A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

Successful kinetic impact into an asteroid for planetary defence.

Although no known asteroid poses a threat to Earth for at least the next century, the catalogue of near-Earth asteroids is incomplete for objects whose impacts would produce regional devastation1,2. Several approaches have been proposed to potentially prevent an asteroid impact with Earth by deflecting or disrupting an asteroid1-3. A test of kinetic impact technology was identified as the highest-priority space mission related to asteroid mitigation1. NASA's Double Asteroid Redirection Test (DART) mission is a full-scale test of kinetic impact technology. The mission's target asteroid was Dimorphos, the secondary member of the S-type binary near-Earth asteroid (65803) Didymos. This binary asteroid system was chosen to enable ground-based telescopes to quantify the asteroid deflection caused by the impact of the DART spacecraft4. Although past missions have utilized impactors to investigate the properties of small bodies5,6, those earlier missions were not intended to deflect their targets and did not achieve measurable deflections. Here we report the DART spacecraft's autonomous kinetic impact into Dimorphos and reconstruct the impact event, including the timeline leading to impact, the location and nature of the DART impact site, and the size and shape of Dimorphos. The successful impact of the DART spacecraft with Dimorphos and the resulting change in the orbit of Dimorphos7 demonstrates that kinetic impactor technology is a viable technique to potentially defend Earth if necessary.

Momentum transfer from the DART mission kinetic impact on asteroid Dimorphos.

The NASA Double Asteroid Redirection Test (DART) mission performed a kinetic impact on asteroid Dimorphos, the satellite of the binary asteroid (65803) Didymos, at 23:14 UTC on 26 September 2022 as a planetary defence test1. DART was the first hypervelocity impact experiment on an asteroid at size and velocity scales relevant to planetary defence, intended to validate kinetic impact as a means of asteroid deflection. Here we report a determination of the momentum transferred to an asteroid by kinetic impact. On the basis of the change in the binary orbit period2, we find an instantaneous reduction in Dimorphos's along-track orbital velocity component of 2.70 ± 0.10 mm s-1, indicating enhanced momentum transfer due to recoil from ejecta streams produced by the impact3,4. For a Dimorphos bulk density range of 1,500 to 3,300 kg m-3, we find that the expected value of the momentum enhancement factor, ß, ranges between 2.2 and 4.9, depending on the mass of Dimorphos. If Dimorphos and Didymos are assumed to have equal densities of 2,400 kg m-3, [Formula: see text]. These ß values indicate that substantially more momentum was transferred to Dimorphos from the escaping impact ejecta than was incident with DART. Therefore, the DART kinetic impact was highly effective in deflecting the asteroid Dimorphos.

Public health assessment of Kenyan ASGM communities using multi-element biomonitoring, dietary and environmental evaluation.

The Kakamega gold belt's natural geological enrichment and artisanal and small-scale gold mining (ASGM) have resulted in food and environmental pollution, human exposure, and subsequent risks to health. This study aimed to characterise exposure pathways and risks among ASGM communities. Human hair, nails, urine, water, and staple food crops were collected and analysed from 144 ASGM miners and 25 people from the ASGM associated communities. Exposure to PHEs was predominantly via drinking water from mine shafts, springs and shallow-wells (for As>Pb>Cr>Al), with up to 366 µg L-1 arsenic measured in shaft waters consumed by miners. Additional exposure was via consumption of locally grown crops (for As>Ni>Pb>Cr>Cd>Hg>Al) besides inhalation of Hg vapour and dust, and direct dermal contact with Hg. Urinary elemental concentrations for both ASGM workers and wider ASGM communities were in nearly all cases above bioequivalents and reference upper thresholds for As, Cr, Hg, Ni, Pb and Sb, with median concentrations of 12.3, 0.4, 1.6, 5.1, 0.7 and 0.15 µg L-1, respectively. Urinary As concentrations showed a strong positive correlation (0.958) with As in drinking water. This study highlighted the importance of a multidisciplinary approach in integrating environmental, dietary, and public health investigations to better characterise the hazards and risks associated with ASGM and better understand the trade-offs associated with ASGM activities relating to public health and environmental sustainability. Further research is crucial, and study results have been shared with Public Health and Environmental authorities to inform mitigation efforts.

Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia.

BACKGROUND: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin-kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS: A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was -44.5% in the evolocumab group and -6.2% in the placebo group, for a difference of -38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was -77.5 mg per deciliter (-2.0 mmol per liter) in the evolocumab group and -9.0 mg per deciliter (-0.2 mmol per liter) in the placebo group, for a difference of -68.6 mg per deciliter (-1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.).

Ultraconserved elements-based phylogenomic systematics of the snake superfamily Elapoidea, with the description of a new Afro-Asian family.

The highly diverse snake superfamily Elapoidea is considered to be a classic example of ancient, rapid radiation. Such radiations are challenging to fully resolve phylogenetically, with the highly diverse Elapoidea a case in point. Previous attempts at inferring a phylogeny of elapoids produced highly incongruent estimates of their evolutionary relationships, often with very low statistical support. We sought to resolve this situation by sequencing over 4,500 ultraconserved element loci from multiple representatives of every elapoid family/subfamily level taxon and inferring their phylogenetic relationships with multiple methods. Concatenation and multispecies coalescent based species trees yielded largely congruent and well-supported topologies. Hypotheses of a hard polytomy were not retained for any deep branches. Our phylogenies recovered Cyclocoridae and Elapidae as diverging early within Elapoidea. The Afro-Malagasy radiation of elapoid snakes, classified as multiple subfamilies of an inclusive Lamprophiidae by some earlier authors, was found to be monophyletic in all analyses. The genus Micrelaps was consistently recovered as sister to Lamprophiidae. We establish a new family, Micrelapidae fam. nov., for Micrelaps and assign Brachyophis to this family based on cranial osteological synapomorphy. We estimate that Elapoidea originated in the early Eocene and rapidly diversified into all the major lineages during this epoch. Ecological opportunities presented by the post-Cretaceous-Paleogene mass extinction event may have promoted the explosive radiation of elapoid snakes.

Effects of 17α-ethinylestradiol on the neuroendocrine gonadotropic system and behavior of European sea bass larvae (Dicentrarchus labrax).

The widespread use of 17α-ethinylestradiol (EE2), and other estrogenic endocrine disruptors, results in a continuous release of estrogenic compounds into aquatic environments. Xenoestrogens may interfere with the neuroendocrine system of aquatic organisms and may produce various adverse effects. The aim of the present study was to expose European sea bass larvae (Dicentrarchus labrax) to EE2 (0.5 and 50 nM) for 8 d and determine the expression levels of brain aromatase (cyp19a1b), gonadotropin-releasing hormones (gnrh1, gnrh2, gnrh3), kisspeptins (kiss1, kiss2) and estrogen receptors (esr1, esr2a, esr2b, gpera, gperb). Growth and behavior of larvae as evidenced by locomotor activity and anxiety-like behaviors were measured 8 d after EE2 treatment and a depuration period of 20 d. Exposure to 0.5 nM EE2 induced a significant increase in cyp19a1b expression levels, while upregulation of gnrh2, kiss1, and cyp19a1b expression was noted after 8 d at 50 nM EE2. Standard length at the end of the exposure phase was significantly lower in larvae exposed to 50 nM EE2 than in control; however, this effect was no longer observed after the depuration phase. The upregulation of gnrh2, kiss1, and cyp19a1b expression levels was found in conjunction with elevation in locomotor activity and anxiety-like behaviors in larvae. Behavioral alterations were still detected at the end of the depuration phase. Evidence indicates that the long-lasting effects of EE2 on behavior might impact normal development and subsequent fitness of exposed fish.

High-resolution shape models of Phobos and Deimos from stereophotoclinometry.

