Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation

Efficient Co-Utilization of Biomass-Derived Mixed Sugars for Lactic Acid Production by <i>Bacillus coagulans</i> Azu-10

Lignocellulosic and algal biomass are promising substrates for lactic acid (LA) production. However, lack of xylose utilization and/or sequential utilization of mixed-sugars (carbon catabolite repression, CCR) from biomass hydrolysates by most microorganisms limits achievable titers, yields, and productivities for economical industry-scale production. This study aimed to design lignocellulose-derived substrates for efficient LA production by a thermophilic, xylose-utilizing, and inhibitor-resistant Bacillus coagulans Azu-10. This strain produced 102.2 g/L of LA from 104 g/L xylose at a yield of 1.0 g/g and productivity of 3.18 g/L/h. The CCR effect and LA production were investigated using different mixtures of glucose (G), cellobiose (C), and/or xylose (X). Strain Azu-10 has efficiently co-utilized GX and CX mixture without CCR; however, total substrate concentration (>75 g/L) was the only limiting factor. The strain completely consumed GX and CX mixture and homoferemnatively produced LA up to 76.9 g/L. On the other hand, fermentation with GC mixture exhibited obvious CCR where both glucose concentration (>25 g/L) and total sugar concentration (>50 g/L) were the limiting factors. A maximum LA production of 50.3 g/L was produced from GC mixture with a yield of 0.93 g/g and productivity of 2.09 g/L/h. Batch fermentation of GCX mixture achieved a maximum LA concentration of 62.7 g/L at LA yield of 0.962 g/g and productivity of 1.3 g/L/h. Fermentation of GX and CX mixture was the best biomass for LA production. Fed-batch fermentation with GX mixture achieved LA production of 83.6 g/L at a yield of 0.895 g/g and productivity of 1.39 g/L/h

Potential impact of tomosynthesis on the detection and diagnosis of breast lesi

Objective: The aim of this study was to evaluate the clinical performance of 3D tomosynthesis in comparison with Full Field Digital Mammography (FFDM) in the detection and diagnosis of breast lesions. Material and methods: 132 patients underwent standard digital mammography and tomosynthesis and the likelihood of malignancy was categorized according to (ACR) BI-RADS. Results: Tomosynthesis images had significantly increased the number of cases with BI-RAD 1 or 2 (normal/benign) to 62 (42.7%) compared to 39 (26.8%) at mammogram (p < 0.005). Tomosynthesis helped also in more clarification of benign characters. Tomosynthesis images had significantly decreased the number of indeterminate/suspicious lesions (BI-RADS 3 and 4) from 90 (62%) cases to 39 (26.8%) (p < 0.005). In a total of 40 lesions (27.5%) assigned to BI-RADS 5 at tomosynthesis, the tomosynthesis showed better performance in assessment of tumor extension and higher level in detection of clusters of micro-calcifications. The accuracy, specificity, sensitivity and positive and negative predictive values (%) of mammography alone versus when combined with the tomosynthesis were as follows: 59.3, 62.8, 55.2, 56 and 62 versus 91.7, 92.3, 91, 91, and 92.3 respectively (Table 4). Tomosynthesis significantly improved the detection of the breast lesions on mammography images especially in the dense breast with significantly higher accurate BI-RADS scoring (P value <0.005). Conclusion: Breast tomosynthesis is a promising technology that offers improved diagnostic and screening accuracy, fewer recalls as well as 3D lesion localization. Lesion conspicuity is improved using DBT compared with FFDM with a more confidence in making clinical decisions

The clinical value of ultrasound elastography in predicting malignant thyroid nodules

