Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?

The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat < 30 cm H2O), positive end expiratory pressure (PEEP > 5 cm H2O) and tidal volume (Vt of 6 ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.

A multidimensional approach for microplastics monitoring in two major tropical river basins, Malaysia.

Microplastics (MPs) with the size of 1 µm-5 mm are pollutants of great concern ubiquitously found in the environment. Existing efforts have found that most of the MPs present in the seas mainly originated from land via riverine inputs. Asian rivers are known to be among the top in microplastic emissions. However, field data are scarce, especially in Malaysia. This study presents the distribution and characteristics of MPs in the surface water of two major river basins of Malaysia, namely Langat River (West Coast/Straits of Malacca) and Kelantan River (East Coast/South China Sea). Water samples were collected at 21-22 locations in Kelantan and Langat rivers, covering the river, estuary and sea. MPs were physically classified based on sizes, shapes, colours and surface morphology (SEM-EDS). The average of 179.6 items/L and 1464.8 items/L of MPs had been quantified from Kelantan and Langat rivers, respectively. Fibre (91.90%) was highly recorded at Kelantan, compared to Langat whereby both fibre (59.21%) and fragment (38.87%) were prevalence. Anthropogenic activities and urbanised areas contribute to high microplastic abundance, especially in the Langat River. Micro-FTIR analysis identified 14 polymers in Kelantan River, whereas 20 polymers were found in Langat River. Polypropylene, polyethylene, polyethylene terephthalate, nylon, phenoxy resins, poly(methyl acrylate), poly(methyl methacrylate), polystyrene, polytetrafluoroethylene, polyurethane and rayon were discovered in both rivers, although only polyethylene was significant (>1 ppm) when further analysed using pyrolysis-GC/MS. Correlation analysis and multiple linear regression were used to explain the relationship between water quality and MP abundance, suggesting only turbidity was positively significant to the microplastic occurrence. This comprehensive study is first to suggest a full-scale monitoring protocol for MPs in Malaysian riverine system and is significant in understanding MPs abundance in correlation to in-situ environmental factors. Consequently, this will allow the right authorities to develop mitigation strategies to address riverine plastic pollution in major river basins in Malaysia and the South East Asia.

Nephrocalcinosis in juvenile farmed Atlantic Salmon (Salmo salar) may be linked to osmoregulatory stress.

Nephrocalcinosis is a widespread challenge in intensive production of salmon smolt. There is however no consensus on its aetiology, which makes it problematic to implement proper measures to limit its development. We performed a survey of nephrocalcinosis prevalence and environmental factors in 11 different hatcheries in Mid-Norway as well as a 6-month monitoring in one of the hatcheries. A multivariate analysis indicated that the most influencing factor for the prevalence of nephrocalcinosis was the supplementation of sea water during smolt production. In the 6-month monitoring, the hatchery introduced salinity in the production water prior to the change in day length. Mismatch in those environmental signals may increase the risk for developing nephrocalcinosis. Salinity fluctuations prior to smoltification can cause osmotic stress and result in unbalanced levels of ions in fish blood. This was clearly illustrated in our study, as the fish experienced chronic hypercalcaemia and hypermagnesaemia. Both magnesium and calcium are excreted over the kidneys and it is possible that their prolonged, elevated levels in plasma resulted in an oversaturation of the urine when finally excreted. This again could have led to the aggregation of calcium deposits within the kidney. This study indicates a relationship between osmotic stress induced by salinity changes in juvenile Atlantic salmon and the development of nephrocalcinosis. Other factors that may affect the severity of nephrocalcinosis are currently subjects for discussion.

Microscopic Description of 2α Decay in

A microscopic calculation of half-lives for both the α and 2α decays of ^{212}Po and ^{224}Ra is performed, using a self-consistent framework based on energy density functionals. A relativistic density functional and a separable pairing interaction of finite range are used to compute axially symmetric deformation energy surfaces as functions of quadrupole, octupole, and hexadecapole collective coordinates. Dynamical least-action paths are determined, that trace the α and 2α emission from the equilibrium deformation to the point of scission. The calculated half-lives for the α decay of ^{212}Po and ^{224}Ra are in good agreement with data. A new decay mode, the symmetric 2α emission, is predicted with half-lives of the order of those observed for cluster emission.

