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Lipid-protein interactions play a multitude of essential roles in membrane homeostasis. Mitochondrial membranes have a unique lipid-protein environment that ensures bioenergetic efficiency. Cardiolipin (CL), the signature mitochondrial lipid, plays multiple roles in promoting oxidative phosphorylation (OXPHOS). In the inner mitochondrial membrane, the ADP/ATP carrier (AAC in yeast; adenine nucleotide translocator, ANT in mammals) exchanges ADP and ATP, enabling OXPHOS. AAC/ANT contains three tightly bound CLs, and these interactions are evolutionarily conserved. Here, we investigated the role of these buried CLs in AAC/ANT using a combination of biochemical approaches, native mass spectrometry, and molecular dynamics simulations. We introduced negatively charged mutations into each CL-binding site of yeast Aac2 and established experimentally that the mutations disrupted the CL interactions. While all mutations destabilized Aac2 tertiary structure, transport activity was impaired in a binding site-specific manner. Additionally, we determined that a disease-associated missense mutation in one CL-binding site in human ANT1 compromised its structure and transport activity, resulting in OXPHOS defects. Our findings highlight the conserved significance of CL in AAC/ANT structure and function, directly tied to specific lipid-protein interactions. Synopsis: Three molecules of cardiolipin, the signature mitochondrial phospholipid, tightly interact with the ADP/ATP carrier (AAC/ANT). This study demonstrates that each cardiolipin-AAC/ANT interaction is structurally and functionally important. Negatively charged mutations into the cardiolipin binding sites of yeast Aac2 disrupted cardiolipin-Aac2 interaction. Aac2 tertiary structure was destabilized in the mutants with disrupted cardiolipin binding. Disruption of cardiolipin binding impaired Aac2 transport activity in a site-specific manner. A disease-associated mutation in human ANT1 compromises ANT1 structure and transport activity due to a disturbed cardiolipin-ANT1 interaction. The binding of three cardiolipin molecules to the mitochondrial ADP/ATP carrier supports the protein's tertiary structure and transport activity. [ABSTRACT FROM AUTHOR]

Using High‐Throughput Experimentation (HTE), a visible light‐mediated etherification method was developed, employing the organic photocatalyst thioxanthen‐9‐one (TXO) and a commercially available, air‐stable nickel source. Design of Experiments (DoE) techniques were utilized in conjunction with HTE to identify optimal reaction conditions which are mild, cost‐effective, robust and therefore suitable for use in an industrial setting. A diverse substrate scope was prepared via parallel synthesis and selected examples were demonstrated on a 4.2 mmol scale in batch. Furthermore, the reaction was successfully performed on an 83 mmol scale, utilizing a standard jacketed reactor and Kessil PR160 L lamps. [ABSTRACT FROM AUTHOR]

Parasitism is nearly ubiquitous in animals and is frequently associated with fitness costs in host organisms, including reduced growth, foraging, and reproduction. In many species, males tend to be more heavily parasitized than females and thus may bear greater costs of parasitism. Sceloporus undulatus is a female‐larger, sexually size dimorphic lizard species that is heavily parasitized by chigger mites (Eutrombicula alfreddugesi). In particular, the intensity of mite parasitism is higher in male than in female juveniles during the period of time when sex differences in growth rate lead to the development of sexual size dimorphism (SSD). Sex‐biased differences in fitness costs of parasitism have been documented in other species. We investigated whether there are growth costs of mite ectoparasitism, at a time coinciding with sex differences in growth rate and the onset of SSD. If there are sex‐biased growth costs of parasitism, then this could suggest a contribution to the development of SSD in S. undulatus. We measured growth and mite loads in two cohorts of unmanipulated, field‐active yearlings by conducting descriptive mark‐recapture studies during the activity seasons of 2016 and 2019. Yearling males had consistently higher mid‐summer mite loads and consistently lower growth rates than females. However, we found that growth rate and body condition were independent of mite load in both sexes. Furthermore, growth rates and mite loads were higher in 2019 than in 2016. Our findings suggest that juveniles of S. undulatus are highly tolerant of chigger mites and that any costs imposed by mites may be at the expense of functions other than growth. We conclude that sex‐biased mite ectoparasitism does not contribute to sex differences in growth rate and, therefore, does not contribute to the development of SSD. [ABSTRACT FROM AUTHOR]

Mitochondria play essential roles in metabolic support and signaling within all cells. Congenital and acquired defects in mitochondria are responsible for several pathologies, including premature entrance to cellar senescence. Conversely, we examined the consequences of dysfunctional telomere‐driven cellular senescence on mitochondrial biogenesis and function. We drove senescence in vitro and in vivo by deleting the telomere‐binding protein TRF2 in fibroblasts and hepatocytes, respectively. Deletion of TRF2 led to a robust DNA damage response, global changes in transcription, and induction of cellular senescence. In vitro, senescent cells had significant increases in mitochondrial respiratory capacity driven by increased cellular and mitochondrial volume. Hepatocytes with dysfunctional telomeres maintained their mitochondrial respiratory capacity in vivo, whether measured in intact cells or purified mitochondria. Induction of senescence led to the upregulation of overlapping and distinct genes in fibroblasts and hepatocytes, but transcripts related to mitochondria were preserved. Our results support that mitochondrial function and activity are preserved in telomere dysfunction‐induced senescence, which may facilitate continued cellular functions. [ABSTRACT FROM AUTHOR]

But let's return to Civitarese and Bion. The I second hypothesis of i Civitarese connects to a new theme: The analytic couple forms the basic assumptions in groups as described by Bion. The encounter of two people in "O", or the incomprehensible (ineffable), the "divine", the "maternal", as developed by Bion, is to be distinguished from the three basic assumptions in groups (Bion, [4], p. 147). DOI: https://doi.org/10.1080/00207578.2021.1927045 The title "Experiences in Groups as a Key to "Late" Bion" announces the news that has been discussed for some time from different psycho-dynamic points of view. [Extracted from the article]

Background: Newborn screening (NBS) has largely eliminated the physical and neurodevelopmental effects of untreated congenital hypothyroidism (CH). Many countries, including Australia, have progressively lowered NBS bloodspot thyroid‐stimulating hormone (b‐TSH) thresholds. The impact of these changes is still unclear. Objectives: To evaluate the performance of CH NBS following the reduction of b‐TSH thresholds in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia, from 15 to 8 mIU/L, and to determine the clinical outcomes of cases detected by these thresholds. Methods: NBS data of 346 849 infants born in NSW/ACT, Australia from 1 November, 2016–1 March, 2020 inclusive were analysed. A clinical audit was conducted on infants with a preliminary diagnosis of CH born between 1 January, 2016–1 December, 2020 inclusive. Results: The lowered b‐TSH threshold (≥8 mIU/L, ~99.5th centile) detected 1668 infants (0.48%), representing an eight‐fold increase in recall rate, of whom 212 of 1668 (12.7%) commenced thyroxine treatment. Of these 212 infants, 62 (29.2%) (including eight cases with a preliminary diagnosis of thyroid dysgenesis) had an initial b‐TSH 8–14.9 mIU/L. The positive predictive value for a preliminary diagnosis of CH decreased from 74.3% to 12.8% with the lowered threshold. Proportionally, more pre‐term infants received a preliminary CH diagnosis on screening with the lower threshold (16.1% of 62) than with the higher threshold (8.0% of 150). Conclusion: Clinically relevant CH was detected using the lowered threshold, albeit at the cost of an eight‐fold increase in recall rate. Further clinical and economic studies are required to determine whether benefits of lowered screening thresholds outweigh potential harms from false‐positive results on infants, their families and NBS programs. [ABSTRACT FROM AUTHOR]