Objective: This study aims to evaluate the clinical value of ultrasound elastography (USE) in providing information on the nature of the thyroid nodules. This was performed using the elastography score and strain ratio in differentiating thyroid benign and malignant nodules and the histopathological examination was used as the diagnostic standard of reference. Methods: We examined 84 thyroid nodules in 62 patients with ultrasound elastography. Elastography score was assigned based on a four-point scale according to the classification proposed by Itoh et al. with a score of 1 (low stiffness over the entire nodule) to a score of 4 (high stiffness over the entire nodule). Thyroid strain ratio (normal tissue to lesion strain ratio) was calculated. Histopathological results were the standard reference. The area under the curve (AUC) and the best cut-off point were both obtained using receiver-operating characteristic (ROC) curve analysis. The sensitivity, specificity, and accuracy of both techniques were calculated. Results: Fifty-four of the 84 nodules had scores of 1 and 2, and 50 of these nodules were diagnosed histopathologically as benign. Thirty of the 84 nodules had a score of 3 and 4, and 21 of these nodules were diagnosed histopathologically as malignant. The scores of 1 and 2 with Itoh criteria were significantly seen in benign nodules, whereas, scores of 3 and 4 were significantly seen in malignant nodules (p < 0.05) with sensitivity 84%, specificity 84.7%, PPV 70%, NPV 92.6% and accuracy 84.5%. The mean SR for the benign nodules and malignant ones was significantly different (2.92 ± 0.96 vs. 4.53 ± 0.82, p < 0.001). With ROC analysis, the best cut-off strain ratio point was 3.5 for differentiating benign and malignant nodules with area under the curve (AUC) = 0.87 (0.8–0.95). The sensitivity of the strain ratio was 88%, while the specificity was 86.4%, PPV = 73.3%, NPV = 94.4% and accuracy = 86.9%. Conclusions: Both the elastographic score and strain ratio are higher in malignant nodules than those in benign ones. Ultrasound elastography can provide quantitative information on thyroid nodule helping in differentiating benign and malignant ones

The sarcolemmal calcium pump, alpha-1 syntrophin, and neuronal nitric-oxide synthase are parts of a macromolecular protein complex.

The main role of the plasma membrane Ca2+/calmodulin-dependent ATPase (PMCA) is in the removal of Ca2+ from the cytosol. Recently, we and others have suggested a new function for PMCA as a modulator of signal transduction pathways. This paper shows the physical interaction between PMCA (isoforms 1 and 4) and alpha-1 syntrophin and proposes a ternary complex of interaction between endogenous PMCA, alpha-1 syntrophin, and NOS-1 in cardiac cells. We have identified that the linker region between the pleckstrin homology 2 (PH2) and the syntrophin unique (SU) domains, corresponding to amino acids 399-447 of alpha-1 syntrophin, is crucial for interaction with PMCA1 and -4. The PH2 and the SU domains alone failed to interact with PMCA. The functionality of the interaction was demonstrated by investigating the inhibition of neuronal nitric-oxide synthase-1 (NOS-1); PMCA is a negative regulator of NOS-1-dependent NO production, and overexpression of alpha-1 syntrophin and PMCA4 resulted in strongly increased inhibition of NO production. Analysis of the expression levels of alpha-1 syntrophin protein in the heart, skeletal muscle, brain, uterus, kidney, or liver of PMCA4-/- mice, did not reveal any differences when compared with those found in the same tissues of wild-type mice. These results suggest that PMCA4 is tethered to the syntrophin complex as a regulator of NOS-1, but its absence does not cause collapse of the complex, contrary to what has been reported for other proteins within the complex, such as dystrophin. In conclusion, the present data demonstrate for the first time the localization of PMCA1b and -4b to the syntrophin.dystrophin complex in the heart and provide a specific molecular mechanism of interaction as well as functionality

Seasonal dynamics and ecological risks of organochlorine pesticides in Kafrelsheikh-Egypt: Implications for aquatic ecosystems and public health

Kafrelsheikh, situated in the middle of the Nile Delta, significantly contributes to Egypt's aquaculture and agriculture sectors. However, the local use of organochlorine pesticides (OCPs) in agriculture is often a source of OCP residues in associated drainage waters, which may threaten aquatic ecosystems. These pesticides persist in local water bodies, jeopardizing aquatic ecosystems and potentially impacting human health. This comprehensive study assessed the seasonal variations of 17 OCPs in both water sources and Nile tilapia across eight fish farming locations in Kafrelsheikh. Using gas chromatography coupled with mass spectrometry (GC-MS), we detected OCP concentrations in water that varied seasonally where winter recorded the highest levels at 22.5 ng/mL and, summer showed the lowest levels at 6.2 ng/mL. Despite water samples occasionally showing risk quotients (RQs) greater than 1, indicating a potential threat to aquatic life, the OCP levels in Nile tilapia were sufficiently low, with target hazard quotients (THQ) below 1, suggesting no significant risk for human consumption. The research highlights a pressing need for regular environmental monitoring and stricter regulatory control over pesticide use to protect aquatic life and ensure the safety of aquaculture products. These findings provide a critical basis for policy-making, aimed at balancing agricultural productivity with environmental sustainability in regions heavily dependent on both

