Improved overall survival in patients developing endocrine toxicity during treatment with nivolumab for advanced non-small cell lung cancer in a prospective study.

PURPOSE: Immune checkpoint inhibitors (ICPIs) disrupting PD-1/PD-L1 axis have revolutionized the management of advanced non-small cell lung cancer (NSCLC). Some studies identified the development of endocrine toxicity as predictor of better survival in cancer patients treated with ICPIs. The aim of study was to evaluate survival and new onset of immune-related endocrine adverse events (irAEs) in patients treated with nivolumab for advanced NSCLC. METHODS: In a prospective study, 73 patients with previously treated advanced NSCLC received nivolumab in monotherapy. Blood samples were collected at each cycle to monitor thyroid autoimmunity, thyroid, adrenal and somatotroph axes, while thyroid morphology was evaluated by ultrasonography. RESULTS: An impaired thyroid function was recorded in 23.4% of patients (n = 15). Eight patients developed asymptomatic transient thyrotoxicosis (ATT) evolving to hypothyroidism in 50% of cases. In addition, seven patients developed overt hypothyroidism without ATT and with negative autoantibodies. Patients who developed hypothyroidism proved to have better overall survival (OS) as compared with non-developers at both univariate (p = 0.021) and multivariate analyses (p = 0.023). The survival curve of patients with reduced IGF-I at baseline, or displaying its reduction during the follow-up, showed significantly reduced median survival compared to patients with normal/high IGF-I levels (p = 0.031). CONCLUSIONS: Thyroid function abnormalities are the major irAEs in patients treated with nivolumab, and hypothyroidism onset is associated with prolonged survival. Our findings indicate that the development of hypothyroidism is a positive predictive biomarker of nivolumab antitumor efficacy in patients with NSCLC. Low IGF-I levels could represent a negative prognostic factor during nivolumab therapy.

CAMKK2 is upregulated in primary human osteoarthritis and its inhibition protects against chondrocyte apoptosis.

OBJECTIVE: To investigate the role of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in human osteoarthritis. MATERIALS AND METHODS: Paired osteochondral plugs and articular chondrocytes were isolated from the relatively healthier (intact) and damaged portions of human femoral heads collected from patients undergoing total hip arthroplasty for primary osteoarthritis (OA). Cartilage from femoral plugs were either flash frozen for gene expression analysis or histology and immunohistochemistry. Chondrocyte apoptosis in the presence or absence of CAMKK2 inhibition was measured using flow cytometry. CAMKK2 overexpression and knockdown in articular chondrocytes were achieved via Lentivirus- and siRNA-mediated approaches respectively, and their effect on pro-apoptotic and cartilage catabolic mechanisms was assessed by immunoblotting. RESULTS: CAMKK2 mRNA and protein levels were elevated in articular chondrocytes from human OA cartilage compared to paired healthier intact samples. This increase was associated with elevated catabolic marker matrix metalloproteinase 13 (MMP-13), and diminished anabolic markers aggrecan (ACAN) and type II collagen (COL2A1) levels. OA chondrocytes displayed enhanced apoptosis, which was suppressed following pharmacological inhibition of CAMKK2. Levels of MMP13, pSTAT3, and the pro-apoptotic marker BAX became elevated when CAMKK2, but not its kinase-defective mutant was overexpressed, whereas knockdown of the kinase decreased the levels of these proteins. CONCLUSIONS: CAMKK2 is upregulated in human OA cartilage and is associated with elevated levels of pro-apoptotic and catabolic proteins. Inhibition or knockdown of CAMKK2 led to decreased chondrocyte apoptosis and catabolic protein levels, whereas its overexpression elevated them. CAMKK2 may be a therapeutic target to prevent or mitigate human OA.

Development of a Framework for the Communication System Based on KNX for an Interactive Space for UX Evaluation.

