Environmental drivers of increased ecosystem respiration in a warming tundra.

Arctic and alpine tundra ecosystems are large reservoirs of organic carbon1,2. Climate warming may stimulate ecosystem respiration and release carbon into the atmosphere3,4. The magnitude and persistency of this stimulation and the environmental mechanisms that drive its variation remain uncertain5-7. This hampers the accuracy of global land carbon-climate feedback projections7,8. Here we synthesize 136 datasets from 56 open-top chamber in situ warming experiments located at 28 arctic and alpine tundra sites which have been running for less than 1 year up to 25 years. We show that a mean rise of 1.4 °C [confidence interval (CI) 0.9-2.0 °C] in air and 0.4 °C [CI 0.2-0.7 °C] in soil temperature results in an increase in growing season ecosystem respiration by 30% [CI 22-38%] (n = 136). Our findings indicate that the stimulation of ecosystem respiration was due to increases in both plant-related and microbial respiration (n = 9) and continued for at least 25 years (n = 136). The magnitude of the warming effects on respiration was driven by variation in warming-induced changes in local soil conditions, that is, changes in total nitrogen concentration and pH and by context-dependent spatial variation in these conditions, in particular total nitrogen concentration and the carbon:nitrogen ratio. Tundra sites with stronger nitrogen limitations and sites in which warming had stimulated plant and microbial nutrient turnover seemed particularly sensitive in their respiration response to warming. The results highlight the importance of local soil conditions and warming-induced changes therein for future climatic impacts on respiration.

Improving Accuracy of Administrative Data for Perforated Appendicitis Classification.

INTRODUCTION: Reliance on International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes may misclassify perforated appendicitis with resultant research, fiscal, and public health implications. We aimed to improve the accuracy of administrative data for perforated appendicitis classification relying on ICD-10-CM codes from 2015 to 2018. METHODS: We conducted a retrospective study of randomly sampled patients aged ≤18 years diagnosed with acute appendicitis from eight children's hospitals. Patients were identified using the Pediatric Health Information System, and true perforation status was determined by medical record review. We developed two algorithms by leveraging Pediatric Health Information System data elements and data mining (DM) approaches. The two developed algorithm performance was compared against algorithms that exclusively relied on ICD-10-CM codes using area under the curve and other measures. RESULTS: Of 1051 clinically validated encounters that were included, 383 (36.4%) patients were identified to have perforated appendicitis. The two algorithms developed using DM approaches primarily leveraged ICD-10-CM codes and length of stay. DM-developed algorithms had a significantly higher accuracy than algorithms relying exclusively on ICD-10-CM (P value < 0.01): sensitivity and specificity for DM-developed algorithms were 0.86-0.88 and 0.95-0.97, respectively, which were overall higher than algorithms that relied on only ICD-10-CM. CONCLUSIONS: This study provides an algorithm that can improve the accuracy of perforated appendicitis classification using commonly available elements in administrative data. We recommend that this algorithm is used in future appendicitis classification to ensure valid reporting, hospital-level benchmarking, and fiscal or public health assessments.

Controlled-Radical Polymerization of α-Lipoic Acid: A General Route to Degradable Vinyl Copolymers.

Here, we present the synthesis and characterization of statistical and block copolymers containing α-lipoic acid (LA) using reversible addition-fragmentation chain-transfer (RAFT) polymerization. LA, a readily available nutritional supplement, undergoes efficient radical ring-opening copolymerization with vinyl monomers in a controlled manner with predictable molecular weights and low molar-mass dispersities. Because lipoic acid diads present in the resulting copolymers include disulfide bonds, these materials efficiently and rapidly degrade when exposed to mild reducing agents such as tris(2-carboxyethyl)phosphine (Mn = 56 → 3.6 kg mol-1). This scalable and versatile polymerization method affords a facile way to synthesize degradable polymers with controlled architectures, molecular weights, and molar-mass dispersities from α-lipoic acid, a commercially available and renewable monomer.

Statistics for quantifying aging in time transfer system delays.