Concurrent radiochemotherapy versus surgery followed by radiotherapy for hypopharyngeal carcinoma: A single-center study

AbstractBackgroundHypopharyngeal cancer is a rare disease representing about 0.5% of all human malignancies and constituting only 3–5% of all head and neck cancer. Concurrent radiochemotherapy has been recommended as a standard of care in patients with locally advanced squamous cell head and neck carcinomas. There were very few reports about these tumors arising from North Africa.ObjecttiveThis work was a retrospective study at the Ain Shams University hospitals comparing induction chemotherapy and concomitant radiochemotherapy to surgery followed by radiotherapy as regards over all survival.MethodsThis study included 49 patients with hypopharyngeal carcinoma, twenty-three (46.93%) were treated surgically. Surgical excision of the tumor was by pharyngo-laryngo-esophagectomy, except for 2 patients treated by conservative surgery. Postoperative radiotherapy was given to all patients. Twenty sex patients (53.07%) were treated by induction chemotherapy and concomitant radiochemotherapy.ResultsThe mean age was 52.6years (range 25–82). In the present study, females (55.1%) dominated males (44.9%).The most commonly involved subsite, in this study, was the postcricoid area (31 patients=63.3%), followed by the pyriform sinus (16 patients=32.6%), while the posterior pharyngael wall was the site of origin in only two patients (4.1%). According to the AJCC-TNM staging system, 40 patients (81.6%) were advanced stages III and IV, while only 9 patients (18.4%) had an early presentation as stages I and II. Cox proportional-hazard regression was used to compare survival in the two study groups. There was no statistically significant difference in the failure function (death) between patients treated with concomitant radiochemotherapy or surgery followed by radiotherapy after adjusting for the age category, tumor grade, T stage and N stage (proportional hazard, 1.114; 95% CI, 0.574 to 2.163; P, 0.751).Of the variables included in the model, only N1 stage was an independent predictor for the hazard of death after adjusting for the treatment group, age category, tumor grade and T stage (proportional hazard, 2.321; 95% CI, 1.073–5.022; P, 0.033). The model had a −2 log likelihood (likelihood ratio statistic, LRS) of 277.316, which was not statistically significant (P, 0.0501) indicating adequate fit of the full model.ConclusionPostcricoid carcinoma comprises the majority of hypopharyngeal tumors in Egypt. Females are more commonly affected by these tumors, especially postcricoid carcinoma. There was no survival difference between the intended therapy for organ preservation and radical surgery groups. Patients who received concurrent radiochemotherapy had a better chance of survival with a preserved larynx compared with patients who underwent surgery

FGF21/FGFR1-β-KL cascade in cardiomyocytes modulates angiogenesis and inflammation under metabolic stress

Diabetes is a metabolic disorder with an increased risk of developing heart failure. Inflammation and damaged vasculature are the cardinal features of diabetes-induced cardiac damage. Moreover, systemic metabolic stress triggers discordant intercellular communication, thus culminating in cardiac dysfunction. Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone transducing cellular signals via fibroblast growth factor receptor 1 (FGFR1) and its co-receptor beta-klotho (β-KL). This study first demonstrated a decreased expression or activity of FGFR1 and β-KL in both human and mouse diabetic hearts. Reinforcing cardiac FGFR1 and β-KL expression can alleviate pro-inflammatory response and endothelial dysfunction upon diabetic stress. Using proteomics, novel cardiomyocyte-derived anti-inflammatory and proangiogenic factors regulated by FGFR1-β-KL signaling were identified. Although not exhaustive, this study provides a unique insight into the protective topology of the cardiac FGFR1-β-KL signaling-mediated intercellular reactions in the heart in response to metabolic stress