Domotics (Home Automation) aims to improve the quality of life of people by integrating intelligent systems within inhabitable spaces. While traditionally associated with smart home systems, these technologies have potential for User Experience (UX) research. By emulating environments to test products and services, and integrating non-invasive user monitoring tools for emotion recognition, an objective UX evaluation can be performed. To achieve this objective, a testing booth was built and instrumented with devices based on KNX, an international standard for home automation, to conduct experiments and ensure replicability. A framework was designed based on Python to synchronize KNX systems with emotion recognition tools; the synchronization of these data allows finding patterns during the interaction process. To evaluate this framework, an experiment was conducted in a simulated laundry room within the testing booth to analyze the emotional responses of participants while interacting with prototypes of new detergent bottles. Emotional responses were contrasted with traditional questionnaires to determine the viability of using non-invasive methods. Using emulated environments alongside non-invasive monitoring tools allowed an immersive experience for participants. These results indicated that the testing booth can be implemented for a robust UX evaluation methodology.

FACTORS AFFECTING RESEARCH ENGAGEMENT AMONG CLINICIANS IN AZARE, BAUCHI STATE, NIGERIA.

Introduction/Background: Medical research is a key element in the advancement of medicine and patient care improvement. However, there is evidence that developing regions like Nigeria have comparatively low research output. Clinicians' attitudes, practices, and barriers toward research are key causal factors of the low research productivity. Objectives: This study explored the research practice, attitude, and barriers towards research engagement among Clinicians at Federal Medical Centre, Azare, Bauchi state. Methodology: This was a quantitative cross-sectional study conducted at Federal Medical Centre, Azare, Bauchi state. Data on sociodemographic characteristics, research practices, attitudes, and barriers toward research engagement was obtained using a pretested, self-administered questionnaire. Data was collated and analyzed using IBM Statistical Package for Social Sciences software (SPSS) version 21. Result: A total of 101 clinicians participated in this study of which 14.9%, 31.7%, and 29.7% were Consultants, Registrars and Medical Officers respectively. Only 20.8% of the respondents have presented at a scientific conference previously, while 18.8% of the respondents have a published paper in a scientific journal. Although clinicians showed a positive attitude towards research (Mean: 4.39, SD ± 0.61), lack of research funding, facilities, mentorship, and demanding clinical services are major deterrents to clinicians' engagement in research. Conclusion: Clinicians have poor research practice despite their positive attitude towards research engagement. Appropriate interventions should be implemented for effective research engagement to augment research output.

Profile of Acute Poisoning among Adult Patients at the Emergency Room of a Tertiary Hospital, South-western Nigeria.

BACKGROUND AND OBJECTIVE: Acute poisoning often presents as an acute medical condition necessitating prompt medical care. Few data exist on adult poisoning and management protocol often are inadequate. Assessing the cases may inform a more robust protocol for case management, necessitating this study. The objective was to assess cases of acute poisoning and determine the agents as well as their outcomes. METHODS: This was a retrospective study involving 53 adult cases of acute poisoning at the emergency room (ER) of a tertiary hospital over 5 years (2016­2020). The ER register was assessed for the gender, type of agent and outcome of the medical condition. Cases admitted to the ward were followed up to determine their outcomes. RESULTS: There were more males, 34 (64.2%) than females. 19 (35.8%) with a mean age of 29.2 ± 13.5 years and 24.6 ± 8.2 years respectively. Organophosphates accounted for 22 (41.5%) of cases followed by a cocktail of unknown mixture in 12 (22.6%) and paraquat in 6 (11.3%) cases. Alcohol, medications, and alkali were responsible for 5 (9.5%), 4 (7.5%) and 4 (7.5%) cases respectively. Mortality was recorded in 11 (20.8%) of cases this was mostly associated with paraquat. In addition, 1 (1.9%) case was referred to another facility while 2 (3.8%) cases required longer hospital stay. More than 50% of the cases were discharged within 24 to 48 hours while 6 (11.3%) cases were discharged against medical advice. CONCLUSION: Organophosphate appears to be the most common agent responsible for acute poisoning in adults in this environment and young male adults have a higher risk. Most of the poisoning cases were discharged however, mortality was high, particularly among those with paraquat poisoning.

