Through the Looking Glass: Using the Lens of [SNS]-Pincer Ligands to Examine First-Row Metal Bifunctional Catalysts.

ConspectusHomogeneous catalysis is at the forefront of global efforts to innovate the synthesis of fine chemicals and achieve carbon-neutrality in energy applications. For decades, the push toward sustainable catalysis has focused on the development of first-row transition metal catalysts to supplant widespread use of precious metals. Metal-ligand cooperativity is an effective strategy to yield high-performing first-row metal molecular catalysts. Despite remarkable progress, state of the art catalysts often employ phosphorus-based ligands which are air-sensitive, potentially toxic, and on occasion offset the cost-savings of the metal. Thus, the development of simple and economical ligands composed of biomimetic donors should be a key focus that cannot be overlooked in the pursuit of sustainable catalyst candidates. This is an Account of our group's efforts to develop first-row transition metal complexes which use [SNS]-pincer ligands for bifunctional catalysis. We have synthesized two potentially tridentate ligands, one bearing an amido and two thioether donors [(SMeNSMe), L1] and one which includes thiolate, imine, and thioether donors [(SNSMe), L2], and used them as platforms upon which to explore the reaction pathways of first-row metals. The [SNS] ligand, L1, leads to formation of high-spin paramagnetic metal complexes of the type M(L1)2 in which the 6-membered ring thioether donor is hemilabile (M = Mn, Fe, Co). This allows Mn(L1)2 to function as a carbonyl hydroboration catalyst that operates by a novel hydride-free, inner-sphere reaction pathway. Exploring the reactivity of L2 with Fe and Ni revealed unique coordination chemistry and a variety of mono-, di-, tri-, and tetranuclear complexes enabled by bridging thiolates. Further studies showed L2 undergoes selective Caryl-S bond cleavage upon coordination to a metal with electron-rich phosphine donors, yielding a new (CNS)2- pincer ligand. The analogous reaction with L1 afforded a new (CNSMe)- pincer ligand via both Caryl-S and benzylic C-H bond cleavage. In an attempt to prepare Fe(L2)2, we obtained instead an Fe(N2S3) complex in which imine C-C bond formation affords a potentially hexadentate redox-active ligand. The Fe(N2S3) complex is a selective catalyst for hydroboration of aldehydes and appears to operate through a complicated mechanism. In contrast, a mechanistic study of Mn(L2)(CO)3-photocatalyzed dihydroboration of nitriles indicated that both the flexibility of the κ3-SNSMe ligand (fac- vs mer-coordination) and ability of Mn to undergo a spin-state change are required to access low energy barriers for this transformation. To effectively compare the reactivity of the thiolate vs amido donor, we prepared two Cu complexes, Cu(L1)(IPr) and Cu(L2)(IPr) [IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene], showing that, while both served as carbonyl hydroboration catalysts, only the amido complex was an effective catalyst for carbonyl hydrosilylation. In addition, complexes of the type Zn(L1)2, Zn(L2)2, and Zn(L1)(L2), were also effective for catalytic carbonyl hydroboration. While Zn(L1)(L2) was most active, catalyst speciation studies showed that each undergoes bifunctional catalyst activation to form a Zn bis(alkoxide) catalyst. Overall, our observations using [SNS] ligands with first-row transition metals show how the absence of traditional phosphine donors leads to different fundamental reactivity. Furthermore, this Account demonstrates the gap of knowledge which exists in understanding the reactivity of sulfur-based ligands to promote more widespread adoption of sustainable ligands.

Electron-Triggered Imine Coupling: Synthesis and Characterization of Three Redox States (0,-1,-2) of a Ni(N2 S2 ) Complex.