Microbiology of diabetic foot infections in three district hospital in Malaysia and comparison with South East Asian Countries.

INTRODUCTION: Diabetic foot infection, a complication that is associated with lower-limb amputation, incurs a huge economic burden to the hospital and health care system of Malaysia. The bacteriological profile of pathogens in diabetic foot infections in Malaysia has been sparsely studied. We investigated the microbiology of diabetic foot infections in patients admitted to the district hospitals on the east coast of Malaysia. METHODS: A retrospective analysis was conducted in three district hospitals (Hospital Kuala Lipis, Hospital Bentong and Hospital Raub) in Malaysia from 1st of January 2016 to 31st December 2016. The clinical specimens were cultured using Clinical and Laboratory Standards Institute (CLSI) guidelines. Antibiotic sensitivity testing to different antibiotics was carried out using the disc diffusion method. RESULT: A total of 188 pathogens were isolated from 173 patients, with an average of 1.09 pathogens per lesion. Majority of the pathogens isolated were gram negative pathogens (73.4%). The most commonly isolated pathogens were Staphylococcus aureus (17.5%). This was followed by Klebsiella spp. (17%), Pseudomonas spp. (15.4%) and Proteus spp. (13.8%). Gram positive pathogens were sensitive to most of the antibiotics tested except penicillin and fusidic acid. Gram negative pathogens were sensitive to all antibiotics tested except ampicillin and amoxicillin/clavulanic acid. Amikacin provide coverage for all gram negative pathogens in DFI. CONCLUSION: For the management of patient with infection in diabetic foot, the choice of antibiotic therapy depends on the sensitivity of the pathogens, the severity of the infection, the patient's allergies history, toxicity and excretion of the antibiotics.

How atomic nuclei cluster.

Nucleonic matter displays a quantum-liquid structure, but in some cases finite nuclei behave like molecules composed of clusters of protons and neutrons. Clustering is a recurrent feature in light nuclei, from beryllium to nickel. Cluster structures are typically observed as excited states close to the corresponding decay threshold; the origin of this phenomenon lies in the effective nuclear interaction, but the detailed mechanism of clustering in nuclei has not yet been fully understood. Here we use the theoretical framework of energy-density functionals, encompassing both cluster and quantum liquid-drop aspects of nuclei, to show that conditions for cluster formation can in part be traced back to the depth of the confining nuclear potential. For the illustrative example of neon-20, we show that the depth of the potential determines the energy spacings between single-nucleon orbitals in deformed nuclei, the localization of the corresponding wavefunctions and, therefore, the degree of nucleonic density clustering. Relativistic functionals, in particular, are characterized by deep single-nucleon potentials. When compared to non-relativistic functionals that yield similar ground-state properties (binding energy, deformation, radii), they predict the occurrence of much more pronounced cluster structures. More generally, clustering is considered as a transitional phenomenon between crystalline and quantum-liquid phases of fermionic systems.

The burden and epidemiology of community-acquired central nervous system infections: a multinational study.