CONTEXTE ET OBJECTIF: L'intoxication aiguë se présente souvent comme une condition médicale aiguë nécessitant des soins médicaux rapides. Il existe peu de données sur l'empoisonnement chez les adultes et le protocole de gestion est souvent inadéquat. L'évaluation des cas peut éclairer un protocole plus robuste pour la gestion des cas, ce qui nécessite cette étude. L'objectif estd'évaluer les cas d'intoxication aiguë et de déterminer les agents ainsi que leurs résultats. MÉTHODES: Il s'agissait d'une étude rétrospective portant sur tous les cas d'intoxication aiguë auxurgences d'un hôpital tertiairesur une période de 5 ans (2016-2020). Le registre des urgences a été évalué pour le sexe, le type d'agent et l'issue de l'état de santé. Les cas renvoyés au service ont fait l'objet d'un suivi pour déterminer les résultats. RÉSULTATS: La proportion de bières était plus élevée que celle des femmes (64,2 % contre 35,8 %) avec un âge moyen de 29,2 ±13,5 ans et 24,6 ±8,2 ans respectivement. L'organophosphate représentait 41,5 % des cas, suivi du mélange cocktail (22,6 %) et du paraquat (11,3 %). L'alcool, les drogues et les alcalis étaient responsables de 9,4 %, 7,6 % et 7,5 % respectivement. Mortalité wtelle qu'enregistrée dans 20. 8 % des cas; 1,9 % ont été référés tandis que 3,8 % ont dû rester plus longtemps à l'hôpital. Plus de 50 % des cas ont reçu leur congé dans les 24 à 48 heures, tandis que 11,3 % ont reçu leur congé contre avis médical. Le paraquat était le plus souvent responsable de la mort, tandis que l'alcool, les alcalis et les opioïdes avaient le même taux de mortalité. Neuf (17,0 %) des 11 (20,8 %) mortalités étaient des hommes CONCLUSION: La mortalité par intoxication aiguë est élevée et l'empoisonnement au paraquat est l'agent le plus mortel suivi par l'organophosphate. Les jeunes hommes sont prédisposés à l'empoisonnement par l'organophosphate ou le paraquat pour lesquels la mortalité est élevée. Mots-clés: Empoisonnement, Paraquat, Urgence, Organophosphate, MMortalité.

Incidence and sociodemographic, living environment and maternal health associations with stillbirth in a tertiary healthcare setting in Kano, Northern Nigeria.

BACKGROUND: Almost two million stillbirths occur annually, most occurring in low- and middle-income countries. Nigeria is reported to have one of the highest stillbirth rates on the African continent. The aim was to identify sociodemographic, living environment, and health status factors associated with stillbirth and determine the associations between pregnancy and birth factors and stillbirth in the Murtala Mohammed Specialist Hospital, Kano, Nigeria. METHODS: A three-month single-site prospective observational feasibility study. Demographic and clinical data were collected. We fitted bivariable and multivariable models for stillbirth (yes/no) and three-category livebirth/macerated stillbirth/non-macerated stillbirth outcomes to explore their association with demographic and clinical factors. FINDINGS: 1,998 neonates and 1,926 mothers were enrolled. Higher odds of stillbirth were associated with low-levels of maternal education, a further distance to travel to the hospital, living in a shack, maternal hypertension, previous stillbirth, birthing complications, increased duration of labour, antepartum haemorrhage, prolonged or obstructed labour, vaginal breech delivery, emergency caesarean-section, and signs of trauma to the neonate following birth. INTERPRETATION: This work has obtained data on some factors influencing stillbirth. This in turn will facilitate the development of improved public health interventions to reduce preventable deaths and to progress maternal health within this site.