Metal imine-thiolate complexes, M(NS)2 are known to undergo imine C-C bond formation to give M(N2 S2 ) complexes (M=Co, Ni) containing a redox-active ligand. Although these transfor-mations are not typically quantitative, we demonstrate here that the one-electron reduction of a related Ni bis(imine-thiolate) complex affords the corresponding paramagnetic [Ni(N2 S2 )]- anion (2⋅- ) exclusively; subsequent oxidation with [Cp2 Fe]BF4 then affords a high yield of neutral 2 (Cp=η5 -cyclopentadienyl). Moreover, electrochemical studies indicate that a second one-electron reduction affords the diamagnetic dianion. Both anionic products were isolated and characterized by SC-XRD and their electronic structures were investigated by UV-vis spectro-electrochemistry, EPR and NMR spectroscopy, and DFT studies. These studies show that reduction proceeds primarily on the ligand, with (N2 S2 )4- containing both thiolate and ring-delocalized anions.

Motivation and context of concurrent stimulant and opioid use among persons who use drugs in the rural United States: a multi-site qualitative inquiry.

BACKGROUND: In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. METHODS: We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. RESULTS: We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. CONCLUSION: In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Nickel-Catalyzed Homologation of Vinylidene Difluoride (CH2═CF2): Selective ß-F vs ß-H Elimination.

Hydrofluoroolefins (HFOs) constitute the newest generation of fluorocarbon refrigerants and foam-blowing agents due to their reduced global warming potential vs their saturated analogues. To identify new synthetic routes to HFOs, we show that reactions of bulky Ni(0) phosphine and -NHC complexes with vinylidene difluoride (VF2) afford µ-fluoro-1,1,3-trifluorobut-3-enyl Ni complexes. Moreover, addition of triisopropylsilane allows for reductive elimination of the reduced product─2,4,4-trifluoro-1-butene─demonstrating the Ni-catalyzed hydrodefluorodimerization of VF2. Accompanying DFT calculations identify the T-shaped nickelacyclopentane intermediate that spontaneously undergoes selective intramolecular ß-F (vs ß-H) elimination.

Comparing B-H Bond Activation in NiIIX(NNN)-Catalyzed Nitrile Dihydroboration (X = Anionic N-, C-, O-, S-, or P-donor).

One of the key steps in many metal complex-catalyzed hydroboration reactions is B-H bond activation, which results in metal hydride formation. Anionic ligands that include multiple lone pairs of electrons, in cooperation with a metal center, have notable potential in redox-neutral B-H bond activation through metal-ligand cooperation. Herein, using an easily prepared NpyridineNimineNpyrrolide ligand (L2)-, a series of divalent NiIIX(NNN) complexes were synthesized, with X = bromide (2), phenoxide (3), thiophenoxide (4), 2,5-dimethylpyrrolide (5), diphenylphosphide (6), and phenyl (7). The complexes were characterized using 1H and 13C NMR spectroscopy, mass spectrometry, and X-ray crystallography and employed as precatalysts for nitrile dihydroboration. Superior activity of the phenoxy derivative (3) [vs thiophenoxy (4) or phenyl (7)] suggests that B-H bond activation occurs at the Ni-X (vs ligand Ni-Npyrrolide) bond. Furthermore, stoichiometric treatment of 2-7 with a nitrile showed no reaction, whereas stoichiometric reactions of 2-7 with pinacolborane (HBpin) gave the same Ni-H complex for 2, 3, and 5. Considering that only 2, 3, and 5 successfully catalyzed nitrile dihydroboration, we suggest that the catalytic cycle involves a conventional inner sphere pathway initiated by substrate insertion into Ni-H.

Fluorocarbon Refrigerants and their Syntheses: Past to Present.

