CPL-01, an investigational long-acting ropivacaine, demonstrates safety and efficacy in open inguinal hernia repair.

BACKGROUND: There is an unmet medical need for effective nonopioid analgesics that can decrease pain while reducing systemic opioid use. CPL-01, an extended-release injectable formulation of ropivacaine, is designed to safely provide analgesia and reduce or eliminate opioid use in the postoperative period. METHODS: Subjects undergoing open inguinal hernia with mesh were prospectively randomized to 1 of 3 doses of CPL-01 (10, 20, or 30 ml of 2% CPL-01, n = 14, 12, and 14, respectively), Naropin (150 mg, n = 40), or saline placebo (n = 13) infiltrated into the surgical site prior to closure. Pain and rescue medication usage was assessed, and Numeric Rating Scale (NRS) pain scores were adjusted for opioid usage using windowed worst observation carried forward (wWOCF) imputation. The primary efficacy endpoint was the mean area under the curve (AUC) of the NRS pain intensity scores with activity. RESULTS: Ninety-three subjects were treated, and 91 subjects completed 72 h of post-operative monitoring. Subjects who received the highest dose of CPL-01 in Cohort 3 showed a clinically meaningful reduction in postoperative pain intensity scores, which was the lowest value for any treatment in all cohorts, showing a trend towards statistical significance as compared to the pooled placebo group (p = 0.08), and numerically better than the 40 subjects who received Naropin. Opioid use through 72 h in subjects who received CPL-01 in Cohort 3 was approximately half of that shown in the placebo and Naropin groups; approximately 2/3 of the CPL-01 subjects (9/14) required no opioids at all through the first 72 h after the operation. More CPL-01 subjects avoided severe pain and were ready for discharge earlier than other groups. CPL-01 was safe and well-tolerated, with no clinically meaningful safety signals, and showed predictable and consistent extended-release pharmacokinetics. CONCLUSION: Results suggest that CPL-01 may be the first long-acting ropivacaine to address postoperative pain while reducing the need for opioids.

Effect of next-step antidepressant treatment on suicidal ideation: findings from the VAST-D trial.

BACKGROUND: Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. METHOD: The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. RESULTS: Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. CONCLUSION: SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

Parental education and youth suicidal behaviours: a systematic review and meta-analysis.

AIMS: Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations. METHODS: We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0-18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity. RESULTS: We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04-1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98-1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10-1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54-0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05-1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77-1.08). CONCLUSIONS: The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.

Axin2+ PDL Cells Directly Contribute to New Alveolar Bone Formation in Response to Orthodontic Tension Force.

Wnt-ß-catenin signaling plays a key role in orthodontic tooth movement (OTM), a common clinical practice for malocclusion correction. However, its targeted periodontal ligament (PDL) progenitor cells remain largely unclear. In this study, we first showed a synchronized increase in Wnt-ß-catenin levels and Axin2+ PDL progenitor cell numbers during OTM using immunostaining of ß-catenin in wild-type mice and X-gal staining in the Axin2-LacZ knock-in line. Next, we demonstrated time-dependent increases in Axin2+ PDL progenitors and their progeny cell numbers within PDL and alveolar bones during OTM using a one-time tamoxifen-induced Axin2 tracing line (Axin2CreERT2/+; R26RtdTomato/+). Coimmunostaining images displayed both early and late bone markers (such as RUNX2 and DMP1) in the Axin2Lin PDL cells. Conversely, ablation of Axin2+ PDL cells via one-time tamoxifen-induced diphtheria toxin subunit A (DTA) led to a drastic decrease in osteogenic activity (as reflected by alkaline phosphatase) in PDL and alveolar bone. There was also a decrease in new bone mass and a significant reduction in the mineral apposition rate on both the control side (to a moderate degree) and the OTM side (to a severe degree). Thus, we conclude that the Axin2+ PDL cells (the Wnt-targeted key cells) are highly sensitive to orthodontic tension force and play a critical role in OTM-induced PDL expansion and alveolar bone formation. Future drug development targeting the Axin2+ PDL progenitor cells may accelerate alveolar bone formation during orthodontic treatment.

Pressure induced superconductivity in MnSe.

