Observation-derived 2010-2019 trends in methane emissions and intensities from US oil and gas fields tied to activity metrics.

The United States is the world's largest oil/gas methane emitter according to current national reports. Reducing these emissions is a top priority in the US government's climate action plan. Here, we use a 2010 to 2019 high-resolution inversion of surface and satellite observations of atmospheric methane to quantify emission trends for individual oil/gas production regions in North America and relate them to production and infrastructure. We estimate a mean US oil/gas methane emission of 14.8 (12.4 to 16.5) Tg a-1 for 2010 to 2019, 70% higher than reported by the US Environmental Protection Agency. While emissions in Canada and Mexico decreased over the period, US emissions increased from 2010 to 2014, decreased until 2017, and rose again afterward. Increases were driven by the largest production regions (Permian, Anadarko, Marcellus), while emissions in the smaller production regions generally decreased. Much of the year-to-year emission variability can be explained by oil/gas production rates, active well counts, and new wells drilled, with the 2014 to 2017 decrease driven by reduction in new wells and the 2017 to 2019 surge driven by upswing of production. We find a steady decrease in the oil/gas methane intensity (emission per unit methane gas production) for almost all major US production regions. The mean US methane intensity decreased from 3.7% in 2010 to 2.5% in 2019. If the methane intensity for the oil/gas supply chain continues to decrease at this pace, we may expect a 32% decrease in US oil/gas emissions by 2030 despite projected increases in production.

Observed changes in China's methane emissions linked to policy drivers.

China is set to actively reduce its methane emissions in the coming decade. A comprehensive evaluation of the current situation can provide a reference point for tracking the country's future progress. Here, using satellite and surface observations, we quantify China's methane emissions during 2010-2017. Including newly available data from a surface network across China greatly improves our ability to constrain emissions at subnational and sectoral levels. Our results show that recent changes in China's methane emissions are linked to energy, agricultural, and environmental policies. We find contrasting methane emission trends in different regions attributed to coal mining, reflecting region-dependent responses to China's energy policy of closing small coal mines (decreases in Southwest) and consolidating large coal mines (increases in North). Coordinated production of coalbed methane and coal in southern Shanxi effectively decreases methane emissions, despite increased coal production there. We also detect unexpected increases from rice cultivation over East and Central China, which is contributed by enhanced rates of crop-residue application, a factor not accounted for in current inventories. Our work identifies policy drivers of recent changes in China's methane emissions, providing input to formulating methane policy toward its climate goal.

Very large fluxes of methane measured above Bolivian seasonal wetlands.

Methane (CH4) mole fractions from the large semiseasonal Llanos de Moxos wetlands (∼70,000 km2) in northern Bolivia were measured by aircraft flights and ground sampling during early March 2019 (late wet season). Daily fluxes of CH4 determined from the measurements using box models and inverse modeling were between 168 (± 50) and 456 (± 145) mg CH4⋅m-2⋅d-1 for the areas overflown, very high compared with those of previous Amazon basin studies. If the seasonality of the CH4 emissions is comparable to other parts of the Amazon Basin, the region could contribute as much as 8% of annual Amazonian CH4 emissions.

Tropical methane emissions explain large fraction of recent changes in global atmospheric methane growth rate.

Large variations in the growth of atmospheric methane, a prominent greenhouse gas, are driven by a diverse range of anthropogenic and natural emissions and by loss from oxidation by the hydroxyl radical. We used a decade-long dataset (2010-2019) of satellite observations of methane to show that tropical terrestrial emissions explain more than 80% of the observed changes in the global atmospheric methane growth rate over this period. Using correlative meteorological analyses, we show strong seasonal correlations (r = 0.6-0.8) between large-scale changes in sea surface temperature over the tropical oceans and regional variations in methane emissions (via changes in rainfall and temperature) over tropical South America and tropical Africa. Existing predictive skill for sea surface temperature variations could therefore be used to help forecast variations in global atmospheric methane.

The added value of satellite observations of methane forunderstanding the contemporary methane budget.