We investigated if diarrhoea‐causing bacteria, including Yersinia species, could mimic the symptoms of appendicitis and lead to surgery. This prospective observational cohort study (NCT03349814) included adult patients undergoing surgery for suspected appendicitis. Rectal swabs were analysed with polymerase chain reaction (PCR) for Yersinia, Campylobacter, Salmonella, Shigella and Aeromonas spp. Blood samples were analysed routinely and with an in‐house ELISA serological test for Yersinia enterocolitica antibodies. We compared patients without appendicitis and patients with appendicitis confirmed by histopathology. The outcomes included PCR‐confirmed infection with Yersinia spp., serologic‐confirmed infection with Y. enterocolitica, PCR‐confirmed infection with other diarrhoea‐causing bacteria and Enterobius vermicularis confirmed by histopathology. A total of 224 patients were included, 51 without and 173 with appendicitis, and followed for 10 days. PCR‐confirmed infection with Yersinia spp. was found in one patient (2%) without appendicitis and no patients (0%) with appendicitis (p = 0.23). Serology was positive for Y. enterocolitica for the same patient without appendicitis and two patients with appendicitis (p = 0.54). Campylobacter spp. were detected in 4% vs 1% (p = 0.13) of patients without and with appendicitis, respectively. Infection with Yersinia spp. and other diarrhoea‐causing microorganisms in adult patients undergoing surgery for suspected appendicitis was rare. [ABSTRACT FROM AUTHOR]

Alterations of fibroblast growth factor receptors (FGFRs) are common in bladder and other cancers and result in disrupted signalling via several pathways. Therapeutics that target FGFRs have now entered the clinic, but, in common with many cancer therapies, resistance develops in most cases. To model this, we derived resistant sublines of two FGFR‐driven bladder cancer cell lines by long‐term culture with the FGFR inhibitor PD173074 and explored mechanisms using expression profiling and whole‐exome sequencing. We identified several resistance‐associated molecular profiles. These included HRAS mutation in one case and reversible mechanisms resembling a drug‐tolerant persister phenotype in others. Upregulated IGF1R expression in one resistant derivative was associated with sensitivity to linsitinib and a profile with upregulation of a YAP/TAZ signature to sensitivity to the YAP inhibitor CA3 in another. However, upregulation of other potential therapeutic targets was not indicative of sensitivity. Overall, the heterogeneity in resistance mechanisms and commonality of the persister state present a considerable challenge for personalised therapy. Nevertheless, the reversibility of resistance may indicate a benefit from treatment interruptions or retreatment following disease relapse in some patients. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Intracellular infiltration of bacteria into host cells complicates medical and surgical treatment of bacterial joint infections. Unlike soft tissue infections, septic arthritis and infection‐associated inflammation destroy cartilage that does not regenerate once damaged. Herein, we show that glycolytic pathways are shared by methicillin‐resistant Staphylococcus aureus (MRSA) proliferation and host inflammatory machinery in septic arthritis. MRSA readily penetrates host cells and induces proinflammatory cascades that persist after conventional antibiotic treatment. The glycolysis‐targeting drug dimethyl fumarate (DMF) showed both bacteriostatic and anti‐inflammatory effects by hindering the proliferation of intracellular MRSA and dampening excessive intraarticular inflammation. Combinatorial treatment with DMF and vancomycin further reduced the proliferation and re‐emergence of intracellular MRSA. Combinatorial adjuvant administration of DMF with antibiotics alleviated clinical symptoms of septic arthritis by suppressing bacterial burden and curbing inflammation to protect cartilage and bone. Our results provide mechanistic insight into the regulation of glycolysis in the context of infection and host inflammation toward development of a novel therapeutic paradigm to ameliorate joint bioburden and destruction in septic arthritis. Synopsis: Septic arthritis has limitations such as intracellular bacteria and inflammatory tissue disruption even after conventional treatment. This study shows evidence of the potential of repurposing of glycolysis targeting DMF in conjunction with a conventional antibiotic to ameliorate septic arthritis. Intraarticular inflammation and glycolysis are induced in the setting of MRSA septic arthritis.Inhibition of glycolysis with DMF normalizes the production of proinflammatory markers within the joint space.DMF inhibits bacterial replication, intracellular bioburden, and biofilm formation via bacteriostatic effects.Administration of DMF adjuvant to systemic antibiotics alleviates the clinical symptoms and pathologic signs of septic arthritis. [ABSTRACT FROM AUTHOR]

The analysis of drug material in the field is an important function of law enforcement agencies, forensic drug laboratories, and drug checking services. Portable testing techniques employed by these different groups range from inexpensive screening tools with low discriminating power, such as presumptive chemical color tests, to more sophisticated portable analytical techniques that behave as miniaturized versions of their laboratory counterparts, such as gas chromatography–mass spectrometry (GC–MS). Rapid non‐destructive analysis in the field and non‐laboratory environments is afforded by portable and handheld Fourier transform infrared (FTIR) spectrometers with little to no sample preparation, while handheld Raman analyzers have the added potential for drug material identification through sealed packaging using spatially offset Raman spectroscopy (SORS). Utilization of the most suitable testing technique for the given environment is demonstrated at international borders and airports wherein ion mobility spectroscopy (IMS) is frequently employed for the detection of drug (and explosive) residues owing to its ease of operation and rapid analysis. Advances in technology and materials have provided analysts with new portable testing techniques, including paper spray ionization–MS (PSI‐MS), an ambient MS technique that provides sensitive, rapid, and reliable analysis without the need for sample preparation steps. A growing area of research and interest in the development of sensitive and selective optical and electrochemical portable (bio)sensors for in‐field analysis of drug material indicates that new commercial sensors for drug detection will be available in the foreseeable future. This article is categorized under:Forensic Chemistry and Trace Evidence > Controlled and Emerging Drug CompoundsForensic Chemistry and Trace Evidence > Emerging Technologies and MethodsToxicology > Drug Analysis [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is associated with morbidity and mortality. Urinary biomarkers may disentangle its clinical heterogeneity. Olfactomedin 4 (OLFM4) is a secreted glycoprotein expressed in stressed neutrophils and epithelial cells. In septic mice, OLFM4 expression localized to the kidney's loop of Henle (LOH) and was detectable in the urine. We hypothesized that urine OLFM4 (uOLFM4) will be increased in patients with AKI and sepsis. Urine from critically ill pediatric patients was obtained from a prospective study based on AKI and sepsis status. uOLFM4 was quantified with a Luminex immunoassay. AKI was defined by KDIGO severe criteria. Sepsis status was extracted from the medical record based on admission diagnosis. Immunofluorescence on pediatric kidney biopsies was performed with NKCC2, uromodulin and OLFM4 specific antibodies. Eight patients had no sepsis, no AKI; 7 had no sepsis but did have AKI; 10 had sepsis, no AKI; 11 had sepsis and AKI. Patients with AKI had increased uOLFM4 compared to no/stage 1 AKI (p = 0.044). Those with sepsis had increased uOLFM4 compared to no sepsis (p = 0.026). uOLFM4 and NGAL were correlated (r2 0.59, 95% CI 0.304–0.773, p = 0.002), but some patients had high uOLFM4 and low NGAL, and vice versa. Immunofluorescence on kidney biopsies demonstrated OLFM4 colocalization with NKCC2 and uromodulin, suggesting expression in the thick ascending LOH (TALH). We conclude that AKI and sepsis are associated with increased uOLFM4. uOLFM4 and NGAL correlated in many patients, but was poor in others, suggesting these markers may differentiate AKI subgroups. Given OLFM4 colocalization to human TALH, we propose OLFM4 may be a LOH‐specific AKI biomarker. [ABSTRACT FROM AUTHOR]