Telomere length dynamics over 10-years and related outcomes in patients with COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been proposed as a disease of accelerated aging. Several cross-sectional studies have related a shorter telomere length (TL), a marker of biological aging, with COPD outcomes. Whether accelerated telomere shortening over time relates to worse outcomes in COPD patients, is not known. METHODS: Relative telomere length (T/S) was determined by qPCR in DNA samples from peripheral blood in 263 patients at baseline and up to 10 years post enrolment. Yearly clinical and lung function data of 134 patients with at least two-time measures of T/S over this time were included in the analysis. RESULTS: At baseline, T/S inversely correlated with age (r = - 0.236; p < 0.001), but there was no relationship between T/S and clinical and lung function variables (p > 0.05). Over 10 years of observation, there was a median shortening of TL of 183 bp/year for COPD patients. After adjusting for age, gender, active smoking and mean T/S, patients that shortened their telomeres the most over time, had worse gas exchange, more lung hyperinflation and extrapulmonary affection during the follow-up, (PaO2 p < 0.0001; KCO p = 0.042; IC/TLC p < 0.0001; 6MWD p = 0.004 and BODE index p = 0.009). Patients in the lowest tertile of T/S through the follow-up period had an increased risk of death [HR = 5.48, (1.23-24.42) p = 0.026]. CONCLUSIONS: This prospective study shows an association between accelerated telomere shortening and progressive worsening of pulmonary gas exchange, lung hyperinflation and extrapulmonary affection in COPD patients. Moreover, persistently shorter telomeres over this observation time increase the risk for all-cause mortality.

Predictive Value of Clinical and Magnetic Resonance Image Findings in the Diagnosis of Meniscal and Anterior Cruciate Ligament Injuries.

BACKGROUND: Anterior Cruciate Ligament (ACL) injuries may be accompanied by associated injuries such as meniscal injuries. Clinical evaluation alone may at times miss the diagnosis of ACL injury and one or more associated injuries. However, an adjuvant diagnostic tool such as an MRI of the knee may be unaffordable to some patients. The goal of this study was to compare the sensitivity, specificity and predictive value of clinical and magnetic resonance image (MRI) findings in the diagnosis of anterior cruciate ligament and meniscal injuries. METHODS: This was a prospective study. The cases of ACL injury recruited had a magnetic resonance imaging of the injured knee, and knee arthroscopy done. The clinical, magnetic resonance imaging and arthroscopic diagnostic findings were all noted. The sensitivity, specificity, positive predictive value and negative predictive values of clinical and MRI findings were compared, with arthroscopic findings as gold standard. RESULTS: A total of seventy-seven patients were recruited for the study. There were fifty-four males and twenty three females. The results of the tests of the sensitivity, specificity, positive predictive value and negative predictive value of clinical diagnosis and MRI when compared with arthroscopy findings, in detecting meniscal and anterior cruciate ligament injuries were as follows: For Clinical evaluation; Anterior Cruciate ligament: 81%, 80%, 86% and 76%; Medial Meniscus: 84%, 77%, 84% and 93%; and Lateral Meniscus: 85%, 77%, 85% and 82% respectively. For MRI: Anterior Cruciate Ligament (ACL): 87%, 89%, 93% and 78% ; Medial Meniscus: 87% 79%, 70% and 82%; and the Lateral Meniscus: 70%, 76% 73% and 72%. CONCLUSION: The specificity, sensitivity and predictive value of clinical and MRI findings were comparable in relation to the diagnosis of ACL and Medial Meniscus tears. However, the values of these parameters were better with clinical examination than with MRI in relation to the diagnosis of lateral meniscus tears.

High Viral Hepatitis Infection among Pregnant Women Attending Antenatal Clinic in Adeoyo Maternity Teaching Hospital Ibadan (AMTHI) Oyo State, Nigeria.

Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Hepatitis E Virus (HEV) are highly endemic in several African countries including Nigeria with adverse effects on pregnancy outcomes resulting in fatality. This study aimed to determine the viral hepatitis in pregnant women attending antenatal clinic, AMTHI. Informed consent questionnaire was administered before blood collection via venipuncture. a total of 904 pregnant women plasma samples were tested for HBV, HCV, and HEV using ELISA kit. Data was analyzed using packages within SPSS software and P ≤ 0.05 was considered significant. Out of 904 samples analyzed, the overall prevalence of hepatitis infections among pregnant women attending antenatal clinic in AMTHI was 66(7.3%). High prevalence of the hepatitis infections was found among young women within the age group 21-30 which might be associated with active sex, intravenous drug use, sharing of sharp objects and alcoholism. Blood group O Positive had the highest prevalence of hepatitis. There was statistical significance between blood group and HBsAg infection (P < .05). Genotype AA women had highest prevalence of hepatitis. This study showed significant association between HBsAg, HCV, and HEV positive status with blood group O positive and Genotype AA pregnant women.