Residual time delays in time transfer systems such as two-way satellite time and frequency transfer (TWSTFT), or GPS carrier phase (GPSCP) change over time. A double difference such as TWSTFT-GPSCP provides information on the changes in the relative time delays of the two systems. These changes are referred to as aging or time dispersion. A first difference statistic, RMS time interval error, TIERMS, provides the RMS time dispersion. The time deviation statistic (TDEV) or a variation on the Allan deviation (ADEV), referred to here as ADEVS, provide information on the nature of the random fluctuations in aging. This paper describes analytical and Monte Carlo techniques used to estimate the aging (time dispersion) from TDEV or ADEVS statistics, and finds that the aging can be more than a factor of four larger than TDEV or ADEVS. The use of ADEVS is recommended over TDEV since it is sensitive to time drift.

Surgical outcomes and complications of bedside tracheostomy in the ICU for patients on ECMO.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is increasingly employed in the management of patients with severe cardiac and pulmonary dysfunction. Patients commonly require tracheostomy for ventilator liberation. Though bedside percutaneous tracheostomy is commonly performed, it has the potential for increased complications, both surgical and with the ECMO circuit. We examined surgical outcomes of bedside percutaneous tracheostomy in the ECMO population. METHODS: Patients were identified from an institutional database for bedside procedures. Demographics and data on complications were recorded. Descriptive statistics were calculated. RESULTS: 37 patients on ECMO at the time of tracheostomy were identified. Median age and BMI were 43.2 and 28.0, respectively. 33 patients (89%) were on VV ECMO, and 4 (11%) were on VA ECMO. All were on anticoagulation prior to tracheostomy, which was held for 4 h before and after the procedure in all cases. There were no procedure-related deaths or airway losses. No patients experienced periprocedural clotting events of their ECMO circuit or oxygenator within 24 h. 3 patients (8%) required reintervention (re-exploration or bronchoscopy) for bleeding. Four other patients (10%) had minor bleeding controlled with packing. One patient had pneumomediastinum which resolved without intervention, and one had an occlusion of their tracheostomy which was treated with tracheostomy exchange. CONCLUSIONS: Bedside percutaneous tracheostomy is feasible for patients on ECMO. Further study is needed to determine specific risk factors for complications and means to mitigate these. Bedside percutaneous tracheostomy may be considered as part of the management of patients on ECMO to help facilitate liberation from mechanical support.

Blinded Evaluation of Hyaluronic Acid Hand Filler Injections and Effects on First Impressions.

BACKGROUND: The hands are the second most common body part visible after the face. In the aging hand, the dorsum loses volume, becomes uneven, veins become more prominent, and there is an increase in spots and wrinkles. OBJECTIVE: To determine the effects of large-particle hyaluronic acid filler injection into the dorsal hand on first impressions. MATERIALS AND METHODS: Ten subjects underwent filler injections in the bilateral dorsal hands with large-particle hyaluronic acid filler. Photographs of the hands were taken at baseline and 2 weeks after the optimal correction result. A survey to evaluate first impressions was then completed by blinded evaluators on defined categories of perception. RESULTS: A total of 209 evaluators completed the first impression questionnaire. Overall, 10,032 individual assessments of first impressions were completed. There was a significant improvement in mean first impressions in all categories of perception and overall first impression scores. CONCLUSION: Cosmetic treatments to the hands is a growing field with the use of hyaluronic acid fillers to restore volume, decrease wrinkles, and improve the appearance of prominent veins. This study revealed an improvement in first impression scores in all categories following treatment with large-particle hyaluronic acid filler to the dorsal hands.

Evaluation of Selfies and Filtered Selfies and Effects on First Impressions.

BACKGROUND: Selfies and filtered selfies are becoming more prevalent throughout society and in the facial plastic surgery clinic. The term "Snapchat dysmorphia" has been used to describe patients seeking procedures to look like their selfie or filtered selfie. This is particularly frequent in the Millennial population, aged 22 to 37 years. OBJECTIVES: The authors sought to determine the effects on first impression from different photograph types: selfies, filtered selfies, a rear-facing smartphone camera, and a digital camera (DC). We hypothesize that the DC photographs will have the highest rated first impressions among evaluators despite the popularity of selfies and filtered selfies. METHODS: This study included 240 evaluators and 4 patients each completing the 4 different photograph types. The evaluators completed a survey rating first impression on various measures of success for each photograph type. RESULTS: A total of 960 first impressions were recorded for each of the 8 subscales, yielding 7680 individual assessments of first impression. The DC photograph was found to have the highest first impression scores among the 4 photograph types. There was no statistical difference between selfies and filtered selfies. The rear-facing smartphone camera received the lowest first impression scores. CONCLUSIONS: Our findings indicate that the standard DC photograph taken during a preoperative consultation has higher first impressions than selfies or filtered selfies. Although "Snapchat dysmorphia" may continue to be a growing trend in the near future, our findings provide important information to discuss with patients in the preoperative visit to set realistic expectations.