Background: Supracondylar fractures are the most common elbow fracture. There have been no studies published analysing flexion‐type fractures in the Australian paediatric population. This paper aims to investigate flexion‐type supracondylar fractures in an Australian paediatric population. Eight hundred and three paediatric supracondylar elbow fractures were retrospectively reviewed at one hospital over a 5 year time period. The focus was on flexion‐type fractures. Methods: Supracondylar fractures that presented to the Women's and Children's Hospital Emergency Department between 2015 and 2020 were retrospectively reviewed. Fractures were classified on plain radiographs according to the Modified Gartland Classification System. Injury and treatment data were collected for flexion‐type fractures. Results: Twenty‐one (2.6%) of fractures were flexion‐type. The average age of injury was 6.8 years old. Flexion‐type fractures were more common in females (62%) and with high energy mechanisms (81%). Ulnar nerve palsies occurred in five cases (24%). Two ulna nerve palsies did completely resolve at 3 months follow up. One open fracture occurred. No vascular injuries occurred. Ten of the 21 flexion‐type fractures (48%) were treated surgically. Conclusions: The authors conclude that: flexion fractures are uncommon, they occur more often after high energy mechanisms such as falls from monkey bars, swings, or trampolines. Flexion‐type fractures occur more often in slightly older females. The ulnar nerve is most frequently injured and in the current study—exclusively injured. At 3 month follow up, spontaneous nerve recovery had occurred in three of the five cases (60%). [ABSTRACT FROM AUTHOR]

The restoration of shellfish reefs to soft‐sediment environments often relies on the translocation of donor stock, typically from aquaculture, to the seafloor. In New Zealand, subadult green‐lipped mussels (Perna canaliculus) grown on subtidal aquaculture long‐lines are being considered over adult conspecifics to increase restoration efficiency but are currently limited by predation and hydrodynamic dislodgment following transfer to the seabed. In this study, the survival of subadult mussels from five different sources representing a range of growth conditions (i.e. subtidal aquaculture long‐lines 1 and 2, subtidal shellfish aquaculture baskets 1, wild intertidal reefs 1 and 2) were compared across separate translocations (1 and 2) to see if careful consideration of stock source could improve subadult mussel survival following transfer to the seafloor. Mussel morphology (shell strength, attachment thread structure) and clumping behavior (perimeter:area ratios, clump densities, clump complexity) were compared among populations to explain relationships among prior stock growth conditions, mussel size, and survival. Following experimental translocations, high survival (>90%) was closely related to decreases in perimeter:area ratios of mussel clumps and increases in clump complexity. High survival groups of mussels were selected from stock with high shell compression strength (subtidal aquaculture long‐line 2, 95.5% survival), greater attachment thread number and thickness (aquaculture basket 1, 92.3% survival), or some combination of the two (wild intertidal reef 2, 99.3% survival). This study supports further consideration for incorporating subadult mussels into restoration provided they are selected from sources that produce individuals with the resistant characteristics outlined in this study. [ABSTRACT FROM AUTHOR]

Objective: We propose a novel cue‐based asynchronous brain–computer interface(BCI) for neuromodulation via the pairing of endogenous motor cortical activity with the activation of somatosensory pathways. Methods: The proposed BCI detects the intention to move from single‐trial EEG signals in real time, but, contrary to classic asynchronous‐BCI systems, the detection occurs only during time intervals when the patient is cued to move. This cue‐based asynchronous‐BCI was compared with two traditional BCI modes (asynchronous‐BCI and offline synchronous‐BCI) and a control intervention in chronic stroke patients. The patients performed ankle dorsiflexion movements of the paretic limb in each intervention while their brain signals were recorded. BCI interventions decoded the movement attempt and activated afferent pathways via electrical stimulation. Corticomotor excitability was assessed using motor‐evoked potentials in the tibialis‐anterior muscle induced by transcranial magnetic stimulation before, immediately after, and 30 min after the intervention. Results: The proposed cue‐based asynchronous‐BCI had significantly fewer false positives/min and false positives/true positives (%) as compared to the previously developed asynchronous‐BCI. Linear‐mixed‐models showed that motor‐evoked potential amplitudes increased following all BCI modes immediately after the intervention compared to the control condition (p <0.05). The proposed cue‐based asynchronous‐BCI resulted in the largest relative increase in peak‐to‐peak motor‐evoked potential amplitudes(141% ± 33%) among all interventions and sustained it for 30 min(111% ± 33%). Interpretation: These findings prove the high performance of a newly proposed cue‐based asynchronous‐BCI intervention. In this paradigm, individuals receive precise instructions (cue) to promote engagement, while the timing of brain activity is accurately detected to establish a precise association with the delivery of sensory input for plasticity induction. [ABSTRACT FROM AUTHOR]

Pure squamous cell carcinoma (SCC) is the most common pure variant form of bladder cancer, found in 2–5% of cases. It often presents late and is unresponsive to cisplatin‐based chemotherapy. The molecular features of these tumours have not been elucidated in detail. We carried out whole‐exome sequencing (WES), copy number, and transcriptome analysis of bladder SCC. Muscle‐invasive bladder cancer (MIBC) samples with no evidence of squamous differentiation (non‐SD) were used for comparison. To assess commonality of features with urothelial carcinoma with SD, we examined data from SD samples in The Cancer Genome Atlas (TCGA) study of MIBC. TP53 was the most commonly mutated gene in SCC (64%) followed by FAT1 (45%). Copy number analysis revealed complex changes in SCC, many differing from those in samples with SD. Gain of 5p and 7p was the most common feature, and focal regions on 5p included OSMR and RICTOR. In addition to 9p deletions, we found some samples with focal gain of 9p24 containing CD274 (PD‐L1). Loss of 4q35 containing FAT1 was found in many samples such that all but one sample analysed by WES had FAT1 mutation or deletion. Expression features included upregulation of oncostatin M receptor (OSMR), metalloproteinases, metallothioneins, keratinisation genes, extracellular matrix components, inflammatory response genes, stem cell markers, and immune response modulators. Exploration of differentially expressed transcription factors identified BNC1 and TFAP2A, a gene repressed by PPARG, as the most upregulated factors. Known urothelial differentiation factors were downregulated along with 72 Kruppel‐associated (KRAB) domain‐containing zinc finger family protein (KZFP) genes. Novel therapies are urgently needed for these tumours. In addition to upregulated expression of EGFR, which has been suggested as a therapeutic target in basal/squamous bladder cancer, we identified expression signatures that indicate upregulated OSMR and YAP/TAZ signalling. Preclinical evaluation of the effects of inhibition of these pathways alone or in combination is merited. [ABSTRACT FROM AUTHOR]