Preterm Babies: Management and Challenges Associated with Survival in a Resource-Limited Setting.

BACKGROUND: Preterm babies have constituted a major constraints on human and material resources due to early mortality and long term disability among survivors. Rates of disability among survivors have increased over the period, with high rates of broncho-pulmonary dysplasia. OBJECTIVE: To determine the survival and management challenges of preterm babies in University of Maiduguri Teaching Hospital, Maiduguri Borno State REUSLTS: Of the 1129 preterm babies managed in the Special Care Baby Unit (SCBU), 714 cases notes were retrieved and analyzed giving a retrieval rate of 63%. There were 256 (35.9%) preterm babies as in-born, while 458 (64.1%) were out-born. Male preterm babies were 372 (52.1%), while female preterm babies were 342 (47.9%); with female to male ratio of 1.08:1. Extreme low birth weight (<1000grams) were 17 (2.3%), very low birth weight (1000-1499 grams) were 288 (40.3%) while low birth weight (1500-2499 grams) were 406 (56.9%). We also documented 3 preterm babies whose weights >2500 grams were large for gestational age weight. Duration of oxygen therapy (p = 0.620), duration of phototherapy (p = 0.474), and EBT (p = 0.466) showed no association with their survival while only duration of incubator care (p = 0.005) demonstrated significant association with outcome. CONCLUSION: The population of preterm babies studied is 32.70% and their survival has remarkably improved. However, this improved survival of preterm babies especially the extreme and very low birth weight categories has posed a big challenge due to limited access to incubator care, use of caffeine and surfactant which might influence the outcome.

Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial.

BACKGROUND: Treatment options are limited for patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) following progression after first-line platinum-based therapy, particularly in Asian countries. PATIENTS AND METHODS: In this randomised, open-label, phase III trial, we enrolled Asian patients aged ≥18 years, with histologically or cytologically confirmed recurrent/metastatic HNSCC following first-line platinum-based therapy who were not amenable for salvage surgery or radiotherapy, and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients were randomised (2 : 1) to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week), stratified by ECOG performance status and prior EGFR-targeted antibody therapy. The primary end point was progression-free survival (PFS) assessed by an independent central review committee blinded to treatment allocation. RESULTS: A total of 340 patients were randomised (228 afatinib; 112 methotrexate). After a median follow-up of 6.4 months, afatinib significantly decreased the risk of progression/death by 37% versus methotrexate (hazard ratio 0.63; 95% confidence interval 0.48-0.82; P = 0.0005; median 2.9 versus 2.6 months; landmark analysis at 12 and 24 weeks, 58% versus 41%, 21% versus 9%). Improved PFS was complemented by quality of life benefits. Objective response rate was 28% with afatinib and 13% with methotrexate. There was no significant difference in overall survival. The most common grade ≥3 drug-related adverse events were rash/acne (4% with afatinib versus 0% with methotrexate), diarrhoea (4% versus 0%), fatigue (1% versus 5%), anaemia (<1% versus 5%) and leukopenia (0% versus 5%). CONCLUSIONS: Consistent with the phase III LUX-Head & Neck 1 trial, afatinib significantly improved PFS versus methotrexate, with a manageable safety profile. These results demonstrate the efficacy and feasibility of afatinib as a second-line treatment option for certain patients with recurrent or metastatic HNSCC. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01856478.

The role of CEA, CYFRA21-1 and NSE in monitoring tumor response to Nivolumab in advanced non-small cell lung cancer (NSCLC) patients.

