolysis of ppGpp and pp(dG)pp shares the same metal dependence. Our results support a model in which 2'-OH directly coordinates the Mn2+ at SpoT active center to stabilize the hydrolysis-productive conformation of ppGpp. Taken together, our study reveals a vital role of 2'-OH in alarmone degradation, provides new insight on the catalytic mechanism of alarmone hydrolases, and leads to the conclusion that 2dG nucleotides must be strictly excluded from alarmone synthesis because bacteria lack the key machinery to down-regulate such products.

Mechanisms and inhibition of Porcupine-mediated Wnt acylation.

Wnt signalling is essential for regulation of embryonic development and adult tissue homeostasis1-3, and aberrant Wnt signalling is frequently associated with cancers4. Wnt signalling requires palmitoleoylation on a hairpin 2 motif by the endoplasmic reticulum-resident membrane-bound O-acyltransferase Porcupine5-7 (PORCN). This modification is indispensable for Wnt binding to its receptor Frizzled, which triggers signalling8,9. Here we report four cryo-electron microscopy structures of human PORCN: the complex with the palmitoleoyl-coenzyme A (palmitoleoyl-CoA) substrate; the complex with the PORCN inhibitor LGK974, an anti-cancer drug currently in clinical trials10; the complex with LGK974 and WNT3A hairpin 2 (WNT3Ap); and the complex with a synthetic palmitoleoylated WNT3Ap analogue. The structures reveal that hairpin 2 of WNT3A, which is well conserved in all Wnt ligands, inserts into PORCN from the lumenal side, and the palmitoleoyl-CoA accesses the enzyme from the cytosolic side. The catalytic histidine triggers the transfer of the unsaturated palmitoleoyl group to the target serine on the Wnt hairpin 2, facilitated by the proximity of the two substrates. The inhibitor-bound structure shows that LGK974 occupies the palmitoleoyl-CoA binding site to prevent the reaction. Thus, this work provides a mechanism for Wnt acylation and advances the development of PORCN inhibitors for cancer treatment.

Seventy years of data from the world's longest grazed and irrigated pasture trials.

Pastures are the most widespread land use, globally. The Winchmore trials were established in 1948-1949 in Canterbury, New Zealand and examined either different rates of phosphorus (P) fertiliser on the same irrigation schedule (Fertiliser trial), or different irrigation scheduling at the same rate of P application (Irrigation trial). About 96,000 records of soil chemistry and physical data and pasture yield and botanical composition are available along with nearly 7000 soil samples. These data have been used in 475 publications that have explored topics as diverse as: improvements in sheep, dairy and deer production; the efficacy and scheduling of irrigation; improvements in pasture and crop production; agronomic and environmental soil and water research; and entomology. In addition to above topics, these data are invaluable for calibrating models to predict long-term issues like the accumulation of soil carbon or contaminants like cadmium and informing policy on climate change and agricultural practices. The data and soil samples are available for use and may yet yield discoveries, unforeseen 70 years ago.

In the face of climate change and exhaustive exercise: the physiological response of an important recreational fish species.

Cobia (Rachycentron canadum) support recreational fisheries along the US mid- and south-Atlantic states and have been recently subjected to increased fishing effort, primarily during their spawning season in coastal habitats where increasing temperatures and expanding hypoxic zones are occurring due to climate change. We therefore undertook a study to quantify the physiological abilities of cobia to withstand increases in temperature and hypoxia, including their ability to recover from exhaustive exercise. Respirometry was conducted on cobia from Chesapeake Bay to determine aerobic scope, critical oxygen saturation, ventilation volume and the time to recover from exhaustive exercise under temperature and oxygen conditions projected to be more common in inshore areas by the middle and end of this century. Cobia physiologically tolerated predicted mid- and end-of-century temperatures (28-32°C) and oxygen concentrations as low as 1.7-2.4 mg l-1. Our results indicated cobia can withstand environmental fluctuations that occur in coastal habitats and the broad environmental conditions their prey items can tolerate. However, at these high temperatures, some cobia did suffer post-exercise mortality. It appears cobia will be able to withstand near-future climate impacts in coastal habitats like Chesapeake Bay, but as conditions worsen, catch-and-release fishing may result in higher mortality than under present conditions.

The impacts of warming and hypoxia on the performance of an obligate ram ventilator.