Background: The AABB‐ISCT Joint Working Group Stability Project Team (SPT) was assigned to roadmap a path toward standardization of cryopreserved hematopoietic stem/progenitor cell (HSPC) stability programs. HSPC stability encompasses a broad scope of conditions including non‐frozen ("fresh") and cryopreserved cell products, and varying methods for storage, thaw, and administration. This report assessed current practices and focused solely on cryopreserved HSPC cell therapy products to establish preliminary recommendations for a stability program roadmap. Methods: A survey was prepared by the SPT and distributed to ISCT and AABB members. Survey results were summarized and recommendations were outlined based on the responses from the survey. This report highlights current practices for cryopreserved HSPC stability programs, including additional considerations and recommendations. Results and Discussion: Eighty‐two (82) centers worldwide participated in the survey. Survey results indicate variability across programs. HSPC stability depends on multiple factors within the processing facility (e.g., cryopreservation techniques, reagents used, and storage temperature) and independent variables (e.g., donor‐related factors and starting material variability). While retention of hematopoietic engraftment potential is the primary goal for cryopreserved HSPC stability, engraftment results should not be used as the sole metric for stability programs. Based on the survey results, the SPT provides recommendations for consideration. Conclusions: The SPT recommendations for best practices are not intended to replace existing standards. The survey results emphasize the need for the community to optimize best practices and consider initiating collaborative projects to improve the standardization of cryopreserved HSPC stability programs for cell therapy products. [ABSTRACT FROM AUTHOR]

Baseflow is critical to sustaining streamflow in the Upper Colorado River Basin. Therefore, effective water resources management requires estimates of baseflow response to climatic changes. This study provides the first estimates of projected baseflow changes from historical (1984–2012) to thirty‐year periods centered around 2030, 2050, and 2080 under warm/wet, median, and hot/dry climatic conditions using a hybrid statistical‐deterministic baseflow model. Total baseflow supplied to the Lower Colorado River Basin may decline by up to 33%, although this value may increase in the near future by 6% under warm/wet conditions. The percentage of baseflow lost during in‐stream transport is projected to increase by 1%–5% relative to historical conditions. Results highlight that climate‐driven changes in high‐elevation hydrology have impacts on basinwide water availability. Study results have implications for human and ecological water availability in one of the most heavily managed watersheds in the world. Plain Language Summary: Baseflow (groundwater flowing to streams) is estimated to contribute over 50% of the total streamflow in the Upper Colorado River Basin and is thus crucial for sustaining ecological and human water needs in this highly managed area. Baseflow may be sensitive to changing climate, but the sensitivity is not well constrained. To estimate baseflow response to climate change, we tested how warm/wet, median, and hot/dry future climate scenarios affect baseflow in the basin using a hydrologic model. Results show that the largest declines in baseflow may occur in the headwater streams, and the total baseflow delivered to the Lower Colorado River Basin may decline by up to 33%, although delivery may increase in the near future by 6% under a warm/wet climate. We hypothesize that basinwide baseflow declines because of greater increases in evapotranspiration relative to precipitation in the future. Baseflow loss during in‐stream transport is projected to increase by 1%–5%. The changes in baseflow may affect both human and ecological water users in an area where water supply does not always meet demand. Key Points: Upper Colorado River Basin deliveries to the Lower Colorado River Basin are projected to decline by the end of the 21st century despite potential increases in precipitation and baseflow in some areasThe largest baseflow changes are projected to occur in higher elevation headwater catchments and have substantial basinwide effectsBaseflow loss during in‐stream transport is projected to increase relative to historical conditions [ABSTRACT FROM AUTHOR]

Climate warming in high‐latitude regions is thawing carbon‐rich permafrost soils, which can release carbon to the atmosphere and enhance climate warming. Using a coupled model of long‐term peatland dynamics (Holocene Peat Model, HPM‐Arctic), we quantify the potential loss of carbon with future climate warming for six sites with differing climates and permafrost histories in Northwestern Canada. We compared the net carbon balance at 2100 CE resulting from new productivity and the decomposition of active layer and newly thawed permafrost peats under RCP8.5 as a high‐end constraint. Modeled net carbon losses ranged from −3.0 kg C m−2 (net loss) to +0.1 kg C m−2 (net gain) between 2015 and 2100. Losses of newly thawed permafrost peat comprised 0.2%–25% (median: 1.6%) of "old" C loss, which were related to the residence time of peat in the active layer before being incorporated into the permafrost, peat temperature, and presence of permafrost. The largest C loss was from the permafrost‐free site, not from permafrost sites. C losses were greatest from depths of 0.2–1.0 m. New C added to the profile through net primary productivity between 2015 and 2100 offset ∼40% to >100% of old C losses across the sites. Differences between modeled active layer deepening and flooding following permafrost thaw resulted in very small differences in net C loss by 2100, illustrating the important role of present‐day conditions and permafrost aggradation history in controlling net C loss. Plain Language Summary: The thawing of permafrost in tundra, fen, bog, and other peatland wetlands can enhance climate change through releasing carbon from the soil. Using a model for six sites in western Canada, we estimate how much carbon will be lost by 2100 under a high‐end emissions scenario. While these peatlands continue to accumulate carbon in the surface soil layers through enhanced vegetation growth, more carbon is lost from slightly deeper in the soil profile. As a result, most sites were projected to lose relatively small amounts of carbon compared to how much they contain (<5%). Little of the carbon lost was from newly thawed permafrost, while the largest carbon losses were from the permafrost‐free site. In sites where permafrost thawed, the carbon losses were related to peatland and permafrost history. Key Points: Simulated carbon balance in peatlands with and without permafrost using process‐based model from 8000 BP to 2100 CEModeled decomposition losses from active layer peat (0.2–1.0 m) were the predominant carbon source, not deeper peat or newly thawed permafrostModeled new peat accumulation offset a large fraction of C losses but future changes in vegetation productivity are poorly understood [ABSTRACT FROM AUTHOR]

The use of illicit drugs across the world causes issues for users, healthcare workers and the public. Therefore, rapid and reliable onsite testing methods to detect these drugs are required. In this study, seven commercial surface‐enhanced Raman spectroscopy (SERS) substrates A–G were compared for the analysis of cocaine. These substrates were compared using scanning electron microscopy to study the surface structure and Raman spectroscopy and to determine if there was any enhancement of the cocaine bands. Substrate B provided the best enhancement of known cocaine vibrational bands, allowing the detection down to concentrations of 1 ng/mL in standards and 10 ng/mL extracted from the oral fluid. The results showed that SERS is an ideal method for future rapid onsite analysis of illicit drugs in oral fluid. Commercial SERS substrates were compared for the analysis of cocaine. Substrate B provided the best result and was further tested with lower concentrations and extracts from the oral fluid. The application to oral fluid testing could prove useful for future onsite analysis. [ABSTRACT FROM AUTHOR]