BACKGROUND: CEA, CYFRA21-1 and NSE are tumor markers used for monitoring the response to chemotherapy in advanced adenocarcinoma, squamous cell carcinoma and small-cell lung cancer, respectively. Their role in cancer immunotherapy needs to be elucidated. METHODS: Patients with advanced non-small cell lung cancer (NSCLC) were treated with nivolumab 3 mg/kg every 2 weeks within the Italian Nivolumab Expanded Access Program. Blood samples were collected at baseline, at each cycle up to cycle 5 and then every two cycles until patient's withdrawn from the study. All patients underwent a CT-scan after every 4 cycles of treatment and responses were classified according to RECIST 1.1. The biomarkers serum levels were measured with a chemiluminescent microparticle immunoassay for CEA and with an immuno radiometric assay for CYFRA21-1 and NSE. The markers values at baseline and after 4 cycles were used to analyze the relationship between their variation over baseline and the tumor response, evaluated as disease control rate (DCR: CR + PR + SD), and survival (PFS and OS). RESULTS: A total of 70 patients were evaluable for the analysis. Overall, a disease control was obtained in 24 patients (35.8%, 4 PR + 20 SD). After 4 cycles of nivolumab a CEA or CYFRA21-1 reduction ≥ 20% over the baseline was significantly associated with DCR (CEA, p = 0.021; CYFRA21-1, p < 0.001), PFS (CEA, p = 0.028; CYFRA21-1, p < 0.001) and OS (CEA, p = 0.026; CYFRA21-1, p = 0.019). Multivariate analysis confirmed the ability of CYFRA21-1 reduction ≥ 20% to predict DCR (p = 0.002) and PFS (p < 0.001). CONCLUSION: The reduction in serum level of CYFRA21-1 or CEA might be a reliable biomarker to predict immunotherapy efficacy in NSCLC patients. NSE was not significant for monitoring the efficacy of nivolumab.

8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages.

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.

Balanced nutrient requirements for maize in the Northern Nigerian Savanna: Parameterization and validation of QUEFTS model.

Establishing balanced nutrient requirements for maize (Zea mays L.) in the Northern Nigerian Savanna is paramount to develop site-specific fertilizer recommendations to increase maize yield, profits of farmers and avoid negative environmental impacts of fertilizer use. The model QUEFTS (QUantitative Evaluation of Fertility of Tropical Soils) was used to estimate balanced nitrogen (N), phosphorus (P) and potassium (K) requirements for maize production in the Northern Nigerian Savanna. Data from on-farm nutrient omission trials conducted in 2015 and 2016 rainy seasons in two agro-ecological zones in the Northern Nigerian Savanna (i.e. Northern Guinea Savanna "NGS" and Sudan Savanna "SS") were used to parameterize and validate the QUEFTS model. The relations between indigenous soil N, P, and K supply and soil properties were not well described with the QUEFTS default equations and consequently new and better fitting equations were derived. The parameters of maximum accumulation (a) and dilution (d) in kg grain per kg nutrient for the QUEFTS model obtained were respectively 35 and 79 for N, 200 and 527 for P and 25 and 117 for K in the NGS zone; 32 and 79 for N, 164 and 528 for P and 24 and 136 for K in the SS zone; and 35 and 79 for N, 199 and 528 for P and 24 and 124 for K when the data of the two zones were combined. There was a close agreement between observed and parameterized QUEFTS predicted yields in each of the agro-ecological zone (R2 = 0.69 for the NGS and 0.75 for the SS). Although with a slight reduction in the prediction power, a good fit between the observed and model predicted grain yield was also detected when the data for the two agro-ecological zones were combined (R2 = 0.67). Therefore, across the two agro-ecological zones, the model predicted a linear relationship between grain yield and above-ground nutrient uptake until yield reached about 50 to 60% of the yield potential. When the yield target reached 60% of the potential yield (i.e. 6.0 t ha-1), the model showed above-ground balanced nutrient uptake of 20.7, 3.4 and 27.1 kg N, P, and K, respectively, per one tonne of maize grain. These results suggest an average NPK ratio in the plant dry matter of about 6.1:1:7.9. We concluded that the QUEFTS model can be widely used for balanced nutrient requirement estimations and development of site-specific fertilizer recommendations for maize intensification in the Northern Nigerian Savanna.

Adsorption of arsenic using chitosan magnetic graphene oxide nanocomposite.