Surface observations have recorded large and incompletely understood changes to atmospheric methane (CH4) this century. However, their ability to reveal the responsible surface sources and sinks is limited by their geographical distribution, which is biased towards the northern midlatitudes. Data from Earth-orbiting satellites designed specifically to measure atmospheric CH4 have been available since 2009 with the launch of the Japanese Greenhouse gases Observing SATellite (GOSAT). We assess the added value of GOSAT to data collected by the US National Oceanic and Atmospheric Administration (NOAA), which have been the lynchpin for knowledge about atmospheric CH4 since the 1980s. To achieve that we use the GEOS-Chem atmospheric chemistry transport model and an inverse method to infer a posteriori flux estimates from the NOAA and GOSAT data using common a priori emission inventories. We find the main benefit of GOSAT data is from its additional coverage over the tropics where we report large increases since the 2014/2016 El Niño, driven by biomass burning, biogenic emissions and energy production. We use data from the European TROPOspheric Monitoring Instrument to show how better spatial coverage and resolution measurements allow us to quantify previously unattainable diffuse sources of CH4, thereby opening up a new research frontier. This article is part of a discussion meeting issue 'Rising methane: is warming feeding warming? (part 1)'.

The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines.

The design and development of the first asymmetric aza-silyl-Prins reaction is reported, giving rise to valuable and diverse piperidines and pipecolic acid derivatives in both high yields and as single enantiomers. The creation of a novel chiral auxiliary-homoallylic amine for the aza-silyl-Prins reaction is essential to its success.

Atmospheric observations show accurate reporting and little growth in India's methane emissions.

Changes in tropical wetland, ruminant or rice emissions are thought to have played a role in recent variations in atmospheric methane (CH4) concentrations. India has the world's largest ruminant population and produces ~ 20% of the world's rice. Therefore, changes in these sources could have significant implications for global warming. Here, we infer India's CH4 emissions for the period 2010-2015 using a combination of satellite, surface and aircraft data. We apply a high-resolution atmospheric transport model to simulate data from these platforms to infer fluxes at sub-national scales and to quantify changes in rice emissions. We find that average emissions over this period are 22.0 (19.6-24.3) Tg yr-1, which is consistent with the emissions reported by India to the United Framework Convention on Climate Change. Annual emissions have not changed significantly (0.2 ± 0.7 Tg yr-1) between 2010 and 2015, suggesting that major CH4 sources did not change appreciably. These findings are in contrast to another major economy, China, which has shown significant growth in recent years due to increasing fossil fuel emissions. However, the trend in a global emission inventory has been overestimated for China due to incorrect rate of fossil fuel growth. Here, we find growth has been overestimated in India but likely due to ruminant and waste sectors.India's methane emissions have been quantified using atmospheric measurements to provide an independent comparison with reported emissions. Here Ganesan et al. find that derived methane emissions are consistent with India's reports and no significant trend has been observed between 2010-2015.

Fenoldopam to prevent acute kidney injury after major surgery-a systematic review and meta-analysis.

BACKGROUND: Acute kidney injury (AKI) after surgery is associated with increased mortality and healthcare costs. Fenoldopam is a selective dopamine-1 receptor agonist with renoprotective properties. We conducted a systematic review and meta-analysis of randomised controlled trials comparing fenoldopam with placebo to prevent AKI after major surgery. METHODS: We searched EMBASE, PubMed, meta-Register of randomised controlled trials and Cochrane CENTRAL databases for trials comparing fenoldopam with placebo in patients undergoing major surgery. The primary outcome was incidence of new AKI. Secondary outcomes were requirement for renal replacement therapy and hospital mortality. RESULTS: Eighty-three publications were screened; 23 studies underwent full data extraction and scoring. Six trials were suitable for inclusion in the data synthesis (total of 507 subjects undergoing cardiovascular surgery, partial nephrectomy, liver transplant surgery). Five studies were rated at high risk of bias. Data on post-operative incidence of AKI were available in five of the six trials (total of 471 patients) but definitions of AKI varied between studies. Of the 238 patients receiving fenoldopam, 45 (18.9%) developed AKI compared to 62 (26.6%) of the 233 patients who received placebo (p = 0.004, I (2) = 0 %; random-effects model odds ratio 0.46, 95% confidence interval 0.27-0.79). In patients treated with fenoldopam, there was no difference in renal replacement therapy (n = 478; p = 0.11, I (2) = 47%; fixed-effect model odds ratio 0.27, 95% confidence interval 0.06-1.19) or hospital mortality (p = 0.60, I (2) = 0 %; fixed-effect model odds ratio 1.0, 95% confidence interval 0.14-7.37). CONCLUSIONS: In this analysis, peri-operative treatment with fenoldopam was associated with a significant reduction in post-operative AKI but it had no impact on renal replacement therapy or hospital mortality. Equipoise remains for further large trials in this area since the studies were conducted in three types of surgery, the majority of studies were rated at high risk of bias and the criteria for AKI varied between trials.

Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment.

INTRODUCTION: Obstructive sleep apnoea (OSA) is common in obesity and is associated with cardiovascular and metabolic complications. Continuous positive airway pressure (CPAP) in OSA may lead to physiological changes reflected in the urinary proteome. The aim of this study was to characterise the urinary proteome in severely obese adult subjects with OSA who were receiving CPAP compared with severely obese subjects without OSA. METHODS: Severely obese subjects with and without OSA were recruited. Subjects with OSA were receiving CPAP. Body composition and blood pressure measurements were recorded. Urinary samples were analysed by Capillary Electrophoresis-Mass Spectrometry (CE-MS). RESULTS: Twenty-seven subjects with OSA-on-CPAP (age 49±7years, BMI 43±7 kg/m(2)) and 25 controls without OSA (age 52±9years, BMI 39±4 kg/m(2)) were studied. Age and BMI were not significantly different between groups. Mean CPAP use for OSA patients was 14.5±1.0 months. Metabolic syndrome was present in 14(52%) of those with OSA compared with 6(24%) of controls (p=0.039). A urinary proteome comprising 15 peptides was identified showing differential expression between the groups (p<0.01). Although correction for multiple testing did not reach significance, sequences were determined for 8 peptides demonstrating origins from collagens, fibrinogen beta chain and T-cadherin that may be associated with underlying cardiovascular disease mechanisms in OSA. CONCLUSIONS: The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA.

Serum urate and obstructive sleep apnoea in severe obesity.

Obstructive sleep apnoea (OSA) may increase the risk of hyperuricaemia and predispose to gout. The evidence for the effects of OSA on serum urate in severe obesity is limited. This study investigated whether OSA was associated with serum urate in severe obesity and whether continuous positive airway pressure (CPAP) treatment was associated with a fall in urate. Severely obese subjects without known OSA or gout were recruited. Baseline assessments included urate, metabolic parameters, spirometry and overnight polysomnography. OSA patients were initially naive to treatment and were offered CPAP. At follow-up, change in urate was compared between CPAP-treated and non-CPAP-treated subjects. A high urate was defined as greater than the median. Logistic regression was performed to identify associations between (1) OSA and high urate at baseline and (2) use of CPAP and change in urate at follow-up. In total, 92 subjects were recruited (61 (66%) OSA and 31 (34%) non-OSA). Median urate was 345 µmol/L. OSA was associated with high urate in females at baseline after adjusting for confounders (adjusted odds ratio ORadj = 10.2; 95% CI: 1.1, 93.5). At follow-up (14 months), 58 subjects (28 on CPAP and 30 not on CPAP) were reassessed. CPAP was significantly associated with a fall to a low urate category at follow-up ( = 0.017). Regression revealed a trend for a fall in urate category in the CPAP-treated group (ORadj = 9.3; 95% CI: 0.8, 97). Serum urate is associated with OSA in severely obese females and CPAP may reduce levels in patients with OSA. There may be a need to consider and assess for OSA in obese patients with hyperuricaemia and recurrent attacks of gout.

Effect of CPAP on arterial stiffness in severely obese patients with obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) may independently increase cardiovascular risk in obesity. Although there is evidence that arterial stiffness is altered in OSA, knowledge of these effects with continuous positive airway pressure (CPAP) in severe obesity (body mass index (BMI) ≥ 35 kg/m(2)) is limited. This study aimed to explore how arterial stiffness, as measured by the augmentation index (Aix), changed in severely obese patients with OSA who were treated with CPAP and in patients without OSA. METHODS: Forty-two patients with severe obesity-22 with OSA, 20 without OSA-were recruited at baseline and followed-up after a median of 13.5 months. Pulse wave analysis (PWA) was performed using applanation tonometry at the radial artery to measure augmentation index (Aix), augmentation pressure (AP) and subendocardial viability ratio (SEVR). Cardiovascular parameters and body composition were also measured. RESULTS: There were significant improvements in Aix, AP (both P < 0.001) and SEVR (P = 0.021) in OSA patients on CPAP compared with subjects without OSA. Epworth scores (P < 0.001), systolic (P < 0.001) and mean arterial pressures (P = 0.002) improved with CPAP. Regression showed that CPAP was significantly associated with change in arterial stiffness from baseline. However, patients with OSA on CPAP continued to have increased arterial stiffness (Aix) (P < 0.001), AP (P = 0.028) and reduced SEVR (P = 0.002) relative to non-OSA patients. CONCLUSION: Although sleepiness and blood pressure improve with CPAP in severe obesity, CPAP alone is not sufficient to modify PWA measures to levels comparable with non-OSA patients. This supports a need for a multifaceted approach when managing cardiovascular risk in patients with severe obesity and obstructive sleep apnoea receiving CPAP therapy.