Widespread resource extraction and habitat degradation have severely reduced functionally important subtidal mussel reefs globally. While methods for restoring oyster reefs are becoming increasingly well‐established, the development of techniques for the effective restoration of mussel reefs remain in their infancy and face biological and logistical challenges. This study investigated the potential use of subadult and juvenile green‐lipped mussels (Perna canaliculus) for mussel reef restoration with the aim of understanding factors related to subadult and juvenile mussel survival after transfer to the seafloor. Small‐scale (m2) field experiments were conducted subtidally in a New Zealand harbor to assess subadult and juvenile mussel survival after translocation to soft‐sediment seafloor, the efficacy of biodegradable substrate to support reef development, and whether juvenile mussel survival was related to changes in seeding density. Results demonstrated survival of cultured subadult and juvenile mussels after transfer to soft‐sediment seafloor only when completely protected from mobile predators. Attachment to biodegradable substrate alone was insufficient to prevent the loss of cultured juvenile mussels, while ~80% of wild subadult mussels survived translocation to the seafloor without predator protection—indicating a certain level of resilience. Changes in seeding density failed to prevent loss of cultured juvenile mussels. This study supports further consideration for incorporating cultured subadult and juvenile mussels into restoration, provided subadult and juvenile mussels can be protected until they become established as adults. [ABSTRACT FROM AUTHOR]

Infection is a devastating complication following an open fracture. We investigated whether local rifampin‐loaded hydrogel can combat infection and improve healing in a murine model of methicillin‐resistant Staphylococcus aureus (MRSA) osteomyelitis. A transverse fracture was made at the tibia midshaft of C57BL/6J mice aged 10–12 weeks and stabilized with an intramedullary pin. A total of 1 × 106 colony‐forming units (CFU) of MRSA was inoculated. A collagen‐based hydrogel containing low‐dose (60 μg) and high‐dose (300 μg) rifampin was applied before closure. Postoperative treatment response was assessed through bacterial CFU counts from tissue and hardware, tibial radiographs and microcomputed tomography (μCT), immunohistochemistry, and histological analyses. All untreated MRSA‐infected fractures progressed to nonunion by 28 days with profuse MRSA colonization. Infected fractures demonstrated decreased soft callus formation on safranin O stain compared to controls. Areas of dense interleukin‐1β stain were associated with poor callus formation. High‐dose rifampin hydrogels reduced the average MRSA load in tissue (p < 0.0001) and implants (p = 0.041). Low‐dose rifampin hydrogels reduced tissue bacterial load by 50% (p = 0.021). Among sterile models, 88% achieved union compared to 0% of those infected. Mean radiographic union scale in tibia scores improved from 6 to 8.7 with high‐dose rifampin hydrogel (p = 0.024) and to 10 with combination local/systemic rifampin therapy (p < 0.0001). μCT demonstrated reactive bone formation in MRSA infection. Histology demonstrated restored fracture healing with bacterial elimination. Rifampin‐loaded hydrogels suppressed osteomyelitis, prevented implant colonization, and improved healing. Systemic rifampin was more effective at eliminating infection and improving fracture healing. Further investigation into rifampin‐loaded hydrogels is required to correlate these findings with clinical efficacy. [ABSTRACT FROM AUTHOR]

Researchers have pointed out a wide variety of organizational effects attributable to workplace romances, concluding that the impact of such romances on the workgroup can range from positive to negative. To date, however, little research has attempted to pinpoint the elements leading to this divergence. We suggest that coworker evaluation of a romance or anticipatory injustice may play a key role in influencing the positive or negative impact of the relationship on the workgroup at large. Our model proposes that three separate mechanisms (procedural fairness, intragroup cognitive dissonance, and normative adjustment), each corresponding to a different domain of evaluation, may mediate the apparent relationship between coworker evaluation of a romance and various aspects of group performance. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The synthetically versatile pinacol boronic ester group (Bpin) is generally thought of as a bulky moiety because of the two adjacent quaternary sp3‐hydribized carbon atoms in its diol backbone. However, recent diastereoselective reactions reported in the literature have cast doubt on this perception. Reported herein is a detailed experimental and computational analysis of Bpin and structurally related boronic esters which allows determination of three different steric parameters for the Bpin group: the A‐value, ligand cone angle, and percent buried volume. All three parameters suggest that the Bpin moiety is remarkably small, with the planarity of the oxygen‐boron‐oxygen motif playing an important role in minimising steric interactions. Of the three steric parameters, percent buried volume provides the best correlation between steric size and diastereoselectivity in a Diels–Alder reaction. [ABSTRACT FROM AUTHOR]

A practical, catalytic entry to α,α,α‐trisubstituted (α‐tertiary) primary amines by C−H functionalisation has long been recognised as a critical gap in the synthetic toolbox. We report a simple and scalable solution to this problem that does not require any in situ protection of the amino group and proceeds with 100 % atom‐economy. Our strategy, which uses an organic photocatalyst in combination with azide ion as a hydrogen atom transfer (HAT) catalyst, provides a direct synthesis of α‐tertiary amines, or their corresponding γ‐lactams. We anticipate that this methodology will inspire new retrosynthetic disconnections for substituted amine derivatives in organic synthesis, and particularly for challenging α‐tertiary primary amines. [ABSTRACT FROM AUTHOR]

The National Institute on Aging IMbedded Pragmatic Alzheimer's Disease and Alzheimer's Disease–Related Dementias Clinical Trials (IMPACT) Collaboratory serves as a national resource for the conduct of embedded pragmatic clinical trials to improve the care of people living with dementia (PLWD) in partnership with the healthcare systems that serve them. Inherent in this objective is the need to train and support a cadre of investigators prepared to conduct this work now and in the future. The Training Core of the IMPACT Collaboratory supports the training of investigators to become experts in this field through three objectives: (1) curricula development and dissemination; (2) network generation and navigation; and (3) a career development award program. The innovative approach of the Training Core will require developing content and providing training experiences that recognize the unique challenges of research at the intersection of health systems, pragmatic trials, and PLWD and their caregivers. Ultimately, we seek to build the nation's capacity to conduct research that bridges the gaps between efficacy studies to effectiveness research to implementation science. Although foundational resources in the methods of each of these areas are already available, few actually focus on pragmatic trials embedded within healthcare systems that focus on PLWD. To bring new interventions for PLWD from efficacy to widespread implementation, researchers must build diffusability, adaptability, heterogeneity, and scalability into the design of the intervention. In achieving these objectives, the Training Core will utilize the network of investigators, institutions, and stakeholders represented in the IMPACT Collaboratory. J Am Geriatr Soc 68:S21–S27, 2020. [ABSTRACT FROM AUTHOR]