We created high-resolution shape models of Phobos and Deimos using stereophotoclinometry and united images from Viking Orbiter, Phobos 2, Mars Global Surveyor, Mars Express, and Mars Reconnaissance Orbiter into a single coregistered collection. The best-fit ellipsoid to the Phobos model has radii of (12.95 ± 0.04) km × (11.30 ± 0.04) km × (9.16 ± 0.03) km, with an average radius of (11.08 ± 0.04) km. The best-fit ellipsoid to the Deimos model has radii of (8.04 ± 0.08) km × (5.89 ± 0.06) km × (5.11 ± 0.05) km with an average radius of (6.27 ± 0.07) km. The new shape models offer substantial improvements in resolution over existing shape models, while remaining globally consistent with them. The Phobos model resolves grooves, craters, and other surface features ~ 100 m in size across the entire surface. The Deimos model is the first to resolve geological surface features. These models, associated data products, and a searchable, coregistered collection of images across six spacecraft are publicly available in the Small Body Mapping Tool, and will be archived with the NASA Planetary Data System. These products enable an array of future studies to advance the understanding of Phobos and Deimos, facilitate coregistration of other past and future datasets, and set the stage for planning and operating future missions to the moons, including the upcoming Martian Moons eXploration (MMX) mission. Supplementary Information: The online version contains supplementary material available at 10.1186/s40623-023-01814-7.

Online Microdialysis-High-Performance Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry (MD-HPLC-ICP-MS) as a Novel Tool for Sampling Hexavalent Chromium in Soil Solution.

Conventional soil solution sampling of species-sensitive inorganic contaminants, such as hexavalent chromium (CrVI), may induce interconversions due to disruption of system equilibrium. The temporal resolution that these sampling methods afford may also be insufficient to capture dynamic interactions or require time-consuming and expensive analysis. Microdialysis (MD) is emerging as a minimally invasive passive sampling method in environmental science, permitting the determination of solute fluxes and concentrations at previously unobtainable spatial scales and time frames. This article presents the first use of MD coupled to high-performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) for the continuous sampling and simultaneous detection of CrVI in soil solution. The performance criteria of the system were assessed using stirred solutions; good repeatability of measurement (RSD < 2.5%) was obtained for CrVI, with a detection limit of 0.2 µg L-1. The online MD-HPLC-ICP-MS setup was applied to the sampling of native CrVI in three soils with differing geochemical properties. The system sampled and analyzed fresh soil solution at 15 min intervals, offering improved temporal resolution and a significant reduction in analysis time over offline MD. Simple modifications to the chromatographic conditions could resolve additional analytes, offering a powerful tool for the study of solute fluxes in soil systems to inform research into nutrient availability or soil-to-plant transfer of potentially harmful elements.

Belgian data of ODYSSEY APPRISE: stringent LDL-c targets are in reach when using all available tools.

BACKGROUND: As lipid targets became more stringent in the latest ESC/EAS guidelines, many patients on statin monotherapy are left above their risk-based target, increasing the need for lipid-lowering therapies. The results of the ODYSSEY APPRISE study were recently published by Gaudet et al In this trial, alirocumab (a PCSK9 inhibitor) was investigated in high cardiovascular risk patients in a real-life setting. OBJECTIVE: We aim at analysing the characteristics, safety and efficacy of alirocumab in the Belgian population of the ODYSSEY APPRISE trial and, based on literature research, we aim to evaluate the importance and the need for the add-on, non-statin lipid-lowering therapy in clinical practice. METHODS AND RESULTS: ODYSSEY APPRISE is a multicentric, prospective, single-arm, Phase 3b open-label trial. A total of 68 Belgian patients were enrolled, 63 patients had heterozygous familial hypercholesterolaemia (HeFH). Baseline mean LDL-c was 188.7 mg/dL (SD ± 51.8). At week 12, 65 patients had an evaluable efficacy end point with a mean LDL-c reduction of 59.9% from baseline. The overall incidence of treatment-emergent adverse events (TEAEs) was 75.0%. The most frequent TEAE was back pain (10.3%), nasopharyngitis (10.3%) and injection site erythema (8.8%). Based on the literature, a majority of patients do not reach their risk-based lipid target despite statin therapy alone. CONCLUSION: In a real-life setting, alirocumab is both well-tolerated, safe and very effective in reducing LDL-c in this Belgian cohort. In clinical practice, more patients should be initiated on the add-on, non-statin lipid-lowering therapy in order to reach their risk-based lipid target.

Faecal and nitrate contamination in the groundwater of Mardan district, Pakistan.