The rich phenomena in the FeSe and related compounds have attracted great interests as it provides fertile material to gain further insight into the mechanism of high temperature superconductivity. A natural follow-up work was to look into the possibility of superconductivity in MnSe. We demonstrated in this work that high pressure can effectively suppress the complex magnetic characters of MnSe, and induce superconductivity with Tc ~ 5 K at pressure ~12 GPa confirmed by both magnetic and resistive measurements. The highest Tc is ~ 9 K (magnetic result) at ~35 GPa. Our observations suggest the observed superconductivity may closely relate to the pressure-induced structural change. However, the interface between the metallic and insulating boundaries may also play an important role to the pressure induced superconductivity in MnSe.

Tunable magnetic low-frequency noise in magnetic tunnel junctions: effect of shape anisotropy.

The intrinsic magnetic low-frequency noise (LFN) is of fundamental scientific interest to the study of magnetic tunnel junctions (MTJs). To gain insight into its mechanism, the fluctuation-dissipation theorem, which describes the linear relation between magnetic LFN and magnetic sensitivity product, has been utilized. However, deviation from the linear correlation has been reported in some studies. To understand and effectively control the magnetic LFN, a more elaborate analytical description and further experimental validation are required. In this work, the magnetic LFN contributed from the magnetization fluctuation in the pinned layer of MTJs with various shape anisotropies was investigated. The MTJs with different shape anisotropies, achieved by altering their aspect ratios, possessed distinct demagnetizing factors. Large magnetic noise was correlated with the increase of magnetic phase loss of ferromagnetic layers during magnetization reversal at which magnetization fluctuation was enhanced. Upon increasing the shape anisotropy, a notable reduction of the magnetic phase loss in the antiparallel (AP) state was observed while it exhibited a slight decrease in the parallel (P) state, revealing that the increase of the shape anisotropy caused a more pronounced suppression of the equilibrium magnetization fluctuation in the AP state. These phenomena were computationally validated by constructing a macrospin model to describe the thermally-induced magnetization fluctuation in the pinned layer. This work reveals the physical relation between MTJ shape anisotropy and magnetic LFN. The effect of the shape anisotropy on the magnetic LFN can be extended to other types of in-plane uniaxial anisotropies.

[Total neoadjuvant therapy followed by watch and wait approach or organ preservation for MRI stratified low-risk rectal cancer: early result from a prospective, single arm trial].

Objective: To explore the safety and efficacy of watch and wait strategy and organ preservation surgery after total neoadjuvant treatment for MRI stratified low-risk rectal cancer. Methods: A prospective single arm phase Ⅱ trial developed at Department of Gastrointestinal Cancer, Peking University Cancer Hospital & Institute was preliminarily analyzed. Subjects were enrolled from August 2016 to January 2019. Low-risk rectal cancer with following MRI features were recruited: mid-low tumor, mrT2-3b, MRF (-), EMVI (-), CRM (-), differentiation grade 1-3. Patients received intensity-modulated radiotherapy (IMRT) 50.6 Gy/22f with concurrent capecitabine and 4 cycles of consolidation CAPEOX. Patients with cCR/near-cCR confirmed by physical examination, rectal MRI, endoscopy, and serum CEA were recommended for watch & wait approach or local excision (LE). The main study outcomes were 2-year organ preservation rate (OPR) and sphincter preservation rate (SPR). Results: Thirty-eight patients were eligible for analysis, including 24 males and 14 females with median age of 56 years; 9 cases of mrT2 (23.7%), 14 cases of mrT3a (36.8%) and 15 cases of mrT3b (39.5%); 5 cases of well differentiated adenocarcinoma (13.2%), 32 cases of moderately differentiated adenocarcinoma (84.2%) and 1 case of mucinous adenocarcinoma (2.6%). Carcinoemobryonic antigen (CEA) was elevated before treatment in 1 case. One case (2.6%) of grade 3 radiation dermatitis occurred during IMRT; 18 cases (47.4%) occurred grade 3 to 4 adverse events during consolidation chemotherapy. After total neoadjuvant treatment, the cCR and near-cCR rates were 42.1% (16/38) and 23.7% (9/38), respectively, while non-cCR rate was 34.2% (13/38). Twenty patients (20/38, 52.6%) of cCR or near-cCR underwent watch & wait approach, with a local regrowth rate of 20% (4/20). Four patients received LE, including one salvage LE. Thirteen patients (4 were ypCR) received radical resection, including 10 cases of initial low anterior resections (LAR), 1 cases of initial abdominal perineal resection (APR) and 2 cases of salvage LAR, four patients refused operation. The median follow-up time was 23.5 (8.5-38.3) months. At the last interview of follow-up, the OPR and SPR were 52.6% (20/38) and 84.2% (32/38), respectively. Only one patient developed lung metastasis and no local recurrence occurred after radical resection or LE. Conclusion: Total neoadjuvant treatment for low-risk rectal cancer achieves high cCR/near-cCR rate, with increased probability of receiving watch and wait approach and organ preservation in this subgroup.