Chitosan-magnetic-graphene oxide (CMGO) nanocomposite was prepared for arsenic adsorption. The nanocomposite was characterized through BET, FTIR, FESEM, EDX, and VSM analyses. These characterizations confirmed the formation of CMGO nanocomposites with high specific surface area (152.38 m2/g) and excellent saturation magnetization (49.30 emu/g). Batch adsorption experiments were conducted to evaluate the performance of the nanocomposite in the adsorption of arsenic from aqueous solution. The effects of operational parameters, adsorption kinetic, equilibrium isotherm and thermodynamics were evaluated. The removal efficiency of arsenic increased with increasing adsorbent dosage and contact time. However, the effect of pH followed a different pattern, with the removal efficiency increasing from acidic to neutral pH, and then decreasing at alkaline conditions. The highest adsorption capacity (45 mg/g) and removal efficiency (61%) were obtained at pH 7.3. The adsorption kinetic followed a pseudo-second-order kinetic model. The analysis of adsorption isotherm shows that the adsorption data fitted well to Langmuir isotherm model, indicating a homogeneous process. Thermodynamic analysis shows that the adsorption of As(III) is exothermic and spontaneous. The superparamagnetic properties of the nanocomposite enabled the separation and recovery of the nanoparticles using an external magnetic field. Thus, the developed nanocomposite has a potential for arsenic remediation.

Experimental evidence of spatial signatures of approaching regime shifts in macroalgal canopies.

Developing early warning signals to predict regime shifts in ecosystems is a central issue in current ecological research. While there are many studies addressing temporal early warning indicators, research into spatial indicators is far behind, with field experiments even more rare. Here, we tested the performance of spatial early warning signals in an intertidal macroalgal system, where removal of algal canopies pushed the system toward a tipping point (corresponding to approximately 75% of canopy loss), marking the transition between a canopy- to a turf-dominated state. We performed a two-year experiment where spatial early warning indicators were assessed in transects where the canopy was differentially removed (from 0 to 100%). Unlike Moran correlation coefficient at lag-1, spatial variance, skewness, and spatial spectra at low frequency increased along the gradient of canopy degradation and dropped, or did not show any further increase beyond the transition point from a canopy- to a turf-dominated state (100% canopy removal). Our study provides direct evidence of the suitability of spatial early warning signals to anticipate regime shifts in natural ecosystems, emphasizing the importance of field experiments as a powerful tool to establish causal relationships between environmental stressors and early warning indicators.

Serum proteomic test in advanced non-squamous non-small cell lung cancer treated in first line with standard chemotherapy.

BACKGROUND: VeriStrat is a blood-based proteomic test with predictive and prognostic significance in second-line treatments for non-small cell lung cancer (NSCLC). This trial was designed to investigate the role of VeriStrat in first-line treatment of advanced NSCLC with standard chemotherapy. Here we present the results for 76 non-squamous patients treated with a combination of carboplatin or cisplatin with pemetrexed. METHODS: The test-assigned classifications of VeriStrat Good or VeriStrat Poor to samples collected at baseline. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and objective response. Exploratory analyses of end points separately in carboplatin/pemetrexed and cisplatin/pemetrexed subgroups were also conducted. RESULTS: Patients classified as VeriStrat Good had longer PFS and OS than VeriStrat Poor: 6.5 vs 1.6 months and 10.8 vs 3.4 months, respectively; the corresponding hazard ratios (HRs) were 0.36 (P<0.0001) and 0.26 (P<0.0001); they were also more likely to achieve objective response. Prognostic significance of VeriStrat was confirmed in multivariate analysis. Significant differences in OS and PFS between Veristrat classifications were also found when treatment subgroups were analysed separately. CONCLUSIONS: The trial demonstrated clinical utility of VeriStrat as a prognostic test for standard first-line chemotherapy of non-squamous advanced NSCLC.

Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the Boston Birth Cohort.