A mechanistic study on use of alternating potential (i. e. electrode polarity switching) in synthetic organic electrochemical method development using the IKA ElectraSyn 2.0 is described. Unexpected product selectivity challenges revealed that alternating potential facilitated direct, rather than mediated, electrochemical benzylic C−H oxidation of toluene derivatives. Whilst constant potential irrespective of the direction of electrode polarity was expected, our in‐depth analysis revealed changes in the magnitude of applied potential with periodic switching of electrode polarity. These findings highlight an equipment engineering concern that is likely to influence and inform optimization strategies for a wide range of synthetic organic electrochemical methods under development. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether blondes have more fun, as proposed by Sir Roderick David Stewart in 1978.Design: Prospective, non-randomised crossover field study, 1-2 June 2018.Setting: Single centre medical writing course, during a break in the course program.Participants: Convenience sample of 21 healthy Danish researchers: ten blondes, nine non-blondes, and two with missing data (bald).Intervention: Participants completed a visual analogue scale (VAS) for fun and Profile of Mood States - Adolescents (POMS-A) questionnaires before and after two rides each on a waterslide (once sitting upright, once lying down). There was a wash-out between rides.Main Outcome Measures: Fun, as assessed by VAS completed moments after completing each waterslide ride.Results: Blondes did not have more fun than non-blondes, neither while sitting upright (median VAS, 60 [IQR, 23-66] v 25 [IQR, 4.5-57]; P = 0.39) nor lying down (median VAS, 70 [IQR, 60-85] v 66 [IQR, 35-80]; P = 0.62). Riding the waterslide lying down was significantly faster (median duration, 9 s; range, 8-13 s) than sitting upright (median duration, 13.6 s; range, 8-37 s; P < 0.001), and also more fun (median VAS, 72 [IQR, 59-85] v 41 [IQR, 14-66]; P = 0.002).Conclusions: Our findings are not consistent with the statement by Sir Roderick David Stewart that "blondes have more fun"; we found no evidence that blondes experience more fun or are more susceptible to mood changes than non-blondes. [ABSTRACT FROM AUTHOR]

We examine the annual, seasonal, monthly, and diurnal climate responses to the land use change (LUC) in eastern United States and Cuba during four epochs (1650, 1850, 1920, and 1992) with ensemble simulations conducted with the RegCM4 regional climate model that includes the Biosphere Atmosphere Transfer Scheme (BATS1e) surface physics package (Dickinson et al., 1993). We derived the land use (LU) data sets by harmonizing a previous reconstruction (Steyaert & Knox, 2008) with updated observations and modeled potential vegetation. The eight‐member ensembles for each epoch were driven with randomly perturbed 1990–2002 atmospheric boundary conditions derived from the National Center for Environmental Prediction global reanalysis. LUC induces statistically significant climate responses across all epochs; the largest changes occur between 1850 and 1920 with the widespread conversion of forests in the United States and forests, grassland, and woody wetlands in Cuba to agriculture. The atmospheric feedback from the aggregated grid‐cell responses attributed to physical and biophysical parameters in BATS1e alters the circulation in the lower atmosphere, thereby propagating the LUC regionally. Depending on the season and location, the altered circulation reinforces, attenuates, or has little effect on surface responses. Relative to pre‐settlement (1650), the 1992 LU produces colder mean annual air temperature (−0.09 ± 0.16 °C) and increased precipitation (0.08 ± 0.09 mm day−1) over the United States, warmer (0.08 °C) and wetter (0.03 mm day−1) conditions over Florida, and warming (0.32 °C) and drying (−0.03 mm day−1) over Cuba, indicating that LUC has played a varying role in climate change over the region. Plain Language Summary: We apply a regional climate model to evaluate the climate responses to land use (LU) and land use change (LUC) in the eastern United States and Cuba over four epochs 1650, 1850, 1920, and 1992. We used multiple simulations to create ensembles to isolate the climate responses from intrinsic variability in the model. We find that LUC alters regional circulation and leads to varying changes in temperature, precipitation, and the surface energy and water balances. From 1650 to 1992, LUC primarily associated with agriculture induced cooler temperatures and greater precipitation over the eastern United States, warmer and wetter conditions over Florida, and warmer and drier conditions over Cuba. Key Points: Ensemble perturbation simulations with RegCM4 show that land use change has contributed to the climate of the eastern United States and CubaFeedbacks from grid‐cell changes in land use alter low‐level regional circulation, which feeds back to the surface climateFrom 1650 to 1992, land use change in RegCM4 produced cooler and wetter conditions over the eastern United States, warmer and wetter conditions over Florida, and warmer and drier conditions over Cuba [ABSTRACT FROM AUTHOR]

A 4‐day‐old, 3.3 kg infant presented with suspected intestinal malrotation, necessitating emergent diagnostic laparoscopy. Intra‐operatively, the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) came back positive. This is the first case report of emergency surgery and anesthesia in a positive SARS‐CoV‐2 newborn. This report highlights a neonate with an incidental positive SARS‐CoV‐2 test, no known exposure history, negative polymerase chain reaction maternal testing, and absence of respiratory symptoms who required modified pressure control ventilation settings to adequately ventilate with the high‐efficiency particulate air filter in situ. [ABSTRACT FROM AUTHOR]

We assess monthly temperature and precipitation data derived by six statistically downscaled data sets for 14 general circulation models (GCMs) from the Climate Model Intercomparison Program Phase 5. We use a simple monthly water balance model to quantify and decompose uncertainties associated with the GCMs and statistical techniques in projections for four snow‐dominated regions in the western United States. The end‐of‐century projections from GCMs exhibit substantial variation in change over the regions (temperature range of 2.8–8.0 °C and precipitation range of −22–31%). The six downscaled data sets exhibit disparate high‐resolution representations of the magnitude and spatial patterns of future temperature (up to 2.2 °C) and precipitation (up to 30%) for a common GCM. Two data sets derived by the same downscaling method (Multivariate Adaptive Constructed Analogs) produce median losses of snow water equivalent over the Upper Colorado of 51% and 81%. The principal causes of the differences among the downscaled projections are related to the gridded observations used to bias correct the historical GCM output. Specifically, (1) whether a fixed atmospheric lapse rate (−6.5 °C/km) or a spatially and temporally varying lapse rate is used to extrapolate lower elevation observations to high‐elevations and (2) whether high‐elevation station data (e.g., SNOTEL) are included in the observations. The GCM projections are the largest source of uncertainty in the monthly water balance model simulations; however, the differences among seasonal projections produced by downscaled data sets in some regions highlight the need for careful evaluation of the statistically downscaled data in climate impact studies. Plain Language Summary: Climate change information simulated by global climate models is downscaled using statistical methods to translate spatially coarse regional projections to finer resolutions that are desirable to researchers and managers to assess local climate impacts. Several statistical downscaling methods have been developed over the past 15 years, resulting in multiple data sets derived by different methods. We apply a simple hydrology model to demonstrate how the differences among these data sets result in disparate projections of snow loss and future changes in runoff in the western United States and provide guidance to users on how to select and evaluate the appropriate data set for their needs. Key Points: Application of a water balance model reveals differences among statistically downscaled data sets result in varying future projectionsThe choice of bias correction data set is a major factor in the simulation of high‐elevation snow and the amount of snow loss in the futureThe spread among GCMs is the largest source of uncertainty in projections, but differences attributed to downscaled data can be substantial [ABSTRACT FROM AUTHOR]