Risk assessment of central nervous system (CNS) infection patients is of key importance in predicting likely pathogens. However, data are lacking on the epidemiology globally. We performed a multicenter study to understand the burden of community-acquired CNS (CA-CNS) infections between 2012 and 2014. A total of 2583 patients with CA-CNS infections were included from 37 referral centers in 20 countries. Of these, 477 (18.5%) patients survived with sequelae and 227 (8.8%) died, and 1879 (72.7%) patients were discharged with complete cure. The most frequent infecting pathogens in this study were Streptococcus pneumoniae (n = 206, 8%) and Mycobacterium tuberculosis (n = 152, 5.9%). Varicella zoster virus and Listeria were other common pathogens in the elderly. Although staphylococci and Listeria resulted in frequent infections in immunocompromised patients, cryptococci were leading pathogens in human immunodeficiency virus (HIV)-positive individuals. Among the patients with any proven etiology, 96 (8.9%) patients presented with clinical features of a chronic CNS disease. Neurosyphilis, neurobrucellosis, neuroborreliosis, and CNS tuberculosis had a predilection to present chronic courses. Listeria monocytogenes, Staphylococcus aureus, M. tuberculosis, and S. pneumoniae were the most fatal forms, while sequelae were significantly higher for herpes simplex virus type 1 (p < 0.05 for all). Tackling the high burden of CNS infections globally can only be achieved with effective pneumococcal immunization and strategies to eliminate tuberculosis, and more must be done to improve diagnostic capacity.

Wheat Growth in Soils Treated by Ex Situ Thermal Desorption.

Successful remediation of oil-contaminated agricultural land may include the goal of returning the land to prespill levels of agricultural productivity. This productivity may be measured by crop yield, quality, and safety, all of which are influenced by soil characteristics. This research was conducted to determine if these metrics are affected in hard red spring wheat ( L. cultivar Barlow) when grown in soils treated by ex situ thermal desorption (TD) compared with wheat grown in native topsoil (TS). Additionally, TD soils were mixed with TS at various ratios to assess the effectiveness of soil mixing as a procedure for enhancing productivity. In two greenhouse studies, TD soils alone produced similar amounts of grain and biomass as TS, although grain protein in TD soils was 22% (±7%) lower. After mixing TS into TD soils, the mean biomass and grain yield were reduced by up to 60%, but grain protein increased. These trends are likely the result of nutrient availability determined by soil organic matter and nutrient cycling performed by soil microorganisms. Thermal desorption soil had 84% (±2%) lower soil organic carbon than TS, and cumulative respiration was greatly reduced (66 ± 2%). From a food safety perspective, grain from TD soils did not show increased uptake of polycyclic aromatic hydrocarbons. Overall, this research suggests that TD soils are capable of producing safe, high-quality grain yields.

Outcome of Pregnancy Related Acute Kidney Injury Observed in a Tertiary Care Hospital.

This prospective case control study was carried out in Mymensingh Medical College Hospital (MMCH) from April 2011 to March 2012. The main objective of the study was to determine the short term maternal outcome of pregnancy related Acute Kidney Injury and to identify aetiological factors and to observe clinical features of pregnancy related Acute Kidney Injury. Total 60 pregnant women with AKI were included in the study as sample and equal (60) number of pregnant women with normal renal function was taken as control. Mean ages (±SD) of study and control group were observed 31.6±6.9 years and 25.5±4.7 years respectively. It was observed that most patients were from rural area with low income group. Most women were multiparous and presented in third trimester and postpartum period. Majority of the study subjects did not receive antenatal care at any stage of pregnancy. Fifty (86.7%) of the study subjects were oligo-anuric, forty-nine (81.7%) were edematous and fifty one (85%) were anaemic. Twenty-five (41.7%) patients presented with abnormal vaginal bleeding. Sepsis (including septic abortion and puerperal sepsis) was responsible for of Pregnancy Related AKI (PR-AKI) in more than two fifths of cases. Haemorrhage (APH & PPH combined) was the next common cause of Pregnancy Related AKI (PR-AKI). Toxemia of Pregnancy was responsible in one fourth of cases. Dialysis (HD & IPD combined) was required for two fifths of the patients. Rest patients were treated conservatively with antibiotics, blood transfusion, maintenance of fluid and electrolytes balance etc. Maternal outcome of Pregnancy related acute kidney injury was considered for the period of patient's hospital staying. 56.6% patients recovered completely, 15.0% patients recovered partially, 6.7% did not recover at the time of hospital discharge; while 21.7% died. So it can be concluded that, pregnancy related acute kidney injury is a critical condition, associated with worse prognosis.