This Review chronicles the progress made in the field of small fluorocarbon synthesis since their invention in the early 1930s by Thomas Midgley, Jr., and his coworkers, with special focus on their application as refrigerants, foam expansion agents, aerosol propellants, and precision solvents. Divided into four generations of C1-C4 halocarbons from CFCs through HCFCs, HFCs, and HFOs, the merits and challenges of each will be discussed in the context of market demands, as well as the evolution of industrial manufacturing methods. Vital transformations, such as exchange (Swarts) fluorination, hydrodehalogenation, dehydrohalogenation, and additions (Kharasch or Prins) will feature prominently and will be discussed in detail, as well as catalysts therefor. Of the myriad of fluorocarbons described herein, the models which have reached particular commercial significance (such as chlorodifluoromethane and 1,1,1,2-tetrafluoroethane) are given special consideration as flag-bearers for the generation to which they belong. Regulatory constraints to which this industry is bound will be outlined in brief, as well as an introduction to safety designations and nomenclature put forth by the American Society for Heating, Refrigerating, and Air-Conditioning Engineers (ASHRAE). This Review includes predominantly works which can only be found in the patent literature, but should be of equal interest to both academic and industrial practitioners of the art as it centers on fundamentals of organofluorine chemistry, which could equally be applied to the synthesis of larger molecules and building blocks for other applications.

Overlapping functions of YDA and MAPKKK3/MAPKKK5 upstream of MPK3/MPK6 in plant immunity and growth/development.

Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE3 (MAPK3 or MPK3) and MPK6 play important signaling roles in plant immunity and growth/development. MAPK KINASE4 (MKK4) and MKK5 function redundantly upstream of MPK3 and MPK6 in these processes. YODA (YDA), also known as MAPK KINASE KINASE4 (MAPKKK4), is upstream of MKK4/MKK5 and forms a complete MAPK cascade (YDA-MKK4/MKK5-MPK3/MPK6) in regulating plant growth and development. In plant immunity, MAPKKK3 and MAPKKK5 function redundantly upstream of the same MKK4/MKK5-MPK3/MPK6 module. However, the residual activation of MPK3/MPK6 in the mapkkk3 mapkkk5 double mutant in response to flg22 pathogen-associated molecular pattern (PAMP) treatment suggests the presence of additional MAPKKK(s) in this MAPK cascade in signaling plant immunity. To investigate whether YDA is also involved in plant immunity, we attempted to generate mapkkk3 mapkkk5 yda triple mutants. However, it was not possible to recover one of the double mutant combinations (mapkkk5 yda) or the triple mutant (mapkkk3 mapkkk5 yda) due to a failure of embryogenesis. Using the clustered regularly interspaced short palindromic repeats (CRISPR) - CRISPR-associated protein 9 (Cas9) approach, we generated weak, N-terminal deletion alleles of YDA, yda-del, in a mapkkk3 mapkkk5 background. PAMP-triggered MPK3/MPK6 activation was further reduced in the mapkkk3 mapkkk5 yda-del mutant, and the triple mutant was more susceptible to pathogen infection, suggesting YDA also plays an important role in plant immune signaling. In addition, MAPKKK5 and, to a lesser extent, MAPKKK3 were found to contribute to gamete function and embryogenesis, together with YDA. While the double homozygous mapkkk3 yda mutant showed the same growth and development defects as the yda single mutant, mapkkk5 yda double mutant and mapkkk3 mapkkk5 yda triple mutants were embryo lethal, similar to the mpk3 mpk6 double mutants. These results demonstrate that YDA, MAPKKK3, and MAPKKK5 have overlapping functions upstream of the MKK4/MKK5-MPK3/MPK6 module in both plant immunity and growth/development.

Nickel(II)-SNS Thiolate Complexes: Reactivity and Solution Dynamics.