Implementation of General Surgery Care into a Student-Run Free Clinic.

BACKGROUND: Student-run free clinics (SRFCs) provide medical care to uninsured, and surgical issues are often outside the normal scope of care of these clinics. The Shade Tree Clinic (STC) is an SRFC serving 300 patients with complex medical conditions. This study describes the implementation and efficacy of a General Surgery Specialty Clinic in this setting. METHODS: This descriptive study examines the demographics and referral patterns of patients seen in two pilot Specialty Clinics and other patients evaluated for general surgical issues from December 2017 to January 2020. Providers were surveyed regarding their experience in clinic. RESULTS: Twenty patients were evaluated by six general surgeons during 22 separate encounters (n = 20). Nine patients were seen in two pilot Specialty Clinics for biliary colic, hernia, hemorrhoids, anal mass, toenail lesion, surgical weight loss, and venous insufficiency. Referrals from these clinics to affiliated Vanderbilt University Medical Center included six ultrasounds; referrals to vascular surgery and podiatry clinics; and referrals for laparoscopic cholecystectomy and anal mass excision. STC also directly referred eight patients for colonoscopies and five patients for major operations through primary care clinic. Hundred percent of care was cost-free to patients. Providers reported a median satisfaction score of five with the Specialty Clinics (Very Satisfied; [4, 5]). Hundred percent of providers felt that the concerns of patients were addressed. CONCLUSIONS: A surgery specialty clinic in the setting of an SRFC is an effective way to provide surgical care to underserved populations with the potential to reduce unplanned hospital utilization.

Orthogonal Cationic and Radical RAFT Polymerizations to Prepare Bottlebrush Polymers.

An orthogonal combination of cationic and radical RAFT polymerizations is used to synthesize bottlebrush polymers using two distinct RAFT agents. Selective consumption of the first RAFT agent is used to control the cationic RAFT polymerization of a vinyl ether monomer bearing a secondary dormant RAFT agent, which subsequently allows side-chain polymers to be grafted from the pendant RAFT agent by a radical-mediated RAFT polymerization of a different monomer, thus completing the synthesis of bottlebrush polymers. The high efficiency and selectivity of the cationic and radical RAFT polymerizations allow both polymerizations to be conducted in one-pot tandem without intermediate purification.

Characteristics and roles of extracellular vesicles released by epidermal keratinocytes.

Keratinocytes, which constitute 90% of the cells in the epidermis of the skin, have been demonstrated to communicate with other skin cells such as fibroblasts, melanocytes and immune cells through extracellular vesicles (EVs). This communication is facilitated by the enriched EV biomolecular cargo which regulates multiple biological processes within skin tissue, including cell proliferation, cell migration, anti-apoptosis, pigmentation transfer and extracellular matrix remodelling. This review will provide an overview of the current literature and advances in the field of keratinocyte-derived EV research with particular regard to the interactions and communication between keratinocytes and other skin cells, mediated by EVs and EV components. Importantly, this information may shed some light on the potential for keratinocyte-derived EVs in future biomedical studies.

Separation of Protactinium Employing Sulfur-Based Extraction Chromatographic Resins.