Climate change is causing the warming and deoxygenation of coastal habitats like Chesapeake Bay that serve as important nursery habitats for many marine fish species. As conditions continue to change, it is important to understand how these changes impact individual species' behavioral and metabolic performance. The sandbar shark (Carcharhinus plumbeus) is an obligate ram-ventilating apex predator whose juveniles use Chesapeake Bay as a nursery ground up to 10 years of age. The objective of this study was to measure juvenile sandbar shark metabolic and behavioral performance as a proxy for overall performance (i.e. fitness or success) when exposed to warm and hypoxic water. Juvenile sandbar sharks (79.5-113.5 cm total length) were collected from an estuary along the eastern shore of Virginia and returned to lab where they were fitted with an accelerometer, placed in a respirometer and exposed to varying temperatures and oxygen levels. Juvenile sandbar shark overall performance declined substantially at 32°C or when dissolved oxygen concentration was reduced below 3.5 mg l-1 (51% oxygen saturation between 24-32°C). As the extent of warm hypoxic water increases in Chesapeake Bay, we expect that the available sandbar shark nursery habitat will be reduced, which may negatively impact the population of sandbar sharks in the western Atlantic as well as the overall health of the ecosystem within Chesapeake Bay.

Spontaneous Otogenic Pneumocephalus: Case Series and Update on Management.

Objectives This study is aimed to report the largest independent case series of spontaneous otogenic pneumocephalus (SOP) and review its pathophysiology, clinical presentation, and treatment. Design Four patients underwent a middle cranial fossa approach for repair of the tegmen tympani and tegmen mastoideum. A comprehensive review of the literature regarding this disease entity was performed. Setting U.S. tertiary academic medical center. Participants: Patients presenting to the lead author's clinic or to the emergency department with radiographic evidence of SOP. Symptoms included headache, otalgia, and neurologic deficits. Main Outcome Measures Patients were assessed for length of stay, postoperative length of stay, and neurologic outcome. Three of four patients returned to their neurologic baseline following repair. Results Four patients were successfully managed via a middle cranial fossa approach to repairing the tegmen mastoideum. Conclusion The middle cranial fossa approach is an effective strategy to repair defects of the tegmen mastoideum. SOP remains a clinically rare disease, with little published information on its diagnosis and treatment.

Rhodolith primary and carbonate production in a changing ocean: The interplay of warming and nutrients.

Rhodolith beds, like many other marine ecosystems, are affected by climate change that is causing an increase in the magnitude and frequency of extreme high temperature events (heat waves). Unfortunately, this does not represent the sole peril for these communities, as coastal urbanization in conjunction with altered precipitation patterns can increase terrestrial-derived nutrient input. In Brazil, rhodolith beds are among the most extensive coastal benthic ecosystems, but despite their vast distribution and great ecological and economic importance, studies on the productivity of these communities and the impact of changing environmental conditions are almost non-existent. This study addressed the individual and combined effects of increases in temperature and nutrient concentration on the physiological performance of two widely distributed rhodolith species, Lithothamnion crispatum and Melyvonnea erubescens. The results showed species-specific responses in net photosynthetic performance, with no response in L. crispatum, while M. erubescens responded negatively to both increase in temperature and nutrients. In contrast, calcification in both species showed a significant decline at high temperature. No interactive effects were found between temperature and nutrients, yet their combined negative effects were additive, resulting in negative daily-integrated net productivity and a large decline in daily carbonate production in both species. This has strong implications for rhodolith bed primary productivity and carbonate production, as heat waves may potentially cause a strong decline in carbonate production (ca. 50% loss), accompanied by a severe drop in primary productivity that will be even more pronounced under high-nutrient conditions. Also, the species-specific responses to changes in temperature and nutrient concentration suggest that the magnitude of impact of these factors on rhodolith bed productivity will depend on the species dominating the community and may finally result in changes in rhodolith community composition.

Repair of Temporal Bone Defects via the Middle Cranial Fossa Approach: Treatment of 2 Pathologies With 1 Operation.