Nickel coordination chemistry with a biomimetic thiolate-imine-thioether SNSMe ligand is accompanied by diverse reactivity and multidentate ligand dynamics. Reaction of Ni(acac)2 with 2 equiv of 2-(methylthio)-phenyl-benzothiazolidine (MPB) affords the bis(arylimino-phenylene-thiolate) complex Ni(κ2-SNSMe)2 (1; acac = acetylacetonate). Thermolysis of 1 in refluxing toluene is accompanied by imine C-C bond formation, yielding [Ni(N2S2)] (2) with a redox-active ligand. Protonation of 1 with NHTf2 at a low temperature released 1 equiv of MPB, yielding crystals of the dimeric dication {[Ni(µ-κ3-SNSMe)]2}(NTf2)2 (3; Tf = SO2CF3) in high yield. In contrast, the same reaction at room temperature gave also paramagnetic complexes {Ni[µ-Ni(κ3-SNSMe)2]2}(NTf2)2 (4) and {Ni[µ-Ni(κ3-SNSMe)2]3}(NTf2)2 (5) that feature coordination of two or three pseudo-octahedral, paramagnetic Ni(κ3-SNSMe)2 units to a central Ni(II) dication via thiolate bridges. Remarkably, dissolution of 3 in a variety of solvents, including weakly coordinating CH2Cl2, rapidly generates a mixture of 4 and Ni(NTf)2. Treatment of this mixture with Lewis bases L gave high yields of dimers {[Ni(µ-κ3-SNSMe)L]2}(NTf2)2 for L = CNXylyl (6a) and {[Ni(µ-κ3-SNSMe)]2(µ-dmpm)}(NTf2)2 (6b; dmpm = bis(dimethylphosphino)methane) or monomers [Ni(κ3-SNSMe)L](NTf2) for L = PMe3 (7a) and P(OMe)3 (7b). Addition of 2 equiv of the strong donor N-heterocyclic carbene ligand, IPr, to 3, however, led to thioether demethylation, affording neutral dithiolate complex Ni(κ3-SNS)(IPr) (8). Reaction products were characterized by NMR and mass spectrometry and complexes 1-5, 6a, 6b, 7a, and 8 by single-crystal X-ray diffraction.

Strategies and mechanisms of metal-ligand cooperativity in first-row transition metal complex catalysts.

The use of metal-ligand cooperation (MLC) by transition metal bifunctional catalysts has emerged at the forefront of homogeneous catalysis science. Specially designed ligands can serve a Lewis base or Lewis acid function, as an aromatization/dearomatization shuttle, or as an electron reservoir with reversible redox activity. This review encapsulates advances that have been made in this field over the last ten years, focusing exclusively on first-row transition metals, and highlighting significant contributions to mechanistic understanding.

Cardiomyocyte cell cycling, maturation, and growth by multinucleation in postnatal swine.

BACKGROUND: Rodent cardiomyocytes (CM) undergo mitotic arrest and decline of mononucleated-diploid population post-birth, which are implicated in neonatal loss of heart regenerative potential. However, the dynamics of postnatal CM maturation are largely unknown in swine, despite a similar neonatal cardiac regenerative capacity as rodents. Here, we provide a comprehensive analysis of postnatal cardiac maturation in swine, including CM cell cycling, multinucleation and hypertrophic growth, as well as non-CM cardiac factors such as extracellular matrix (ECM), immune cells, capillaries, and neurons. Our study reveals discordance in postnatal pig heart maturational events compared to rodents. METHODS AND RESULTS: Left-ventricular myocardium from White Yorkshire-Landrace pigs at postnatal day (P)0 to 6 months (6mo) was analyzed. Mature cardiac sarcomeric characteristics, such as fetal TNNI1 repression and Cx43 co-localization to cell junctions, were not evident until P30 in pigs. In CMs, appreciable binucleation is observed by P7, with extensive multinucleation (4-16 nuclei per CM) beyond P15. Individual CM nuclei remain predominantly diploid at all ages. CM mononucleation at ~50% incidence is observed at P7-P15, and CM mitotic activity is measurable up to 2mo. CM cross-sectional area does not increase until 2mo-6mo in pigs, though longitudinal CM growth proportional to multinucleation occurs after P15. RNAseq analysis of neonatal pig left ventricles showed increased expression of ECM maturation, immune signaling, neuronal remodeling, and reactive oxygen species response genes, highlighting significance of the non-CM milieu in postnatal mammalian heart maturation. CONCLUSIONS: CM maturational events such as decline of mononucleation and cell cycle arrest occur over a 2-month postnatal period in pigs, despite reported loss of heart regenerative potential by P3. Moreover, CMs grow primarily by multinucleation and longitudinal hypertrophy in older pig CMs, distinct from mice and humans. These differences are important to consider for preclinical testing of cardiovascular therapies using swine, and may offer opportunities to study aspects of heart regeneration unavailable in other models.