Protactinium-230 ( t1/2 = 17.4 d) is the parent isotope of 230U ( t1/2 = 20.8 d), a radionuclide of interest for targeted alpha therapy (TAT). Column chromatographic methods have been developed to separate no-carrier-added 230Pa from proton irradiated thorium targets and accompanying fission products. Results reported within demonstrate the use of novel sulfur bearing chromatographic extraction resins for the selective separation of protactinium. The recovery yield of 230Pa was 93 ± 4% employing a R3P═S type commercially available resin and 88 ± 4% employing a DGTA (diglycothioamide) containing custom synthesized extraction chromatographic resin. The radiochemical purity of the recovered 230Pa was measured via high purity germanium γ-ray spectroscopy to be >99.5% with the remaining radioactive contaminant being 95Nb due to its similar chemistry to protactinium. Measured equilibrium distribution coefficients for protactinium, thorium, uranium, niobium, radium, and actinium on both the R3P═S type and the DGTA resin in hydrochloric acid media are reported, to the best of our knowledge, for the first time.

Attenuated kallikrein-related peptidase activity disrupts desquamation and leads to stratum corneum thickening in human skin equivalent models.

BACKGROUND: Epidermal homeostasis is maintained through the balance between keratinocyte proliferation, differentiation and desquamation; however, human skin equivalent (HSE) models are known to differentiate excessively. In native tissue, proteases such as kallikrein-related peptidase (KLK) 5 and KLK7 cleave the extracellular components of corneodesmosomes; proteins corneodesmosin, desmocollin 1 and desmoglein 1, loosening the cellular connections and enabling desquamation. The actions of KLK7 are tightly controlled by protease inhibitors, skin-derived antileucoproteinase (SKALP) and lymphoepithelial Kazal-type-related inhibitor (LEKTI), which also inhibits KLK5, localizing protease activity to the stratum corneum. OBJECTIVES: To investigate the mechanisms that inhibit the desquamation cascade in HSE models. METHODS: Human skin tissue and HSE models were investigated using gene microarray, real-time polymerase chain reaction (PCR), immunohistochemistry and Western blot analysis to examine key components of the desquamation pathway. To elucidate proteolytic activity in HSEs and native skin, in situ and gel zymography was performed. RESULTS: Histological analysis indicated that HSE models form a well-organized epidermis, yet develop an excessively thick and compact stratum corneum. Gene microarray analysis revealed that the desquamation cascade was dysregulated in HSE models and this was confirmed using real-time PCR and immunohistochemistry. Immunohistochemistry and Western blot indicated overexpression of LEKTI and SKALP in HSEs. Although KLK7 was also highly expressed in HSEs, zymography indicated that protease activation and activity was lower than in native skin. CONCLUSIONS: These findings demonstrate that stratum corneum thickening is due to inhibited KLK5 and KLK7 activation and a subsequent lack of corneodesmosome degradation in the HSE model epidermis.

Synthesis and Crystal Structures of Volatile Neptunium(IV) ß-Diketonates.

Production of certified reference materials in support of domestic nuclear forensics programs require volatile precursors for introduction into electromagnetic isotopic separation instruments. ß-Diketone chelates of tetravalent actinides are known for their high volatility, but previously developed synthetic approaches require starting material (NpCl4) that is prohibitively difficult and hazardous to prepare. An alternative strategy was developed here that uses controlled potential electrolysis to reduce neptunium to the tetravalent state in submolar concentrations of hydrochloric acid. Four different ß-diketone ligands of varying degrees of fluorination were reacted with an aqueous solution of Np4+. Products of this reaction were characterized via X-ray diffraction and infrared spectroscopy, and were found to be neutral 8-coordinate complexes that adopt square antiprismatic crystal geometry. Synthesis of Np ß-diketonates by this approach circumvents the necessity of using NpCl4 in tetravalent Np coordination compound synthesis. The volatility of the complexes was assessed using thermogravimetric analysis, where the temperature of sublimation was determined to be in the range of 180° to 205 °C. The extent of fluorination did not appreciably alter the sublimation temperature of the complex. Thermal decomposition of these compounds was not observed during sublimation. High volatility and thermal stability of Np ß-diketonates make them ideal candidates for gaseous introduction into isotopic separation instruments.

Cost-effectiveness of pelvic exenteration for locally advanced malignancy.