This study aimed to determine the status of groundwater contamination with faecal coliform and nitrate in the rural areas of Mardan district, Pakistan. Both analytes require regular monitoring according to the National Environmental Quality Standards (NEQS) of Pakistan. Groundwater samples (n = 100) were collected from 25 villages across four zones. Samples were analysed for physicochemical parameters including pH, electrical conductivity (EC), Escherichia coli (E. coli) contamination, nitrite, and nitrate ([Formula: see text] and [Formula: see text]). Whilst the average concentrations of [Formula: see text] in the water samples were within the permissible limits of 50 mg L-1 set by the World Health Organisation (WHO) and NEQS two villages exceeded the safety limits. Non-carcinogenic health risks of [Formula: see text] were estimated in terms of average daily dose (ADD) and hazard quotient (HQ). The HQ values for [Formula: see text] were > 1 for children signifying potential health risks; however, the adult population had HQ < 1 which indicates no risk. Groundwater samples tested positive for E. coli contamination in 13 villages, suggesting that residents may be living at risk of various microbial diseases due to drinking of contaminated water. The findings of this study provide valuable baseline data for groundwater researchers, policymakers, and the local public health department.

Short-Term Iodine Dynamics in Soil Solution.

Assessing the reactions of iodine (I) in soil is critical to evaluate radioiodine exposure and understand soil-to-crop transfer rates. Our mechanistic understanding has been constrained by method limitations in assessing the dynamic interactions of iodine between soil solution and soil solid phase over short periods (hours). We use microdialysis to passively extract soil solution spiked with radioiodine (129I- and 129IO3-) to monitor short-term (≤40 h) in situ fixation and speciation changes. We observed greater instantaneous adsorption of 129IO3- compared to 129I- in all soils and the complete reduction of 129IO3- to 129I- within 5 h of addition. Loss of 129I from solution was extremely rapid; the average half-lives of 129I- and 129IO3- in soil solution were 4.06 and 10.03 h, respectively. We detected the presence of soluble organically bound iodine (org-129I) with a low molecular weight (MW) range (0.5-5 kDa) in all soils and a slower (20-40 h) time-dependent formation of larger MW org-I compounds (12-18 kDa) in some samples. This study highlights the very short window of immediate availability in which I from rainfall or irrigation remains in soil solution and available to crops, thus presenting significant challenges to phytofortification strategies in soil-based production systems.

Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM.

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total - HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.

Iodine status in western Kenya: a community-based cross-sectional survey of urinary and drinking water iodine concentrations.

Spot urinary iodine concentrations (UIC) are presented for 248 individuals from western Kenya with paired drinking water collected between 2016 and 2018. The median UIC was 271 µg L-1, ranging from 9 to 3146 µg L-1, unadjusted for hydration status/dilution. From these data, 12% were potentially iodine deficient (< 100 µg L-1), whilst 44% were considered to have an excess iodine intake (> 300 µg L-1). The application of hydration status/urinary dilution correction methods was evaluated for UICs, using creatinine, osmolality and specific gravity. The use of specific gravity correction for spot urine samples to account for hydration status/urinary dilution presents a practical approach for studies with limited budgets, rather than relying on unadjusted UICs, 24 h sampling, use of significantly large sample size in a cross-sectional study and other reported measures to smooth out the urinary dilution effect. Urinary corrections did influence boundary assessment for deficiency-sufficiency-excess for this group of participants, ranging from 31 to 44% having excess iodine intake, albeit for a study of this size. However, comparison of the correction methods did highlight that 22% of the variation in UICs was due to urinary dilution, highlighting the need for such correction, although creatinine performed poorly, yet specific gravity as a low-cost method was comparable to osmolality corrections as the often stated 'gold standard' metric for urinary concentration. Paired drinking water samples contained a median iodine concentration of 3.2 µg L-1 (0.2-304.1 µg L-1). A weak correlation was observed between UIC and water-I concentrations (R = 0.11).

A systematic review and network meta-analysis of different surgical approaches for pancreaticoduodenectomy.