Physics of Nuclei: Key Role of an Emergent Symmetry.

We show through first-principles nuclear structure calculations that the special nature of the strong nuclear force determines highly regular patterns heretofore unrecognized in nuclei that can be tied to an emergent approximate symmetry. This symmetry is ubiquitous and mathematically tracks with a symplectic symmetry group. This, in turn, has important implications for understanding the physics of nuclei: we find that nuclei are made of only a few equilibrium shapes, deformed or not, with associated vibrations and rotations. It also opens the path for ab initio large-scale modeling of open-shell intermediate-mass nuclei without the need for renormalized interactions and effective charges.

Selective Copper Complex-Catalyzed Hydrodefluorination of Fluoroalkenes and Allyl Fluorides: A Tale of Two Mechanisms.

The transition to more economically friendly small-chain fluorinated groups is leading to a resurgence in the synthesis and reactivity of fluoroalkenes. One versatile method to obtain a variety of commercially relevant hydrofluoroalkenes involves the catalytic hydrodefluorination (HDF) of fluoroalkenes using silanes. In this work it is shown that copper hydride complexes of tertiary phosphorus ligands (L) can be tuned to achieve selective multiple HDF of fluoroalkenes. In one example, HDF of the hexafluoropropene dimer affords a single isomer of heptafluoro-2-methylpentene in which five fluorines have been selectively replaced with hydrogens. DFT computational studies suggest a distinct HDF mechanisms for L2CuH (bidentate or bulky monodentate phosphines) and L3CuH (small cone angle monodentate phosphines) catalysts, allowing for stereocontrol of the HDF of trifluoroethylene.

Discharge properties of morphologically identified vestibular neurons recorded during horizontal eye movements in the goldfish.

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (eIIhI) or vice versa (eIhII). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant eIIhI subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in eIhII cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network. NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi.

Improving the nutritional intake of hospital patients: how far have we come? A re-audit.

BACKGROUND: Malnutrition affects up to 33.6% of hospitalised patients, with consequences that are detrimental for both patients and healthcare providers. In 2015, an audit demonstrated inadequate nutritional provision and consumption by hospitalised patients, comprising a major risk factor for malnutrition. This re-audit evaluates whether patients are meeting recommended energy and protein standards and estimated individual requirements, subsequent to food service improvements since 2015. METHODS: Patients (n = 111) were included from a South West hospital, and Malnutrition Universal Screening Tool scores (MUST) categorised patients as 'nutritionally well' (MUST 0) or 'nutritionally vulnerable' (MUST ≥ 1). Individual energy and protein requirements were estimated using weight-based equations. Nutritional intakes were assessed via 24-h dietary recall and compared against the British Dietetic Association's Nutrition and Hydration Digest standards, as well as estimated individual requirements. RESULTS: In total, the Digest standards for energy and protein were met by 35% and 63% of patients respectively, which is an increase of 19% and 36% since 2015. 'Nutritionally well' patients were more likely to meet nutrient standards for protein (62%) than estimated individual requirements (30%) (P ≤ 0.001). 'Nutritionally vulnerable' patients were more likely to meet estimated individual requirements for energy (60%) than the Digest standards (30%) (P = 0.047). CONCLUSIONS: The proportion of patients meeting the Digest standards has increased considerably following numerous food service changes. Nutritional training for housekeepers, energy/protein-dense snacks and drinks, and fortified dietary items may further increase nutritional intakes. Additionally, as a result of discrepancies between the Digest standards and individual estimated requirements, more research is required to identify the most appropriate auditing standards that reflect best practice.

Effects of dietary antioxidants and environmental stressors on immune function and condition in Lithobates (Rana) sylvaticus.