BACKGROUND: The rising cost of healthcare is well documented. The purpose of this study was to determine the cost-effectiveness of pelvic exenteration (PE). METHODS: Consecutive patients referred for consideration of PE between 2008 and 2011 were recruited into a prospective non-randomized study that compared quality of life (QoL) between patients who did or did not undergo PE. Information on QoL and cost (in Australian dollars, AUD) was collected at baseline, during admission and up to 24 months after discharge. QoL data were converted into a utility-based measure. Quality-adjusted life-years (QALYs) were calculated. Bottom-up costing was performed. The incremental cost-effectiveness ratio (ICER) was calculated per life-year saved and per QALY. RESULTS: There were 174 patients with sufficient data for analysis. Of these, 139 underwent PE. R0 was achieved in 78·4 per cent of patients. The survival rate at 24 months after PE was 74·8 per cent compared with 43 per cent in those without exenteration (P = 0·001). Treatment costs were significantly higher for patients who had PE compared with those who did not (mean AUD 137 407 versus 79 174; P < 0·001). The ICER was AUD 124 147 (95 per cent c.i. 71 585 to 261 876) per life-year saved and AUD 227 330 (109 974 to 1 100 449) per QALY. Curative PE (R0) was found to be more cost-effective than non-curative PE (R1/R2), with an ICER of AUD 101 518 (60 105 to 200 428) versus 390 712 (74 368 to 82 256 739) per life-year saved. CONCLUSION: Treatment of advanced pelvic cancers is expensive regardless of the treatment intent. For a cost difference of only AUD 58 000 (€38 264), PE offers a chance of cure, and improves survival and QoL.

Neurology of the cryopyrin-associated periodic fever syndrome.

BACKGROUND AND PURPOSE: The cryopyrin-associated periodic fever syndrome (CAPS) is an autosomal dominant autoinflammatory disorder caused by mutations in the NLRP3 gene and is typified by recurrent episodes of systemic inflammation resulting in fever, urticarial rash and arthralgia. In addition to these systemic aspects, CAPS has multiple neurological manifestations. The largest case series to date is presented focusing on the neurological features of this disorder. METHODS: The case histories of a cohort of 38 UK patients with genetically proven CAPS who were treated with interleukin 1ß (IL-1ß) inhibition as part of a national treatment programme and underwent detailed neurological assessment were reviewed. RESULTS: Across the entire disease course neurological manifestations were present in 95% of patients; 84% had some form of headache; 66% sensorineural hearing loss; 60% myalgia; 34% papilloedema and 26% optic atrophy. Patients with the T348M mutation tended to have a more severe neurological phenotype with an earlier age of onset. Four patients had cerebrospinal fluid examination, three of whom had evidence of aseptic meningitis. There was a marked response to IL-1ß inhibition, which has revolutionized management of these patients (29/32 patients with headache responding). CONCLUSION: Neurological symptoms are extremely common in CAPS and these results highlight the importance of increasing awareness amongst neurologists, particularly as highly effective therapies are available.

Covalency-Driven Dimerization of Plutonium(IV) in a Hydroxamate Complex.

The reaction of formohydroxamic acid [NH(OH)CHO, FHA] with Pu(III) should result in stabilization of the trivalent oxidation state. However, slow oxidation to Pu(IV) occurs, which leads to formation of the dimeric plutonium(IV) formohydroxamate complex Pu2(FHA)8. In addition to being reductants, hydroxamates are also strong π-donor ligands. Here we show that formation of the Pu2(FHA)8 dimer occurs via covalency between the 5f orbitals on plutonium and the π* orbitals of FHA(-) anions, which gives rise to a broad and intense ligand-to-metal charge-transfer feature. Time-dependent density functional theory calculations corroborate this assignment.

Autosomal dominant polycystic kidney disease caused by somatic and germline mosaicism.

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder caused by loss of function mutations of PKD1 or PKD2 genes. Although PKD1 is highly polymorphic and the new mutation rate is relatively high, the role of mosaicism is incompletely defined. Herein, we describe the molecular analysis of ADPKD in a 19-year-old female proband and her father. The proband had a PKD1 truncation mutation c.10745dupC (p.Val3584ArgfsX43), which was absent in paternal peripheral blood lymphocytes (PBL). However, very low quantities of this mutation were detected in the father's sperm DNA, but not in DNA from his buccal cells or urine sediment. Next generation sequencing (NGS) analysis determined the level of this mutation in the father's PBL, buccal cells and sperm to be ∼3%, 4.5% and 10%, respectively, consistent with somatic and germline mosaicism. The PKD1 mutation in ∼10% of her father's sperm indicates that it probably occurred early in embryogenesis. In ADPKD cases where a de novo mutation is suspected because of negative PKD gene testing of PBL, additional evaluation with more sensitive methods (e.g. NGS) of the proband PBL and paternal sperm can enhance detection of mosaicism and facilitate genetic counseling.