BACKGROUND: Minimally invasive pancreaticoduodenectomy (MIPD) is a demanding surgical procedure, thus explaining its slow expansion and limited popularity amongst Hepato-Pancreatico-Biliary (HPB) surgeons. However, three main advantages of robotic assisted pancreaticoduodenectomy (PD) including improved dexterity, 3D vision less surgical fatigue, may overcome some of the hurdles and ultimately lead to a wider adoption. This systematic review and network meta-analysis aims to evaluate the current literature on open and MIPD. METHODS: A systematic literature search was conducted for studies reporting robotic, laparoscopic and open surgery for PD. Network meta-analysis of intraoperative (operating time, blood loss, transfusion rate), postoperative (overall and major complications, pancreatic fistula, delayed gastric emptying, length of hospital stay) and oncological outcomes (R0 resection, lymphadenectomy) were performed. RESULTS: Sixty-one studies including 62,529 patients were included in the network meta-analysis, of which 3% (n = 2131) were totally robotic (TR) and 10% (n = 6514) were totally laparoscopic (TL). There were no significant differences between surgical techniques for major complications, overall and grade B/C fistula, biliary leak, mortality and R0 resections. Transfusion rates were significantly lower in TR compared to TL and open. Operative time for TR was longer compared with open and TL. Both TL and TR were associated with significantly lower rates of wound infections, pulmonary complications, shorter length of stay and higher lymph nodes examined when compared to open. TR was associated with significantly lower conversion rates than TL. CONCLUSION: In summary, this network meta-analysis highlights the variability in techniques within MIPD and compares other variations to the conventional open PD. Current evidence appears to demonstrate MIPD, both laparoscopic and robotic techniques are associated with improved rates of surgical site infections, pulmonary complications, and a shorter hospital stay, with no compromise in oncological outcomes for cancer resections.

Quantifying Atherogenic Lipoproteins: Current and Future Challenges in the Era of Personalized Medicine and Very Low Concentrations of LDL Cholesterol. A Consensus Statement from EAS and EFLM.

BACKGROUND: The European Atherosclerosis Society-European Federation of Clinical Chemistry and Laboratory Medicine Consensus Panel aims to provide recommendations to optimize atherogenic lipoprotein quantification for cardiovascular risk management. CONTENT: We critically examined LDL cholesterol, non-HDL cholesterol, apolipoprotein B (apoB), and LDL particle number assays based on key criteria for medical application of biomarkers. (a) Analytical performance: Discordant LDL cholesterol quantification occurs when LDL cholesterol is measured or calculated with different assays, especially in patients with hypertriglyceridemia >175 mg/dL (2 mmol/L) and low LDL cholesterol concentrations <70 mg/dL (1.8 mmol/L). Increased lipoprotein(a) should be excluded in patients not achieving LDL cholesterol goals with treatment. Non-HDL cholesterol includes the atherogenic risk component of remnant cholesterol and can be calculated in a standard nonfasting lipid panel without additional expense. ApoB more accurately reflects LDL particle number. (b) Clinical performance: LDL cholesterol, non-HDL cholesterol, and apoB are comparable predictors of cardiovascular events in prospective population studies and clinical trials; however, discordance analysis of the markers improves risk prediction by adding remnant cholesterol (included in non-HDL cholesterol) and LDL particle number (with apoB) risk components to LDL cholesterol testing. (c) Clinical and cost-effectiveness: There is no consistent evidence yet that non-HDL cholesterol-, apoB-, or LDL particle-targeted treatment reduces the number of cardiovascular events and healthcare-related costs than treatment targeted to LDL cholesterol. SUMMARY: Follow-up of pre- and on-treatment (measured or calculated) LDL cholesterol concentration in a patient should ideally be performed with the same documented test method. Non-HDL cholesterol (or apoB) should be the secondary treatment target in patients with mild to moderate hypertriglyceridemia, in whom LDL cholesterol measurement or calculation is less accurate and often less predictive of cardiovascular risk. Laboratories should report non-HDL cholesterol in all standard lipid panels.

Phylogeny and biogeography of the African burrowing snake subfamily Aparallactinae (Squamata: Lamprophiidae).