Evaluation of foot and mouth vaccination for yak (Bos grunniens) in Pakistan.

In northern Pakistan, many farming communities rely on domestic yak (Bos grunniens) as a principle source of income. A 2006 participatory disease surveillance report from this region indicated that foot-and-mouth disease (FMD) is the most prevalent annual disease of yak. Our objectives of this study were to determine exposure levels of yak to FMD virus; implement a vaccination program based on current, regional FMD virus serotypes and subtypes; and quantify immune responses following vaccination. Blood samples were used to determine pre-vaccination exposure of animals to FMD virus by antibody presence to non-structural proteins of FMD virus using a 3-ABC trapping indirect ELISA. Vaccine used consisted of FMD serotypes 'O' (PanAsia-2), 'A' (Iran-05), and 'Asia-1' (Shamir), but changed later during the study to match newly circulating viruses in the country ('O'-PanAsia-2; 'A'-Turk-06 and Asia-1-Sindh-08). Three hundred sixty-three blood samples were tested from selected villages to determine pre-vaccination FMD virus exposure in yak with an average of 37.7%. Immune responses from initial vaccination and booster dose 30 days later showed clear protective levels (as mean percent inhibition) of antibodies against structural proteins of serotypes 'O,' 'A,' and 'Asia-1.' These responses remained above threshold positive level even at day 210 following initial vaccination. Results of sero-surveillance and anecdotal information of repeated FMD outbreaks demonstrate the persistence of FMD virus of yak in northern Pakistan. Laboratory results and field observations clearly indicated that yak can be protected against FMD with a good quality vaccine with FMD serotype(s) matching current, regionally circulating FMD virus.

Isolation frequency and susceptibility pattern of non-O1 and non-O139 Vibrio cholerae in a tertiary health care laboratory, 1999-2012.

In the past decade the importance of non-O1 and non-O139 strains of Vibrio cholerae has been highlighted globally. This study aimed to evaluate the frequency and antimicrobial susceptibility profile of non-O1 and non-O139 V. cholerae in Pakistan. Data of stool specimens yielding growth of non-O1 and non-O139 V. cholerae isolated at a national referral laboratory from 1999 to 2012 were retrospectively analysed and evaluated for resistance to ampicillin, tetracycline, chloramphenicol, co-trimoxazole and ofloxacin. A total of 95 800 stool samples submitted over 1999-2012 yielded 3668 strains of V. cholerae, of which 6% were non-O1 and non-O139 V. cholerae. A high isolation rate was found in the summer season, with a peak in the year 2003. Antimicrobial susceptibility data revealed increasing resistance to co-trimoxazole and ampicillin, but strains remained highly susceptible to ofloxacin. Active surveillance of serotypes and antimicrobial susceptibility is essential to predict future epidemics and define measures to curtail the disease.

The exaggerated inflammatory response in Behçet's syndrome: identification of dysfunctional post-transcriptional regulation of the IFN-γ/CXCL10 IP-10 pathway.

The mechanisms underlying the exaggerated inflammatory response in Behçet's syndrome (BS) remain poorly understood. We investigated the response of CD14(+) blood monocytes to interferon (IFN)-γ, focusing on the chemokine CXCL10. Chemokine synthesis and release were analysed at a protein and mRNA level following stimulation with IFN-γ. Findings in BS patients were compared with 25 healthy controls (HC), 15 rheumatoid arthritis (RA) and 15 systemic lupus erythematosus (SLE) disease control patients. BS monocytes produced significantly more CXCL10 protein than HC monocytes from 2 h following IFN-γ stimulation, despite equivalent quantities of mRNA, suggesting more efficient translation. This was significantly more pronounced in BS with high disease activity and in those with ocular and neurological clinical manifestations. The imbalance between CXCL10 protein and mRNA expression was not observed in either RA or SLE patients, and was not seen with other chemokines studied (CXCL9, CXCL11 and CCL2). Furthermore, BS monocytes treated with an alternative stimulant (LPS) did not show abnormal tumour necrosis factor (TNF)-α release. Sucrose density gradients to segregate monocyte CXCL10 mRNA into free RNA or polysome-associated RNA showed equal proportions in BS and HC samples, suggesting that the difference between BS and HC may be due to reduced negative control of CXCL10 translation in BS at a post-initiation level. We conclude that BS monocytes have dysfunctional post-transcriptional regulation of CXCL10 mRNA, resulting in over-expression of CXCL10 protein upon IFN-γ stimulation. As CXCL10 is a chemokine that recruits mononuclear cells, this abnormality may contribute to the exaggerated inflammatory responses that characterizes BS.