The negative effects of abiotic and biotic stressors on animal condition, physiology, behaviour, and fitness have become increasingly recognized, making it critical to understand how these may be mitigated, such as through diet. When consumed, dietary antioxidants (secondary metabolites produced by plants) provide protection from oxidative damage that can result from exposure to stressors. We examined the effects of dietary antioxidants (ß-carotene and vitamin E) on the ability of Lithobates sylvaticus (wood frog) tadpoles to overcome the detrimental effects imposed by two common environmental stressors - exposure to the herbicide atrazine or infection by a pathogenic helminth parasite (Echinostoma trivolvis). Tadpoles which were fed high concentrations of either vitamin E or ß-carotene had a greater immune response compared to those given trace diets of either compound as measured by circulating white blood cells and a phytohemaglutination assay (PHA). Similarly, tadpoles in the herbicide and parasitism treatments that were given trace antioxidant diets had significant weight loss, whereas those consuming high levels of vitamin E or ß-carotene did not. Our results suggest that dietary antioxidants, specifically ß-carotene and vitamin E, have a positive effect on tadpole immune systems and overall condition that likely allows them to better cope with natural stressors, with potential implications for their foraging behaviour.

Investigation of thermally induced damage to surrounding nerve tissue when using curettage and cementation of long bone tumours, modelled in cadaveric porcine femurs.

INTRODUCTION: Curettage with cement augmentation is a technique used in the treatment of bone tumours. Thermal energy released during the cement polymerisation process can damage surrounding tissues. This study aims to record temperature changes at various sites on and around bone during the cementing process. We hypothesised that adjacent structures, such as the radial nerve, may be threatened by this process in the clinical setting. MATERIALS AND METHODS: Using 18 porcine femurs as a model of the human humerus, we used thermocouples and a thermal imaging camera to measure changes in temperature during the cementing process. Fractures were created in nine samples to establish whether a discontinuity of the cortex had an effect on thermal conduction. RESULTS: Significantly higher temperatures were recorded in samples with a fracture compared to those without a fracture. The site overlying the centre of the cement bolus (hypothetical site of the radial nerve) demonstrated higher temperatures than all other sites on the same cortex. When considering the radial nerve site, over half the samples demonstrated temperatures exceeding 47 °C for over a minute. When a threshold of 50 °C for more than 30 s was considered, three samples without a fracture exceeded this value compared to two with a fracture. CONCLUSION: The temperatures recorded were sufficient to cause damage to neural tissue. Limiting thermal exposure to soft tissues is recommended. Increased attention is required when using larger cement boluses, or where bone quality is poor or a fracture, iatrogenic or preexisting, is present.

Early Supported Discharge for patients with febrile neutropenia - Experience at a large district hospital in the UK.

Neutropenic sepsis can be life threatening, with mortality 2-21%. The heterogeneity of patients referred with "suspected neutropenic sepsis" has led to strategies being developed to risk-stratify patients and identify those with a low risk of septic complications that could be managed in the outpatient setting, such as The Multinational Association for Supportive Care in Cancer score (MASCC). Outcomes for patients referred with suspected neutropenic sepsis were assessed before and after use of MASCC guided early-supported discharge. 50/123 (41%) patients over 24 months were eligible for early-supported discharge. 26/50 patients had same-day discharge, 14 had overnight admission, 8 stayed 2 nights and 2 stayed 3 nights. Patients received on average 2 follow-up telephone consultations. There were 5 readmissions (10%) and no adverse events. In comparison group; 8 patients over 3-months would have been suitable, potentially saving 40 bed-days. This shows MASCC guided early-supported discharge is safe and cost-effective.

Maize Carbohydrate partitioning defective1 impacts carbohydrate distribution, callose accumulation, and phloem function.