Members of the snake subfamily Aparallactinae occur in various habitats throughout sub-Saharan Africa. The monophyly of aparallactine snakes is well established, but relationships within the subfamily are poorly known. We sampled 158 individuals from six of eight aparallactine genera in sub-Saharan Africa. We employed concatenated gene-tree analyses, divergence dating approaches, and ancestral-area reconstructions to infer phylogenies and biogeographic patterns with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1). As a result, we uncover several cryptic lineages and elevate a lineage of Polemon to full species status. Diversification occurred predominantly during the Miocene, with a few speciation events occurring subsequently in the Pliocene and Pleistocene. Biogeographic analyses suggested that the Zambezian biogeographic region, comprising grasslands and woodlands, facilitated radiations, vicariance, and dispersal for many aparallactines. Moreover, the geographic distributions of many forest species were fragmented during xeric and cooler conditions, which likely led to diversification events. Biogeographic patterns of aparallactine snakes are consistent with previous studies of other sub-Saharan herpetofauna.

Anti-PCSK9 antibodies for hypercholesterolaemia: Overview of clinical data and implications for primary care.

OBJECTIVES: To put data from our recent systematic review of phase 3 studies of anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies into the context of clinical practice. METHODS: Data from studies previously identified by a systematic review of phase 3 studies of alirocumab and evolocumab and additional references from non-systematic literature searches were used. We evaluated the hypothetical cardiovascular (CV) benefit in cases of typical patients in whom anti-PCSK9 antibodies may be recommended, using preliminary major CV event (CVE) rates from long-term clinical trials of anti-PCSK9 antibodies and from extrapolations derived from correlation between low-density lipoprotein cholesterol (LDL-C) reduction and CV benefit with other lipid-lowering therapies (LLTs). RESULTS: Rapid (within 1-2 weeks) and persistent (8-74 weeks) reductions in LDL-C levels were achieved with anti-PCSK9 antibodies. When combined with statins (± ezetimibe), high rates of LDL-C goal achievement were observed (41%-87% with alirocumab and 63%-100% with evolocumab). In long-term alirocumab and evolocumab studies, reductions in major CVEs of 48% and 53%, respectively, were observed. For every 38.7 mg/dL (1 mmol/L) reduction in LDL-C, a 22% reduction in relative CVE risk is predicted. Applying these assumptions to typical patients who have high-very high risk (15%-60% absolute 10-year CVE risk) and elevated LDL-C despite maximally tolerated statins, the 10-year number needed to treat with an anti-PCSK9 antibody to prevent one additional CVE varies from 4 to 26, depending on baseline LDL-C levels and residual absolute CVE risk. CONCLUSIONS: Anti-PCSK9 antibodies effectively lower LDL-C levels in a broad patient population. While awaiting comprehensive data from CV outcome trials, these agents should be considered in very high risk patients, such as those in secondary prevention and those with familial hypercholesterolaemia who are already receiving maximally tolerated LLTs, have not achieved their LDL-C goal and require substantial reductions in LDL-C.

Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine.