Measurement of the isoscalar monopole response in the neutron-rich nucleus 68Ni.

The isoscalar monopole response has been measured in the unstable nucleus (68)Ni using inelastic alpha scattering at 50A MeV in inverse kinematics with the active target MAYA at GANIL. The isoscalar giant monopole resonance (ISGMR) centroid was determined to be 21.1 ± 1.9 MeV and indications for a soft monopole mode are provided for the first time at 12.9 ± 1.0 MeV. Analysis of the corresponding angular distributions using distorted-wave-born approximation with random-phase approximation transition densities indicates that the L = 0 multipolarity dominates the cross section for the ISGMR and significantly contributes to the low-energy mode. The L=0 part of this low-energy mode, the soft monopole mode, is dominated by neutron excitations. This demonstrates the relevance of inelastic alpha scattering in inverse kinematics in order to probe both the ISGMR and isoscalar soft modes in neutron-rich nuclei.

Continuing evolution of equine influenza virus in Central Asia, 2007-2012.

Equine influenza (EI) continues to be an important respiratory pathogen of horses worldwide. Since 2007 several outbreaks of EI have occurred in Central Asian countries, including Kazakhstan, western Mongolia, India and western China. Phylogenetic analysis showed that two H3N8 equine influenza virus (EIV) isolates from Kazakhstan, A/equine/Almaty/26/2007 and A/equine/South Kazakhstan/236/12, were related to Florida sublineage 2, with high similarity to EIVs circulating in the same period in neighbouring countries. New outbreaks of EI during 2011 and 2012 in Kazakhstan and other Central Asian countries were caused by viruses of the same lineage. Genetic characterization of the viruses showed formation of a small EIV cluster with specific genetic signatures and continued evolution of this lineage in Central Asia between 2007 and 2012. The main genetic changes were observed in hemagglutinin gene without any antigenic drift. Although no vaccination policy was carried out in Kazakhstan, application of Florida clade 2-based vaccines is recommended.

Needle Biopsy of Pleura in the Aetiological Diagnosis of Pleural Effusion.

Exudative pleural effusion appears as manifestation of underlying specific disease process and pleural biopsy is usually enough to find out the underlying causative disease. The aim of the study was to find out the efficacy of needle biopsy of pleura in the aetiological diagnosis of pleural effusion. This cross-sectional study was conducted for a period of one year from January 2008 to December 2008 in the Department of Medicine, Shaheed Ziaur Rahman Medical College Hospital, Bogura, Bangladesh enrolling 50 subjects with exudative pleural effusion. The cases with transudative pleural effusion were not included. Needle biopsy was done in all the cases. Histopathological reports of pleural biopsy specimen were correlated with other data and analyzed to detect the causes of effusion. Major incidence of malignant effusion occurred between 41 to 70 years of age. No malignant effusion was found before 30 years of age. Incidence of tuberculous and malignant pleural effusion was much more common in males than in females. Sensitivity and specificity of combined pleural biopsy and pleural fluid analysis in the diagnosis of pleural effusion was 97.06% and 100.% for tuberculosis and 81.82% and 100.0% for malignancy. The present study reveals that pleural biopsy was very effective method in the diagnosis of cause of pleural effusion.

The role of sheet-like TiO2 in polyamide reverse osmosis membrane for enhanced removal of endocrine disrupting chemicals.