Objectives: To assess the efficacy and safety of combination therapy with clomiphene citrate (CC) and anastrozole (AZ) for male hypoandrogenism. Patients and Methods: We identified patients treated with a combination of CC + AZ in the period 2014 to 2017. Data were gathered on patient characteristics and laboratory values at baseline. Total testosterone, bioavailable testosterone, oestradiol and testosterone:oestradiol ratio were measured before combination therapy (treatment with CC only) and at CC + AZ combination therapy follow‐ups. Treatment side effects were recorded; prostatic‐specific antigen and haematocrit levels were measured to assess safety after 6 months. As a secondary outcome, semen characteristics were compared at baseline and after at least 3 months of combination therapy when these data were available. Data were analysed using a paired t‐test and Wilcoxon's signed‐rank test. Results: A total of 51 men were included, with a mean age of 35.4 ± 7.4 years and a mean body mass index of 35.0 ± 8.0 kg/m2. After CC treatment, total testosterone, bioavailable testosterone, and oestradiol levels all significantly increased. AZ was added in all patients with hyperoestrogenaemia (oestradiol >50 pg/mL) or a testosterone:oestradiol ratio <10. CC + AZ therapy maintained therapeutic total testosterone and bioavailable testosterone levels while also normalizing oestradiol levels and testosterone:oestradiol ratio. Eleven patients experienced side effects: anxiety/irritability, n = 5; decreased libido, n = 4; elevated (>54%) haematocrit, n = 2. Conclusion: Combination therapy with CC + AZ is an effective and safe alternative for patients with elevated oestradiol level or low testosterone:oestradiol ratio. [ABSTRACT FROM AUTHOR]

Objectives: To describe the essential components of an Agile Implementation (AI) process, which rapidly and effectively implements evidence‐based healthcare solutions, and present a case study demonstrating its utility. Design: Case demonstration study. Setting: Integrated, safety net healthcare delivery system in Indianapolis. Participants: Interdisciplinary team of clinicians and administrators. Measurements: Reduction in dementia symptoms and caregiver burden; inpatient and outpatient care expenditures. Results: Implementation scientists were able to implement a collaborative care model for dementia care and sustain it for more than 9 years. The model was implemented and sustained by using the elements of the AI process: proactive surveillance and confirmation of clinical opportunities, selection of the right evidence‐based healthcare solution, localization (i.e., tailoring to the local environment) of the selected solution, development of an evaluation plan and performance feedback loop, development of a minimally standardized operation manual, and updating such manual annually. Conclusion: The AI process provides an effective model to implement and sustain evidence‐based healthcare solutions. [ABSTRACT FROM AUTHOR]

Abstract: CRISPR‐Cas technology has revolutionized genome engineering. While Cas9 was not the first programmable endonuclease identified, its simplicity of use has driven widespread adoption in a short period of time. While CRISPR‐Cas genome editing holds enormous potential for clinical applications, its use in laboratory settings for genotype‐phenotype studies and genome‐wide screens has led to breakthroughs in the understanding of many molecular pathways. Numerous protocols have been described for introducing CRISPR‐Cas components into cells, and here we sought to simplify and optimize a protocol for genome editing using readily available and inexpensive tools. We compared plasmid, ribonucleoprotein (RNP), and RNA transfection to determine which was method was most optimal for editing cells in a laboratory setting. We limited our comparison to lipofection‐mediated introduction because the reagents are widely available. To facilitate optimization, we developed a novel reporter assay to measure gene disruption and the introduction of a variety of exogenous DNA tags. Each method efficiently disrupted endogenous genes and was able to stimulate the introduction of foreign DNA at specific sites, albeit to varying efficiencies. RNP transfection produced the highest level of gene disruption and was the most rapid and efficient method overall. Finally, we show that very short homology arms of 30 base pairs can mediate site‐specific editing. The methods described here should broaden the accessibility of RNP‐mediated lipofection for laboratory genome‐editing experiments. [ABSTRACT FROM AUTHOR]

Abstract: We analyze climate simulations conducted with the RegCM3 regional climate model on 50‐ and 15‐km model grids to diagnose the dependence of wildfire incidence and area burned variations on monthly climate long‐term means and anomalies over North America for the period 1986–2013. We created a new wildfire database by merging the Fire Program Analysis Fire‐Occurrence Database, the National Interagency Fire Center Fire History Data, and the Canadian National Fire Database. The database includes 2,083,865 daily fire starts that burned a total of 1.25 × 108 ha in North America. We derive long‐term climatologies, standardized gamma indices, and composite climate anomalies of atmospheric circulation (500‐hPa height and wind) and various surface fields (e.g., solar radiation, soil moisture, vapor pressure deficit, and latent and sensible heat fluxes) to illustrate the climatology of burned area. The immediate and lagged monthly atmospheric circulation and surface climate anomalies differentiate high‐ and low‐fire years and the role of El Niño–Southern Oscillation in wildfire occurrence. Our approach demonstrates the association of the seasonal cycles of wildfire and climate and the strong role of climatic variability in modulating the seasonal cycle as a control of wildfire on monthly time scales. [ABSTRACT FROM AUTHOR]

Abstract: Cocaine trafficking in the form of textile impregnation is routinely encountered as a concealment method. Raman spectroscopy has been a popular and successful testing method used for in situ screening of cocaine in textiles and other matrices. Quantitative analysis of cocaine in these matrices using Raman spectroscopy has not been reported to date. This study aimed to develop a simple Raman method for quantifying cocaine using atropine as the model analogue in various types of textiles. Textiles were impregnated with solutions of atropine in methanol. The impregnated atropine was extracted using less hazardous acidified water with the addition of potassium thiocyanate (KSCN) as an internal standard for Raman analysis. Despite the presence of background matrix signals arising from the textiles, the cocaine analogue could easily be identified by its characteristic Raman bands. The successful use of KSCN normalised the analyte signal response due to different textile matrix background interferences and thus removed the need for a matrix‐matched calibration. The method was linear over a concentration range of 6.25–37.5 mg/cm2 with a coefficient of determination (R2) at 0.975 and acceptable precision and accuracy. A simple and accurate Raman spectroscopy method for the analysis and quantification of a cocaine analogue impregnated in textiles has been developed and validated for the first time. This proof‐of‐concept study has demonstrated that atropine can act as an ideal model compound to study the problem of cocaine impregnation in textile. The method has the potential to be further developed and implemented in real world forensic cases. [ABSTRACT FROM AUTHOR]

Introduction: Infertility treatments such as in vitro fertilization (IVF) impose substantial distress. However, the specific role of individual contributory factors remains unclear. We therefore compared treatment-related psychological stress in IVF treatments with (cIVF) and without (NC-IVF) gonadotropin stimulation, as cIVF includes potentially stressful factors such as ovarian stimulation, anesthesia, embryo selection and cryopreservation, whereas NC-IVF does not.Material and Methods: Women were offered to have cIVF or NC-IVF. Validated psychological questionnaires filled in online before, during and after completed treatment cycle(s) at home were used to analyze psychological distress and treatment-related satisfaction and quality of life. To avoid different pregnancy rates in the two treatment groups, one cIVF was compared with three NC-IVF therapies, resulting in the same cumulative pregnancy rate.Results: Data from 57 NC-IVF and 62 cIVF patients were evaluated. NC-IVF resulted in a similar overall clinical pregnancy rate than one cIVF. NC-IVF patients had a significantly lower level of depression (CES-D, 13.4 vs. 15.7, p < 0.05) and a higher satisfaction with the treatment (Treatment FertiQoL, 67.9 vs. 62.9, p < 0.05) compared with cIVF patients. The level of psychological distress increased during c-IVF treatment and decreased during NC-IVF treatment. In contrast, during NC-IVF treatment there was a significant increase in satisfaction with the treatment, whereas satisfaction with treatment in the cIVF patients decreased.Conclusions: Factors other than just pregnancy rate seem to have an impact on psychological stress in IVF treatment. Due to reduced psychological stress in NC-IVF, this treatment could be especially considered in psychologically stressed women. [ABSTRACT FROM AUTHOR]