AIMS: To critically evaluate the clinical implications of the use of non-fasting rather than fasting lipid profiles and to provide guidance for the laboratory reporting of abnormal non-fasting or fasting lipid profiles. METHODS AND RESULTS: Extensive observational data, in which random non-fasting lipid profiles have been compared with those determined under fasting conditions, indicate that the maximal mean changes at 1-6 h after habitual meals are not clinically significant [+0.3 mmol/L (26 mg/dL) for triglycerides; -0.2 mmol/L (8 mg/dL) for total cholesterol; -0.2 mmol/L (8 mg/dL) for LDL cholesterol; +0.2 mmol/L (8 mg/dL) for calculated remnant cholesterol; -0.2 mmol/L (8 mg/dL) for calculated non-HDL cholesterol]; concentrations of HDL cholesterol, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) are not affected by fasting/non-fasting status. In addition, non-fasting and fasting concentrations vary similarly over time and are comparable in the prediction of cardiovascular disease. To improve patient compliance with lipid testing, we therefore recommend the routine use of non-fasting lipid profiles, while fasting sampling may be considered when non-fasting triglycerides >5 mmol/L (440 mg/dL). For non-fasting samples, laboratory reports should flag abnormal concentrations as triglycerides ≥2 mmol/L (175 mg/dL), total cholesterol ≥5 mmol/L (190 mg/dL), LDL cholesterol ≥3 mmol/L (115 mg/dL), calculated remnant cholesterol ≥0.9 mmol/L (35 mg/dL), calculated non-HDL cholesterol ≥3.9 mmol/L (150 mg/dL), HDL cholesterol ≤1 mmol/L (40 mg/dL), apolipoprotein A1 ≤1.25 g/L (125 mg/dL), apolipoprotein B ≥1.0 g/L (100 mg/dL), and lipoprotein(a) ≥50 mg/dL (80th percentile); for fasting samples, abnormal concentrations correspond to triglycerides ≥1.7 mmol/L (150 mg/dL). Life-threatening concentrations require separate referral when triglycerides >10 mmol/L (880 mg/dL) for the risk of pancreatitis, LDL cholesterol >13 mmol/L (500 mg/dL) for homozygous familial hypercholesterolaemia, LDL cholesterol >5 mmol/L (190 mg/dL) for heterozygous familial hypercholesterolaemia, and lipoprotein(a) >150 mg/dL (99th percentile) for very high cardiovascular risk. CONCLUSION: We recommend that non-fasting blood samples be routinely used for the assessment of plasma lipid profiles. Laboratory reports should flag abnormal values on the basis of desirable concentration cut-points. Non-fasting and fasting measurements should be complementary but not mutually exclusive.

Fasting Is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cutpoints-A Joint Consensus Statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine.

AIMS: To critically evaluate the clinical implications of the use of non-fasting rather than fasting lipid profiles and to provide guidance for the laboratory reporting of abnormal non-fasting or fasting lipid profiles. METHODS AND RESULTS: Extensive observational data, in which random non-fasting lipid profiles have been compared with those determined under fasting conditions, indicate that the maximal mean changes at 1-6 h after habitual meals are not clinically significant [+0.3 mmol/L (26 mg/dL) for triglycerides; -0.2 mmol/L (8 mg/dL) for total cholesterol; -0.2 mmol/L (8 mg/dL) for LDL cholesterol; +0.2 mmol/L (8 mg/dL) for calculated remnant cholesterol; -0.2 mmol/L (8 mg/dL) for calculated non-HDL cholesterol]; concentrations of HDL cholesterol, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) are not affected by fasting/non-fasting status. In addition, non-fasting and fasting concentrations vary similarly over time and are comparable in the prediction of cardiovascular disease. To improve patient compliance with lipid testing, we therefore recommend the routine use of non-fasting lipid profiles, whereas fasting sampling may be considered when non-fasting triglycerides are >5 mmol/L (440 mg/dL). For non-fasting samples, laboratory reports should flag abnormal concentrations as triglycerides ≥2 mmol/L (175 mg/dL), total cholesterol ≥5 mmol/L (190 mg/dL), LDL cholesterol ≥3 mmol/L (115 mg/dL), calculated remnant cholesterol ≥0.9 mmol/L (35 mg/dL), calculated non-HDL cholesterol ≥3.9 mmol/L (150 mg/dL), HDL cholesterol ≤1 mmol/L (40 mg/dL), apolipoprotein A1 ≤1.25 g/L (125 mg/dL), apolipoprotein B ≥1.0 g/L (100 mg/dL), and lipoprotein(a) ≥50 mg/dL (80th percentile); for fasting samples, abnormal concentrations correspond to triglycerides ≥1.7 mmol/L (150 mg/dL). Life-threatening concentrations require separate referral for the risk of pancreatitis when triglycerides are >10 mmol/L (880 mg/dL), for homozygous familial hypercholesterolemia when LDL cholesterol is >13 mmol/L (500 mg/dL), for heterozygous familial hypercholesterolemia when LDL cholesterol is >5 mmol/L (190 mg/dL), and for very high cardiovascular risk when lipoprotein(a) >150 mg/dL (99th percentile). CONCLUSIONS: We recommend that non-fasting blood samples be routinely used for the assessment of plasma lipid profiles. Laboratory reports should flag abnormal values on the basis of desirable concentration cutpoints. Non-fasting and fasting measurements should be complementary but not mutually exclusive.