BACKGROUND: Temporal bone dehiscence (TBD) often results in leakage of cerebrospinal fluid (CSF) and/or encephalocele. TBD can also occur over the superior semicircular canal, causing debilitating vertigo. Both can be repaired surgically, but traditional treatment is focused only on one pathology, not both. OBJECTIVE: To report our experience in the treatment of TBD via the middle cranial fossa (MCF) approach. METHODS: A retrospective review was conducted for all patients who underwent MCF approach for surgical repair of any temporal fossa dehiscence. RESULTS: A total of 34 patients underwent a total of 37 surgeries. Obesity was prevalent; 21 patients (61.8%) were obese (BMI [body mass index] > 30 kg/m2), and 7 (20.6%) were overweight (BMI 25-30 kg/m2). The most common presenting symptom was hearing disturbance (70.3%), followed by otorrhea (51.4%). Empty sella was noted on computed tomography or magnetic resonance imaging in 15 patients (45.5%). Eight of the 34 patients (23.5%) were found to have superior semicircular canal dehiscence (SCD). Hearing improved with surgical intervention in 25 of 26 patients with hearing loss as a presenting symptom (96%). CSF resolved in 18 of 19 cases (95%). Seventy-three percent of patients reported at least minimal improvement in vertigo. CONCLUSION: TBD may present with symptoms of CSF leak/encephalocele, but may also present with superior SCD. We recommend consistent review of the temporal bone imaging to check for superior SCD, and repair of the SCD first to prevent complications involving the labyrinth and cochlea. MCF approach using a multilayer repair without a lumbar drain is highly effective with minimal risk of complications.

Early prediction of a significant patent ductus arteriosus in infants <32 weeks gestational age.

BACKGROUND: The optimal thresholds for identification of preterm infants at greatest risk for adverse sequelae related to patent ductus arteriosus have not been well delineated. Our aim was to determine hemodynamic parameters in the first 24 hours using continuous non-invasive vital and structural measurements to predict which infants required PDA treatment in our institution. METHODS: Retrospective secondary analysis of data from infants born 23 to 32 weeks gestational age with cardiac output and stroke volume via electrical cardiometry, cerebral tissue oximetry measurements, mean arterial blood pressure (BP), heart rate, and oxygen saturation and functional echocardiography results at 12 hours of life were recorded when available (93 percent of subjects). RESULTS: A total of 292 infants, of which 55 (26±2 weeks, 862±268 grams) were treated for PDA. Treated infants demonstrated increased left ventricular output (p < 0.001) and lower mean BP (p = 0.010). The optimal area under the receiver operating characteristic curve (AUC) for predicting PDA treatment in our all gestations cohort is a mean BP at 15 hours of life of <33 mm Hg (AUC = 0.854, p < 0.001, 95% CI 0.792, 0.916). For infants <28 weeks a mean BP at 13 hours of life of <33 mm Hg (AUC = 0.741, p < 0.050, 95% CI 0.642, 0.839). CONCLUSIONS: In our cohort increased left ventricular output and lower mean BP predicted a clinically significant PDA requiring treatment.

Investigation into the Microstructure, Texture and Rheological Properties of Chocolate Ganache.

Ganache is a mixture of chocolate and dairy. Although a popular confection, little is known about how it functions as a system. Objectives were to (1) determine if dairy fats and cocoa butter mix in ganache, (2) characterize ganache microstructure, and how structure affects texture and rheology, and (3) identify how changes in chocolate composition alter ganache. Textural analysis, differential scanning calorimetry, stress sweep tests, and microscopy were used to examine ganache formulations that varied in dairy source (cream or butter) or in solid fat content (SFC), composition or type of chocolate. Melting temperatures for all ganache formulations were lower than for chocolate, indicating that cream milk fat globules rupture during processing, and mix with cocoa butter. Altering the SFC of chocolate affected ganache hardness, spreadability, melting enthalpy, and resistance to deformation. Chocolate systems made with constant fat content and greater amounts of defatted cocoa powder relative to sugar or nonfat milk powder yielded ganache that was harder, less spreadable, and more resistant to deformation. Ganache made with commercially produced dark, milk, and white chocolates behaved similarly to model chocolate systems. Ganache attributes are affected by chocolate crystalline fat content in addition to particle phase volume-greater levels of cocoa powder, which is mostly insoluble, strengthens ganache structure, producing a firmer product, whereas greater levels of milk powder and sugar, which dissolve in the aqueous cream component, produce a softer ganache. PRACTICAL APPLICATION: Understanding how ganache functions as a system and how differences in chocolate composition affect its textural and rheological properties may allow for greater control over the desired characteristics of the final product. For example, this research shows how changing cocoa content of the chocolate affects ganache, which is useful when developing formulations involving chocolates with different cocoa percentages. There may also be cost saving implications; for example, using a chocolate with a harder cocoa butter may allow less total chocolate to be used in a formulation, while still achieving an appropriate texture.

A review of international clinical practice guidelines for the use of oxygen in the delivery room resuscitation of preterm infants.