In seed plants, strigolactones ( SLs) regulate architecture and induce mycorrhizal symbiosis in response to environmental cues. SLs are formed by combined activity of the carotenoid cleavage dioxygenases ( CCDs) 7 and 8 from 9- cis-β-carotene, leading to carlactone that is converted by cytochromes P450 (clade 711; MAX1 in Arabidopsis) into various SLs. As Physcomitrella patens possesses CCD7 and CCD8 homologs but lacks MAX1, we investigated if Pp CCD7 together with Pp CCD8 form carlactone and how deletion of these enzymes influences growth and interactions with the environment., We investigated the enzymatic activity of Pp CCD7 and Pp CCD8 in vitro, identified the formed products by high performance liquid chromatography ( HPLC) and LC- MS, and generated and analysed Δ CCD7 and Δ CCD8 mutants., We defined enzymatic activity of Pp CCD7 as a stereospecific 9- cis- CCD and Pp CCD8 as a carlactone synthase. Δ CCD7 and Δ CCD8 lines showed enhanced caulonema growth, which was revertible by adding the SL analogue GR24 or carlactone. Wild-type ( WT) exudates induced seed germination in Orobanche ramosa. This activity was increased upon phosphate starvation and abolished in exudates of both mutants. Furthermore, both mutants showed increased susceptibility to phytopathogenic fungi., Our study reveals the deep evolutionary conservation of SL biosynthesis, SL function, and its regulation by biotic and abiotic cues. [ABSTRACT FROM AUTHOR]

Accessible Summary We wanted to find out what people with learning disabilities think about watching television., Some people find it difficult to say what they are thinking., We worked with ten adults with learning disabilities who helped us find the right words, questions and pictures to use in our Talking Mats® about watching television., We tried out the questions on five people to see if our Talking Mats® helped them to say what they thought about television. We made some changes so that the Talking Mats® were ready to use with lots of people., Summary Background: Capturing the views of people with learning disabilities is not straightforward. Talking Mats® has been used successfully to solicit the views of such individuals. The aim was to co-produce an interview schedule using Talking Mats® on the subject of television-viewing habits and preferences of adults and young people with learning disabilities. A secondary aim was to assess the feasibility of the tool prior to a larger scale survey. Materials and Methods: A co-production process was adopted for the development of the Talking Mats ® interview. Ten adults with learning disabilities were recruited as collaborators. Six people participated in an advisory group that met on six occasions. Four supplementary members reviewed the group's work separately. The collaborators generated vocabulary for the tool, selected the most meaningful graphic symbols and reviewed the categories of television programmes. A script to accompany the Talking Mats® procedure was developed and checked for linguistic complexity. The resulting tool was piloted with five participants. The procedure was video recorded and evaluated for procedural effectiveness. Findings: Review of the video recordings from the pilot study revealed that no participant scored below the minimum effectiveness rating of 12. Areas of difficulty that were noted included: time duration of interview, tangibility of symbols and currency of vocabulary. These triggered a number of recommendations for address in the larger scale survey. Conclusions: Working with people with learning disabilities as collaborators helped to develop a tool fit for purpose. [ABSTRACT FROM AUTHOR]

Strigolactones are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, a cis-configured β-carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 ( CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product. In this study, we used 13C and 18O-labeling to shed light on the reactions catalyzed by CCD8. The characterization of the resulting carlactone by LC- MS and NMR, and the identification of the assumed, less accessible second product allowed us to formulate a minimal reaction mechanism for carlactone generation. [ABSTRACT FROM AUTHOR]

We simulate the 1950-2010 water balance for the conterminous U.S. (CONUS) with a monthly water balance model (MWBM) using the 800 m Parameter-elevation Regression on Independent Slopes Model (PRISM) data set as model input. We employed observed snow and streamflow data sets to guide modification of the snow and potential evapotranspiration components in the default model and to evaluate model performance. Based on various metrics and sensitivity tests, the modified model yields reasonably good simulations of seasonal snowpack in the West (range of bias of ±50 mm at 68% of 713 SNOTEL sites), the gradients and magnitudes of actual evapotranspiration, and runoff (median correlation of 0.83 and median Nash-Sutcliff efficiency of 0.6 between simulated and observed annual time series at 1427 USGS gage sites). The model generally performs well along the Pacific Coast, the high elevations of the Basin and Range and over the Midwest and East, but not as well over the dry areas of the Southwest and upper Plains regions due, in part, to the apportioning of direct versus delayed runoff. Sensitivity testing and application of the MWBM to simulate the future water balance at four National Parks when driven by 30 climate models from the Climate Model Intercomparison Program Phase 5 (CMIP5) demonstrate that the model is useful for evaluating first-order, climate driven hydrologic change on monthly and annual time scales. [ABSTRACT FROM AUTHOR]

We report a longitudinal, prospective, multicentre cohort study designed to measure the outcomes of gastrostomy tube feeding in children with cerebral palsy (CP). Fifty-seven children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) were assessed before gastrostomy placement, and at 6 and 12 months afterwards. Three-quarters of the children enrolled (43 of 57) had spastic quadriplegia; other diagnoses included mixed CP (6 of 57), hemiplegia (3 of 57), undiagnosed severe neurological impairment (3 of 57), ataxia (1 of 57), and extrapyramidal disorder (1 of 57). Only 7 of 57 (12%) could sit independently, and only 3 of 57 (5%) could walk unaided. Outcome measures included growth/anthropometry, nutritional intake, general health, and complications of gastrostomy feeding. At baseline, half of the children were more than 38D below the average weight for their age and sex when compared with the standards for typically-developing children. Weight increased substantially over the study period; the median weight z score increased from -3 before gastrostomy placement to -2.2 at 6 months and -1.6 at 12 months. Almost all parents reported a significant improvement in their child's health after this intervention and a significant reduction in time spent feeding. Statistically significant and clinically important increases in weight gain and subcutaneous fat deposition were noted. Serious complications were rare, with no evidence of an increase in respiratory complications. [ABSTRACT FROM AUTHOR]

The aim of this prospective cohort study was to evaluate the impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy (CP). Short-Form 36 version II was used to measure quality of life in carers of 57 Caucasian children with CP (28 females, 29 males; median age 4y 4mo, range 5mo to 17y 3mo) six and 12 months after insertion of a gastrostomy tube. Responses were calibrated against a normative dataset (Oxford Healthy Life Survey III). Six months after gastrostomy feeding was started, a substantial rise in mean domain scores for mental health, role limitations due to emotional problems, physical functioning, social functioning, and energy/vitality were observed. At 12 months after gastrostomy placement, carers reported significant improvements in social functioning, mental health, energy/vitality (mean increase >9.8 points;p<0.03), and in general health perception (mean increase 6.35 points;p=0.045) compared with results at baseline. Moreover, the values obtained for these domains at 12 months were not significantly different from the normal reference standard. Carers reported a significant reduction in feeding times, increased ease of drug administration, and reduced concern about their child's nutritional status. This study has demonstrated a significant, measurable improvement in the quality of life of carers after insertion of a gastrostomy feeding tube. [ABSTRACT FROM AUTHOR]