Urinary proteomics in obstructive sleep apnoea and obesity.

BACKGROUND: Obstructive sleep apnoea (OSA) is a common complication of obesity and can have a substantial negative impact on a patient's quality of life and risk of cardiovascular disease. The aim of this case-control study was to undertake discovery profiling of urinary peptides using capillary electrophoresis-mass spectrometry (CE-MS) in obese subjects with and without OSA, without a history of coronary artery disease. MATERIALS AND METHODS: Urinary samples were analysed by CE-MS. Body composition and blood pressure measurements were recorded. Overnight polysomnography was conducted to confirm or refute OSA. OSA patients were naïve to continuous positive airway pressure treatment. RESULTS: Sixty-one subjects with OSA (age 47 ± 9 years, BMI 43 ± 8 kg/m(2)) and 31 controls (age 49 ± 10 years, BMI 40 ± 5 kg/m(2)) were studied; P = ns for age and BMI. Apnoea-hypopnoea Index was higher in patients with OSA (24 ± 18·6) than controls without OSA (non-OSA) (2·6 ± 1·1; P < 0·0001). Metabolic syndrome was present in 35 (57%) of those with OSA compared with 4 (13%) of controls (P < 0·0001). Twenty-four polypeptides were candidates for differential distribution (P < 0·01), although these differences did not reach significance after multiple testing. Sequences were determined for eight peptides demonstrating origins from collagens and fibrinogen alpha. CONCLUSIONS: In this study, we report for the first time, urinary proteomic profile analyses using CE-MS in OSA and non-OSA obese groups. The differences in urinary proteomic profiles prior to adjustment for multiple testing, with increased metabolic syndrome in obese OSA subjects, suggest that there may be a role for CE-MS in characterising urinary profiles in severely obese populations with OSA.

Obstructive sleep apnea is associated with increased arterial stiffness in severe obesity.

Obstructive sleep apnea is associated with obesity and metabolic syndrome, leading to greater cardiovascular risk. Severely obese patients with obstructive sleep apnea may still be at risk of adverse health outcomes, even without previous cardiovascular disease. Pulse wave analysis non-invasively measures peripheral pulse waveforms and derives measures of haemodynamic status, including arterial stiffness, augmentation pressure and subendocardial viability ratio. We hypothesized that the presence of obstructive sleep apnea in severe obesity, even in the absence of an antecedent history of cardiovascular disease, would affect measurements derived from pulse wave analysis. Seventy-two severely obese adult subjects [obstructive sleep apnea 47 (body mass index 42 ± 7 kg m(-2) ), without obstructive sleep apnea (non-OSA) 25 (body mass index 40 ± 5 kg m(-2) )] were characterised using anthropometric, respiratory and cardio-metabolic parameters. Groups were similar in age, body mass index and gender. More subjects with obstructive sleep apnea had metabolic syndrome [obstructive sleep apnea 60%, without obstructive sleep apnea (non-OSA) 12%]. Those with obstructive sleep apnea had greater arterial stiffness, augmentation pressure and decreased subendocardial viability ratio (all P < 0.001), with significantly higher systolic (P = 0.003), diastolic (P = 0.04) and mean arterial pressures (P = 0.004) than patients without obstructive sleep apnea (non-OSA). Arterial stiffness correlated with mean arterial blood pressure (P = 0.003) and obstructive sleep apnea severity (apnea-hypopnea index; P < 0.001). apnea-hypopnea index significantly predicted arterial stiffness in multiple regression analysis, but components of the metabolic syndrome did not. Thus, patients with obstructive sleep apnea with severe obesity have increased arterial stiffness that may potentially influence cardiovascular risk independently of metabolic abnormalities. The presence of obstructive sleep apnea in severe obesity identifies a group at high cardiovascular risk; clinicians should ensure that risk factors are managed appropriately in this group whether or not treatment of obstructive sleep apnea is offered or accepted by patients.