AIM: To collate and assess international clinical practice guidelines (CPG) to determine current recommendations guiding oxygen management for respiratory stabilisation of preterm infants at delivery. METHODS: A search of public databases using the terms 'clinical practice guidelines', 'preterm', 'oxygen' and 'resuscitation' was made and complemented by direct query to consensus groups, resuscitation expert committees and clinicians. Data were extracted to include the three criteria for assessment: country of origin, gestation and initial FiO2 and target SpO2 for the first 10 minutes of life. RESULTS: A total of 45 CPGs were identified: 36 provided gestation specific recommendations (<28 to <37 weeks) while eight distinguished only between 'preterm' and 'term'. The most frequently recommended initial FiO2 were between 0.21 and 0.3 (n = 17). Most countries suggested altering FiO2 to meet SpO2 targets recommended by expert committees, However, specific five-minute SpO2 targets differed by up to 20% (70-90%) between guidelines. Five countries did not specify SpO2 targets. CONCLUSION: CPG recommendations for delivery room oxygen management of preterm infants vary greatly, particularly in regard to gestational ages, initial FiO2 and SpO2 targets and most acknowledge the lack of evidence behind these recommendations. Sufficiently large and well-designed randomised studies are needed to inform on this important practice.

Factors Related to Injury Prevention Programming by Missouri School Nurses.

Schools often offer injury prevention (IP) programs, but little is known about the types of programs provided or how school nurses decide which to choose. Nurses in the Missouri School Health Services Staffing Survey Database were sent a survey in spring, 2011, to describe school-based IP efforts being offered. A multivariate linear regression was conducted to delineate factors associated with offering IP programs. In total, 522 school nurses participated (33% response rate). The highest priority for selecting an IP program was perceived program effectiveness (92.3% agreement, n = 482). Determinants of offering IP programs included being asked to identify a speaker, being a high school, receiving funding in the last year, prioritizing evidence-based programs, perceiving that administrators support professional development, and knowing how to address patterns of injuries. School nurses should be competent in planning, implementing, and evaluating IP programs, and additional training may be required to accomplish this.

The IRIS® Registry : Purpose and perspectives.

The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) launched about 2 years ago and has already become the largest national clinical specialty data registry with nearly 50 million patient visits and over 14 million unique patients. The purpose of the registry is to support and promote continued improvement in the delivery of eye care. The perspectives that "big data" encompass are the key issues facing ophthalmology and eye care, including public health and public policy concerning disease incidence and prevalence, utilization of eye care services, natural history of disease, disease surveillance, comparative effectiveness, safety and adverse event monitoring, compliance with "best practices" and clinical guidelines, etc. The valuable real-world and current-day insights provided by the IRIS Registry and other registries like it will accelerate scientific learning and improvements in care delivery, particularly in a cost-constrained environment.

[The IRIS® Registry : Purpose and perspectives. German Version]. / Das IRIS®-Register : Ziele und Perspektiven.

The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) launched about 2 years ago and has already become the largest national clinical specialty data registry with nearly 50 million patient visits and over 14 million unique patients. The purpose of the registry is to support and promote continued improvement in the delivery of eye care. The perspectives that "big data" encompass are the key issues facing ophthalmology and eye care, including public health and public policy concerning disease incidence and prevalence, utilization of eye care services, natural history of disease, disease surveillance, comparative effectiveness, safety and adverse event monitoring, compliance with "best practices" and clinical guidelines, etc. The valuable real-world and current-day insights provided by the IRIS Registry and other registries like it will accelerate scientific learning and improvements in care delivery, particularly in a cost-constrained environment.

The use of electrical cardiometry for continuous cardiac output monitoring in preterm neonates: a validation study.

BACKGROUND: Electrical cardiometry (EC) is a continuous noninvasive method for measuring cardiac output (CO), but there are limited data on premature infants. We evaluated the utility of EC monitoring by comparing the results obtained using EC to measurements of CO and systemic blood flow using echocardiography (ECHO). METHODS: In this prospective observational study, 40 preterm neonates underwent 108-paired EC and ECHO measurements. RESULTS: There were correlations between EC-CO and left ventricular output (LVO, p < 0.005) and right ventricular output (RVO, p < 0.005) but not with superior vena cava (r = 0.093, p = 0.177). Both RVO and LVO correlated with EC with and without a hemodynamically significant ductus arteriosus (p = 0.001 and 0.008, respectively). The level of agreement was decreased in infants ventilated by high-frequency oscillation ventilators (HFOV). The bias in HFOV was also positive compared with the negative biases found in other modes of ventilation. CONCLUSION: Given the correlation of EC with LVO, RVO, and lack of confounding effects of the ductus, our results suggest that EC has promise for trending CO in the preterm infant. However, given the limitations with mode of ventilation and the lack of correlation at low LVO values, further study is needed before this technology can be for routine use.