BACKGROUND/OBJECTIVES: The intergenerational association of obesity may be driven by mother-to-newborn transmission of microbiota at birth. Yet cesarean delivery circumvents newborn acquisition of vaginal microbiota, and has been associated with greater childhood adiposity. Here we examined the independent and joint associations of maternal pre-pregnancy body mass index (BMI; kg m-2) and delivery mode with childhood overweight or obesity. SUBJECTS/METHODS: We prospectively followed 1441 racially and ethnically diverse mother-child dyads in the Boston Birth Cohort until age 5 years (range: 2.0-8.0 years). We used logistic regression to examine the independent and joint associations of delivery mode (cesarean and vaginal delivery) and pre-pregnancy BMI with childhood overweight or obesity (age-sex-specific BMI ⩾85th percentile). RESULTS: Of 1441 mothers, 961 delivered vaginally and 480 by cesarean. Compared with vaginally delivered children, cesarean delivered children had 1.4 (95% confidence interval (CI) 1.1-1.8) times greater odds of becoming overweight or obese in childhood, after adjustment for maternal age at delivery, race/ethnicity, education, air pollution exposure, pre-pregnancy BMI, pregnancy weight gain and birth weight. Compared with children born vaginally to normal weight mothers, after multivariable adjustment, odds of childhood overweight or obesity were highest in children born by cesarean delivery to obese mothers (odds ratio (OR): 2.8; 95% CI: 1.9-4.1), followed by children born by cesarean delivery to overweight mothers (OR: 2.2; 95% CI: 1.5-3.2), then children born vaginally to obese mothers (OR: 1.8; 95% CI: 1.3-2.6) and finally children born vaginally to overweight mothers (OR: 1.7; 95% CI: 1.2-2.3). CONCLUSIONS: In our racially and ethnically diverse cohort, cesarean delivery and pre-pregnancy overweight and obesity were associated with childhood overweight or obesity. Needed now are prospective studies that integrate measures of the maternal and infant microbiome, and other potentially explanatory covariates, to elucidate the mechanisms driving this association and to explore whether exposure to vaginal microbiota in cesarean delivered newborns may be an innovative strategy to combat the intergenerational cycle of obesity.

Biofilm is associated with chronic streptococcal meningoencephalitis in fish.

Biofilms are aggregates of attached microbial organisms whose existence on tissues is often recognised as a mechanism for the establishment of most chronic diseases. Herein we investigated the ability of piscine Streptococcus agalactiae, an important aquatic pathogen, for adaptation to this sessile lifestyle in vitro and in the brain of a tilapia fish model. Piscine S. agalactiae exhibited a weak attachment to polystyrene plates and expressed a low biofilm phenotype under the study conditions. Furthermore, fluorescent in situ hybridization and confocal laser scanning microscopy revealed discrete aggregates of attached S. agalactiae within brain tissues and around meningeal surfaces. They were embedded in an exopolysaccharide containing matrix, intractable to inflammatory response and showed some level of resistance to penicillin despite proven susceptibility on sensitivity test. Intracellular bacterial aggregates were also observed, moreover, antibody mediated response was not demonstrated during infection. Nucleated erythrocytes appear to facilitate brain invasion possibly via the Trojan horse mechanism leading to a granulomatous inflammation. We have demonstrated that biofilm is associated with persistence of S. agalactiae and the development of chronic meningoencephalitis in fish.

Electrocoagulation treatment of raw landfill leachate using iron-based electrodes: Effects of process parameters and optimization.

The main problem of landfill leachate is its diverse composition comprising many persistent organic pollutants which must be removed before being discharge into the environment. This study investigated the treatment of raw landfill leachate using electrocoagulation process. An electrocoagulation system was designed with iron as both the anode and cathode. The effects of inter-electrode distance, initial pH and electrolyte concentration on colour and COD removals were investigated. All these factors were found to have significant effects on the colour removal. On the other hand, electrolyte concentration was the most significant parameter affecting the COD removal. Numerical optimization was also conducted to obtain the optimum process performance. Under optimum conditions (initial pH: 7.73, inter-electrode distance: 1.16 cm, and electrolyte concentration (NaCl): 2.00 g/L), the process could remove up to 82.7% colour and 45.1% COD. The process can be applied as a pre-treatment for raw leachates before applying other appropriate treatment technologies.