Effect of uremic serum and uremic toxins on drug metabolism in human microsomes.

There is increasing evidence that renal impairment modifies nonrenal drug clearance through drug metabolizing cytochrome P450 (CYP) enzymes. In this study, the direct inhibitory effect of serum from chronic renal failure (CRF) patients receiving dialysis was evaluated in CYP3A4 (testosterone) and CYP2B6 (bupropion) metabolism assays. Human liver microsomes were incubated with ultrafiltered serum collected pre- and post-hemodialysis from ten CRF patients. Additionally, several uremic toxins were evaluated in the CYP3A4 assay. In only three patients was there a significant decrease or increase in testosterone or bupropion metabolism post-dialysis. Urea, mannitol, guanidine, homocysteine, uridine and creatinine had no effect on CYP3A4 metabolism. CMPF, hippuric acid and p-cresol had IC50 values that fell within CRF patient plasma concentrations. The IC50 values for indoxyl sulfate and indole-3-acetic acid were greater than CRF plasma concentrations. The lack of a consistent effect on CYP3A4 or CYP2B6 metabolism by uremic serum may be due in part to the frequency of hemodialysis in these patients which reduced the accumulation of uremic toxins. CMPF, hippuric acid and p-cresol have the ability to inhibit CYP3A4 metabolism at clinical concentrations which may correspond to reports of changes in hepatic metabolism in some CRF patients.

Phase I study of the synthetic triterpenoid, 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO), in advanced solid tumors.

BACKGROUND: The triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic Acid (CDDO, previously RTA 401) is a multifunctional molecule that controls cellular growth and differentiation. While CDDO is capable of activating the transcription factor peroxisome proliferator activator receptor-γ (PPARγ), its apoptotic effects in malignant cells have been shown to occur independently of PPARγ. A phase I dose-escalation study was conducted to determine the toxicity, the maximum tolerated dose, and the pharmacokinetics and pharmacodynamics of CDDO, administered as a 5-day continuous infusion every 28 days in patients with advanced cancers. METHODS: An accelerated titration design was followed, with one patient per cohort entered, and doses ranging from 0.6 to 38.4 mg/m(2)/h. Pharmacokinetics of CDDO was assessed and cleaved poly (ADP-ribose) polymerase (c-PARP), as a marker of apoptosis, was measured in peripheral blood mononuclear cells to assess drug effect. RESULTS: Seven patients, one patient per dose level up to dose level 7 (38.4 mg/m(2)/h), were enrolled and received a total of 11 courses of treatment. Cmax increased proportionally with dose. Preclinically determined efficacious blood level (1 µM) of drug was attained at the highest dose level. One patient, at dose level 6, experienced grade 2 mucositis, nausea, vomiting, and anorexia. Four patients developed thromboembolic events subsequently considered as dose-limiting toxicity. No antitumor activity was noted. CONCLUSION: A causal relationship of observed thromboembolic events to CDDO was considered possible but could not be established.

Uniform assessment and ranking of opioid µ receptor binding constants for selected opioid drugs.

The safe disposal of unused opioid drugs is an area of regulatory concern. While toilet flushing is recommended for some drugs to prevent accidental exposure, there is a need for data that can support a more consistent disposal policy based on an assessment of relative risk. For drugs acting at the Mu-opioid receptor (MOR), published measurements of binding affinity (K(i)) are incomplete and inconsistent due to differences in methodology and assay system, leading to a wide range of values for the same drug thus precluding a simple and meaningful relative ranking of drug potency. Experiments were conducted to obtain K(i)'s for 19 approved opioid drugs using a single binding assay in a cell membrane preparation expressing recombinant human MOR. The K(i) values obtained ranged from 0.1380 nM (sufentanil) to 12.486 µM (tramadol). The drugs were separated into three categories based upon their K(i) values: K(i) > 100 nM (tramadol, codeine, meperidine, propoxyphene and pentazocine), K(i)=1-100 nM (hydrocodone, oxycodone, diphenoxylate, alfentanil, methadone, nalbuphine, fentanyl and morphine) and K(i) < 1 nM (butorphanol, levorphanol, oxymorphone, hydromorphone, buprenorphine and sufentanil). These data add to the understanding of the pharmacology of opioid drugs and support the development of a more consistent labeling policies regarding safe disposal.