[Short-term outcomes and prognosis of palliative surgery for malignant bowel obstruction caused by peritoneal metastasis of colorectal cancer].

Objective: To explore the short-term efficacy and prognosis of palliative surgical treatment for malignant bowel obstruction (MBO) caused by peritoneal metastasis of colorectal cancer (mCRC). Methods: A retrospective cohort study was conducted. The inclusion criteria for patients were as follows: (1) primary colorectal cancer; (2) massive peritoneal metastasis; (3)obstructive site located below Treitz ligament by imaging; (4) obstruction refractory to conservative treatment; (5) estimated rese survival time more than 2 months; (6) patients and their families had strong willingness for operation; (7) surgical treatment included stoma/bypass and debulking surgery. In accordance with the above criteria, clinicopathological data of 46 patients undergoing palliative surgery at Peking University Gastrointestinal Cancer Center, Unit III from January 2016 to October 2018 were retrospectively collected. Postoperative symptomatic relief rate, morbidity of complication within 30 days, complication classification (Clavien-Dindo classification), mortality and survival after operation were analyzed. Kaplan-Meier method was used to evaluate survival and Cox regression analysis was used to identify prognostic factors. Results: Among 46 patients, 30 were male and 16 were female with median age of 63 (19-87) years; 23 patients received stoma/bypass surgery (stoma/bypass group), and 23 cases received tumor debulking surgery (debulking group). The overall symptom relief rate was 76.1% (35/46), while symptom relief rate in the debulking group was 91.3% (21/23), which was significantly higher than 60.9% (14/23) in the stoma/bypass group (χ(2)=4.301, P=0.038). Postoperative complications occurred in 25 patients. The complication rate was 52.2% (12/23) in the debulking group and 56.5% (13/23) in the stoma/bypass group, without statistically significant difference (χ(2)=0.088, P=0.767). Morbidity of complication beyond grade III was 8.7% (2/23) and 13.0% (3/23) in the debulking group and stoma/bypass group respectively, without statistically significant difference (χ(2)=0.224, P=0.636). Four patients died within 30 days after operation, 2 (8.7%) in each group. Twenty-four patients underwent 1-8 cycles of chemotherapy ± targeting therapy (regimens: CapeOX ± Bevacizumab, FOLFOX/FOLFIRI ± Bevacizumab/Cetuximab), including 10 cases in the stoma/bypass group and 14 cases in the debulking group. Two patients of debulking group received postoperative radiotherapy and chemotherapy (50.6 Gy/22 f, with concurrent oral capecitabine). Till the last follow up of April 2019, 34 patients died (34/46, 73.9%) with a median overall survival time of 6.4 months, and the 6-month and 1-year survival rate was 54.5% and 29.2% respectively. The median survival time in the debulking group was significantly longer than that in the stoma/bypass group (11.5 months vs. 5.2 months, χ(2)=5.117, P=0.024). The median survival time of the 35 patients with symptomatic relief after operation was significant longer than that of 11 patients without relief (7.1 months vs 5.1 months, χ(2)=3.844, P=0.050). Multivariate analysis showed stoma/bypass surgery (HR=2.917, 95%CI:1.357-6.269, P=0.006) and greater omental metastasis (HR=4.060, 95%CI:1.419-11.617, P=0.009) were independent risk factors associated with prognosis of patients with MBO caused by peritoneal mCRC. Conclusions: For patients of MBO caused by peritoneal mCRC, tumor debulking surgery may achieve higher symptom relief rate and prolong survival. Greater omental metastasis indicates poor prognosis.

["Watch and wait" strategy after neoadjuvant therapy for rectal cancer: status survey of perceptions, attitudes and treatment selection in Chinese surgeons].