Impact of premedication on neonatal intubations by pediatric and neonatal trainees.

OBJECTIVE: To determine if premedication and training level affect the success rates of neonatal intubations. STUDY DESIGN: We retrospectively reviewed a hospital-approved neonatal intubation database from 2003 to 2010. Intubation success rate was defined as the number of successful intubations divided by the total number of attempts, and then compared by trainee's experience level and the use of premedication. Premedication regimen included anticholinergic, analgesic and muscle relaxant agents. RESULT: There were 169 trainees who completed 1071 successful intubations with 2694 attempts. The median success rate was 36% by all trainees, and improved with training level from 29% for pediatric trainees to 50% for neonatal trainees (P<0.001). Premedication was used in 58% of intubation attempts. The median success rate was double with premedication (43% versus 22%, P<0.001). CONCLUSION: Neonatal endotracheal intubation is a challenge for trainees. Intubation success rates progressively improve with experience. Premedication is associated with improved success rates for all training levels.

Neonatal resuscitation for the preterm infant: evidence versus practice.

In an effort to determine the actual conduct of neonatal resuscitation and the errors that may be occurring during this process, we developed a method of video recording neonatal resuscitations as an ongoing quality assurance project. We initiated video recordings of resuscitations using simple video recorders attached to an overhead warmer and reviewed the resultant tapes during biweekly quality improvement meetings. We also added the continuous recording of analog information such as heart rate, oximeter values, fraction of inspired oxygen and airway pressure. We subsequently developed a checklist that includes a preresuscitation briefing and a postresuscitation debriefing, all of which are reviewed at the same time as the video recording. We have examined the use of oxygen in the very preterm infant, the effectiveness of bag and mask ventilation, including the detection of airway obstruction during such ventilation, intubation in the delivery area and environment. In addition, we have trained our teams and leaders using Crew Resource Management and focused on improved communication. The availability of a dedicated room for resuscitation allows an increased ambient environment and the ability to provide a user-friendly setting similar to the neonatal intensive care unit to optimize performance. There are numerous opportunities for improving team and leader performance and outcomes following neonatal resuscitation. Further prospective studies are required to evaluate specific interventions.

Z-Bisdehydrodoisynolic acid (Z-BDDA): an estrogenic seco-steroid that enhances behavioral recovery following moderate fluid percussion brain injury in male rats.

Several lines of research suggest that estrogens (and estrogenic compounds) are neuroprotective following experimental traumatic brain injury. However, therapeutic use of estrogens in this and other regards remains controversial. Therefore, analysis of estrogen-like compounds without potential problems similar to estrogens seems warranted. (±) Z-Bisdehydrodoisynolic acid (Z-BDDA) is a seco-steroid that has potent estrogenic as well as antioxidant activities in vitro and in vivo. We evaluated the therapeutic potential of Z-BDDA (300µg/0.1cc/100g body weight, sc) to promote the recovery of behavioral function following lateral fluid percussion injury (FPI) to the brain in male rats. Two hours subsequent to FPI, treatment with Z-BDDA began with a bolus subcutaneous (sc) injection followed by booster treatments given 24 and 48h later. Behavioral testing was initiated on the second day after FPI and results of Z-BDDA treatments were compared to treatment with vehicle only and to sham FPI surgery. Z-BDDA effectively enhanced recovery of coordinated limb movement assessed by locomotor placing performance across the duration of the study. Z-BDDA treated animals also performed better on a spatial memory task in the Morris water maze, showing improved learning curves across days of testing. Vestibulomotor function, measured by beam walk performance, appeared to improve in Z-BDDA treated animals, however these results did not reach statistical significance (p>0.05). Following cessation of the behavioral testing, all animals underwent assessments of gross neuroanatomical pathology. Cortical lesion size and cell death analysis with Fluoro-jade B failed to reveal Z-BDDA enhanced neuroprotection. These findings support our hypothesis that Z-BDDA can facilitate behavioral recovery following FPI in adult male rats although the mechanism(s) of these effects remain to be determined.