Plants synthesize carbohydrates in photosynthetic tissues, with the majority of plants transporting sucrose to non-photosynthetic tissues to sustain growth and development. While the anatomical, biochemical, and physiological processes regulating sucrose long-distance transport are well characterized, little is known concerning the genes controlling whole-plant carbohydrate partitioning. To identify loci influencing carbon export from leaves, we screened mutagenized maize plants for phenotypes associated with reduced carbohydrate transport, including chlorosis and excessive starch and soluble sugars in leaves. Carbohydrate partitioning defective1 (Cpd1) was identified as a semi-dominant mutant exhibiting these phenotypes. Phloem transport experiments suggested that the hyperaccumulation of starch and soluble sugars in the Cpd1/+ mutant leaves was due to inhibited sucrose export. Interestingly, ectopic callose deposits were observed in the phloem of mutant leaves, and probably underlie the decreased transport. In addition to the carbohydrate hyperaccumulation phenotype, Cpd1/+ mutants overaccumulate benzoxazinoid defense compounds and exhibit increased tolerance when attacked by aphids. However, double mutant studies between Cpd1/+ and benzoxazinoid-less plants indicate that the ectopic callose and carbon hyperaccumulation are independent of benzoxazinoid production. Based on the formation of callose occlusions in the developing phloem, we hypothesize that the cpd1 gene functions early in phloem development, thereby impacting whole-plant carbohydrate partitioning.

High-intensity focused ultrasound in the treatment of breast fibroadenomata (HIFU-F trial).

BACKGROUND: High-intensity focussed ultrasound (HIFU) is a non-invasive ablative technique utilising the application of high frequency ultrasound (US) pressure waves to cause tissue necrosis. This emerging technology is currently limited by prolonged treatment times. The aim of the HIFU-F trial was to perform circumferential HIFU treatment as a means of shortening treatment times. METHODS: A prospective trial was set up to treat 50 consecutive patients ≥18 years of age. Eligible patients possessed symptomatic fibroadenomata, visible on US. Patients ≥25 years of age required histological confirmation of the diagnosis. Primary outcome measures were reduction in treatment time, reduction in volume on US after 12 months and complication rates. RESULTS: HIFU treatment was performed in 51 patients (53 treatments) with a mean age of 29.8 years (SD 7.2 years) and a diameter of 2.6 cm (SD 1.4 cm). Circumferential ablation reduced treatment times by an estimated 19.9 min (SD 25.1 min), which is a 29.4% (SD 15.2%) reduction compared with whole lesion ablation. Volume reduction of 43.2% (SD 35.4%; p < 0.005, paired t-test) was observed on US at 12 months post-treatment. Local complications completely resolved at 1 month apart from skin hyper-pigmentation, which persisted in nine cases at three months, six cases at 6 months and six at 12 months. CONCLUSION: Circumferential HIFU treatment for breast fibroadenomata is feasible to reduce both lesion size and treatment time. HIFU is a non-invasive alternative technique for the treatment of breast fibroadenomata. ISRCTN registration: 76622747.

A comparison of paternity data and relative testes size as measures of level of sperm competition in the Hominoidea.

OBJECTIVES: The phrase "level of sperm competition" is used only vaguely in the primate literature. There is also little distinction between the important elements of frequency and intensity of sperm competition, largely because the two current forms of measurement (socio-sexual system and relative testes size) are both proxies which allow neither precision nor fine distinctions. Both measures have critics, socio-sexual system in particular being branded subjective, misleading, and changeable. Testes size is considered the more reliable despite its validation resting on correlations with the other, less reliable, proxy. Recently, genetic paternity studies have been mooted to provide a potentially superior third measure of sperm competition but so far lack a formal interpretive framework. Here we use the published and relatively comprehensive genetic field studies of the Hominoidea to develop such a framework. MATERIALS AND METHODS: Formulae are derived to convert paternity data into a direct measure of the frequency, intensity, and overall level of sperm competition. We then compare these measures with relative testes size at the study, species, and phylogenetic levels. RESULTS: A significant correlation between level of sperm competition and relative testes size was obtained at each level. These correlations provide independent support for the continuing use of testes size as a proxy measure when such a measure is sufficient. However, they also suggest that paternity data and our formulae yield a viable alternative measure. DISCUSSION: This alternative measure based on paternity data has a number of advantages. Not only is it a potentially direct measure of the level of sperm competition but it also allows the roles of frequency and intensity to be studied separately when of interest.