High nucleotide diversity and limited linkage disequilibrium in Helicoverpa armigera facilitates the detection of a selective sweep.

Insecticides impose extreme selective pressures on populations of target pests and so insecticide resistance loci of these species may provide the footprints of 'selective sweeps'. To lay the foundation for future genome-wide scans for selective sweeps and inform genome-wide association study designs, we set out to characterize some of the baseline population genomic parameters of one of the most damaging insect pests in agriculture worldwide, Helicoverpa armigera. To this end, we surveyed nine Z-linked loci in three Australian H. armigera populations. We find that estimates of π are in the higher range among other insects and linkage disequilibrium decays over short distances. One of the surveyed loci, a cytochrome P450, shows an unusual haplotype configuration with a divergent allele at high frequency that led us to investigate the possibility of an adaptive introgression around this locus.

Ionothermal synthesis of tetranuclear borate clusters containing f- and p-block metals.

The reactions of simple oxides or halides of trivalent lanthanides and actinides or bismuth with boric acid in the ionic liquid 1-butyl-3-methylimidazolium chloride at 150 °C result in the formation and crystallization of a series of isomorphous tetranuclear borate clusters with the general formula M4B22O36(OH)6(H2O)13 (M = La, Ce, Pr, Nd, Sm, Eu, Gd, Pu, and Bi). These clusters do not assemble with trivalent cations smaller than Gd(3+), suggesting that the formation of the clusters is dictated by the size of the metal ion. The cations are found in cavities along the periphery of a cage assembled from the corner- and edge-sharing interactions of BO3 triangles and BO4 tetrahedra, yielding a complex chiral cluster. Both enantiomers cocrystallize. The metal ions are nonacoordinate, and their geometries are best described as distorted tridiminished icosahedra. This coordination environment is new for both Pu(3+) and Bi(3+). In addition to detailed structural information, UV/vis-NIR absorption and photoluminescence spectra are also provided.

Quality of life and other patient-reported outcomes following exenteration for pelvic malignancy.

BACKGROUND: Pelvic exenteration is highly radical surgery offering the only potential cure for locally advanced pelvic cancer. This study compared quality of life and other relevant patient-reported outcomes over 12 months for patients who did and those who did not undergo pelvic exenteration. METHODS: Consecutive patients referred for consideration of pelvic exenteration completed clinical and patient-reported outcome assessments at baseline, hospital discharge (exenteration patients only), and 1, 3, 6, 9 and 12 months. Outcomes included cancer-specific quality of life (Functional Assessment of Cancer Therapy - Colorectal; FACT-C), physical and mental health status (Short Form 36 version 2), psychological distress (Distress Thermometer), and pain (study-specific composite) scores. Linear mixed modelling compared trajectories between exenteration and no-exenteration groups. RESULTS: Among 182 patients, 148 (81.3 per cent) proceeded to exenteration. There were no baseline differences between the two groups. Among patients who had exenteration, the mean FACT-C score at baseline of 93.0 had reduced by 14·4 points at hospital discharge, but increased to 86·7 at 1 month after surgery and continued to improve, returning to baseline by 9 months. For patients in the no-exenteration group, FACT-C scores decreased between baseline and 1 month, increased slowly to 6 months and then began to decline at 9 months. There were few statistically or clinically significant differences in any patient-reported outcomes between the groups. CONCLUSION: Quality of life and related patient-reported outcomes improve rapidly after pelvic exenteration surgery. For 9 months after surgery, these outcomes are comparable with those of similar do patients who do not have surgery; thereafter, there is a decline in patients who do not have exenteration. Pelvic exenteration can be performed with acceptable quality of life and patient-reported outcomes.