Plasma and CNS pharmacokinetics of O4-benzylfolic acid (O4BF) and metabolite in a non-human primate model.

PURPOSE: O(6)-alkylguanine-DNA alkyltransferase (AGT) repairs DNA damage from alkylating agents by transferring the alkyl adducts from the O(6)-position of guanine in DNA to AGT. The folate analog O(4)-benzylfolic acid (O(4)BF) is an inhibitor of AGT with reported selectivity of the alpha-folate receptor in tumors. We studied plasma and cerebrospinal fluid (CSF) pharmacokinetics and CSF penetration of O(4)BF in a non-human primate model. METHODS: Rhesus monkeys (Macaca mulatta) received O(4)BF (10-50 mg/kg) intravenously, and serial blood and CSF samples were obtained. Analyte concentrations in plasma were measured by HPLC/photo diode array, and an HPLC/MS/MS assay was used for CSF samples. RESULTS: A putative metabolite of O(4)BF was detected in plasma and CSF. O(4)BF and the metabolite inactivated purified AGT with ED(50) of 0.04 mcM. The median clearance of O(4)BF was 8 ml/min/kg and half-life was 1.1 h. The metabolite had a substantially longer half-life (>20 h) and greater AUC than O(4)BF. The AUC of the metabolite increased disproportionately to the dose of O(4)BF, suggesting saturable elimination. CSF penetration of O(4)BF and its metabolite was < 1%. At the 50 mg/kg dose level, the C(max) in CSF for O(4)BF was less than 0.09 mcM and for the metabolite the C(max) ranged from 0.02 to 0.04 mcM (O(4)BF equivalents). CONCLUSIONS: Concentrations of O(4)BF and the metabolite in CSF exceeded the ED(50) of AGT; however, recently reported lack of receptor specificity and pharmacokinetic data suggesting saturable elimination of both O(4)BF and its metabolite may limit dose-escalation and future clinical development of this agent.

Outcomes of length-stable fixation of femoral neck fractures.

INTRODUCTION: The most common implants for treating unstable femoral neck fractures are sliding constructs, which allow postoperative collapse. Successful healing, typically, is a malunion with a shortened femoral neck. Functional sequelae resulting from altered femoral neck biomechanics have been increasingly reported. Re-operation rate due to nonunion, avascular necrosis, hardware cut-out and prominence is high with this treatment modality. We evaluated the outcomes of patients with femoral neck fractures treated with stable calcar pivot reduction, intraoperative compression across the fracture, and stabilization with length-stable implants. MATERIALS AND METHODS: Fifty-four patients with femoral neck fractures underwent open reduction and internal fixation. Average follow up duration was 23.6 months (range: 15-36 months). There were 23 Garden I, 2 Garden II, 14 Garden III and 15 Garden IV fractures. Reduction was achieved through a modified Smith-Petersen approach. Fractures were compressed initially, and subsequently stabilized with a length-stable device. Post-operative radiographs were assessed for change in fracture alignment. Variation in the femoral neck offset and abductor lever arm measurements was performed using the contralateral hip as control. Functional outcome was assessed using SF-36, Harris Hip Score (HHS) and a gait analysis device. The average patient age was 78 years. Fifty-one (94%) healed without complications. Surgical fixation failed in two patients and one patient developed avascular necrosis. The average femoral neck shortening was 1.7 mm. RESULTS: The average difference in femoral neck offset and the abductor lever arm measurement at the latest follow up was 3.5 and 1.5 mm respectively. The average score on physical, mental components of SF-36 and HHS was 42 and 47 and 87 respectively. By 6 months, patients on average recovered 94% of the single limb stance time, 98% of cadence, 90% of cycle duration, 96% in stride length compared to the uninjured side. CONCLUSION: Reduction with a stable calcar pivot, intraoperative compression and length-stable fixation can achieve high union rates with minimal femoral neck shortening and improved functional outcomes. LEVEL OF EVIDENCE: IV, retrospective with historical controls.

A detailed investigation of the aza-Prins reaction.

The development of a Lewis acid-promoted aza-Prins reaction to form piperidines and pyrrolidines is described. Indium trichloride has been found to be a highly successful and mild Lewis acid for promoting this reaction. A thorough mechanistic investigation is described, including the factors that influence the formation of the 5- or 6-membered ring product(s).