Thin film composite (TFC) reverse osmosis (RO) membrane shows good promise for treating wastewater containing endocrine disrupting chemical (EDC) pollutants. The incorporation of functional materials with exceptional structural and physico-chemical properties offers opportunities for the membranes preparation with enhanced permselectivity and better antifouling properties. The present study aims to improve the EDC removal efficiency of TFC RO membrane using two-dimensional titania nanosheets (TNS). RO membrane was prepared by incorporating TNS in the dense layer of polyamide (PA) layer to form thin film nanocomposite (TFN) membrane. The TNS loading was varied and the influences on membrane morphology, surface hydrophilicity, surface charge, as well as water permeability and rejection of EDC were investigated. The results revealed that the inclusion of TNS in the membrane resulted in the increase of water permeability and EDC rejection. When treating the mixture of bisphenol A (BPA) and caffeine at 100 ppm feed concentration, the TFN membrane incorporated with 0.05% TNS achieved water permeability of 1.45 L/m2·h·bar, which was 38.6% higher than that of unmodified TFC membrane, while maintaining satisfactory rejection of >97%. The enhancement of water permeability for TFN membrane can be attributed to their hydrophilic surface and unique nanochannel structure created by the nanoscale interlayer spacing via staking of TiO2 nanosheets. Furthermore, the 0.05TFN membrane exhibited excellent fouling resistance towards BPA and caffeine pollutants with almost 100% flux recovery for three cycles of operations.

Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database.

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6-89.6) years with a median of 3 prior lines (range 1-9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1-5.6) months and 13.3 (95% CI 10.6-16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6-5.3) months and 10.5 (95% CI 8.5-13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Large hepatitis delta antigen activates STAT-3 and NF-κB via oxidative stress.

Hepatitis delta virus (HDV) coinfection or superinfection in hepatitis B virus (HBV)-infected patients results in a more aggressive liver disease, with more often fulminant forms and more rapid progression to cirrhosis and hepatocellular carcinoma. The mechanism(s) for this pejorative evolution remains unclear. To explore a specific HDV pathogenesis, we used a model of transient transfection of plasmids expressing the small (sHDAg or p24) or the large (LHDAg or p27) delta antigen in hepatocyte cell lines. We found that the production of reactive oxygen species was significantly higher in cells expressing p27. Consequently, p27 activated the signal transducer and activator of transcription-3 (STAT-3) and the nuclear factor kappa B (NF-κB) via the oxidative stress pathway. Moreover in the presence of antioxidants (PDTC, NAC) or calcium inhibitors (TMB-8, BAPTA-AM, Ruthenium Red), p27-induced activation of STAT-3 and NF-κB was dramatically reduced. Similarly, using a mutated form of p27, where the cysteine 211-isoprenylation residue was replaced by a serine, a significant reduction of STAT-3 and NF-κB activation was seen, suggesting the involvement of isoprenylation in this process. Additionally, we show that p27 is able to induce oxidative stress through activation of NADPH oxidase-4. These results provide insight into the mechanisms by which p27 can alter intracellular events relevant to HDV-related liver pathogenesis.

Constraining the nuclear equation of state at subsaturation densities.

Only one-third of the nucleons in 208Pb occupy the saturation density area. Consequently, nuclear observables related to the average properties of nuclei, such as masses or radii, constrain the equation of state not at the saturation density but rather around the so-called crossing density, localized close to the mean value of the density of nuclei: ρ is approximately equal to 0.11 fm(-3). This provides an explanation for the empirical fact that several equation of state quantities calculated with various functionals cross at a density significantly lower than the saturation one. The third derivative M of the energy per unit of volume at the crossing density is constrained by the giant monopole resonance measurements in an isotopic chain rather than the incompressibility at saturation density. The giant monopole resonance measurements provide M=1100±70 MeV (6% uncertainty), whose extrapolation gives K(∞)=230±40 MeV (17% uncertainty).