Objective: To understand the perceptions, attitudes and treatment selection of Chinese surgeons on the "watch and wait" strategy for rectal cancer patients after achieving a clinical complete response (cCR) following neoadjuvant chemoradiotherapy (nCRT). Methods: A cross-sectional survey was used in this study. Selection of subjects: (1) Domestic public grade III A (provincial and prefecture-level) oncology hospitals or general hospitals possessing the radiotherapy department and the diagnosis and treatment qualifications for colorectal cancer. (2) Surgeons of deputy chief physician or above. Using the "Questionnaire Star" online survey platform to create a questionnaire about cognition, attitude and treatment choice of the "watch and wait" strategy after cCR following nCRT for rectal cancer. The questionnaire contained 32 questions, such as the basic information of doctor, the current status of rectal cancer surgery, the management of pathological complete remission (ypCR) after nCRT for rectal cancer, the selection of examination items for diagnosis of cCR, the selection of suitable people undergoing "watch and wait" approach, the nCRT mode for promotion of cCR, the choice of evaluation time point, the willingness to perform "watch and wait" approach and the treatment choice, and the risk and monitoring of "watch and wait" approach. A total of 116 questionnaires were sent to the respondents via WeChat between January 31 and February 19, 2019. Statistical analysis was performed using Fisher's exact test for categorical variables. Results: Forty-eight hospitals including 116 surgeons meeting criteria were enrolled, of whom 77 surgeons filled the questionnaire with a response rate of 66.4%. "Watch and wait" strategy was carried out in 76.6% (59/77) of surgeons. Seventy surgeons (90.9%) were aware of the ypCR rate of rectal cancer after preoperative nCRT and 49 surgeons (63.6%) knew the 3-year disease-free survival of patients with ypCR in their own hospitals. Fifty-five surgeons (71.4%) believed that patients with ypCR undergoing radical surgery met the treatment criteria and were not over-treated. Three most necessary examinations in diagnosing cCR were colonoscopy (96.1%, 74/77), digital rectal examination (DRE) (90.9%,70/77) and DWI-MRI (83.1%, 64/77). Responders preferred to consider a "watch and wait" strategy for patients with baseline characteristics as mrN0 (77.9%, 60/77), mrT2 (68.8%, 53/77) and well-differentiated adenocarcinoma (68.8%, 53/77). Sixty-six surgeons (85.7%) believed that long-term chemoradiotherapy (LCRT) with combination or without combination of induction and/or consolidation of the CapeOX regimen (capecitabine + oxaliplatin) should be the first choice as a neoadjuvant therapy to achieve cCR. Forty-one surgeons (53.2%) believed that a reasonable interval of judging cCR after nCRT should be ≥ 8 weeks. Forty-four surgeons (57.1%) routinely, or in most cases, informed patient the possibility of cCR and proposed to "watch and wait" strategy in the initial diagnosis of patients with non-metastatic rectal cancer. Thirteen surgeons (16.9%) would take the "watch and wait" strategy as the first choice after the patient having cCR. Fifty-two surgeons (67.5%) would be affected by the surgical method, that was to say, "watch and wait" approach would only be recommended to those patients who would achieve cCR and could not preserve the anus or underwent difficult anus-preservation surgery. Sixteen surgeons (20.8%) demonstrated that "watch and wait" strategy would not be recommended to patients with cCR regardless of whether the surgical procedure involved anal sphincter. Eleven surgeons (14.3%) believed that the main risk of "watch and wait" approach came from distant metastasis rather than local recurrence or regrowth. Twenty-nine of surgeons (37.7%) did not understand the difference between "local recurrence" and "local regrowth" during the period of "watch and wait". Twenty-six surgeons (33.8%) thought that the monitoring interval for the first 3 years of "watch and wait" strategy was 3 months, and the follow-up monitoring interval could be 6 months to 5 years. Surgeons from cancer specialist hospitals had higher approval rate, notification rate, and referral rate of "watch and wait" strategy than those from general hospitals. Thirty-one surgeons (42.5%) considered that the difficulty and concern of carrying out "watch and wait" approach in the future was the disease progress leading to medical disputes. Twenty-six surgeons (35.6%) demonstrated that their concern was lack of uniform evaluation standard for cCR. Conclusions: Chinese surgeons seem to have inadequate knowledge of non-operative management for rectal cancer patients achieving cCR after nCRT and show relatively conservative attitudes toward the strategy. Chinese consensus needs to be formed to guide the non-operative management in selected patients. Chinese Watch & Wait Database (CWWD) is also needed to establish and provide more evidence for the use of alternative procedure after a cCR following nCRT.

More efficient North Atlantic carbon pump during the Last Glacial Maximum.

During the Last Glacial Maximum (LGM; ~20,000 years ago), the global ocean sequestered a large amount of carbon lost from the atmosphere and terrestrial biosphere. Suppressed CO2 outgassing from the Southern Ocean is the prevailing explanation for this carbon sequestration. By contrast, the North Atlantic Ocean-a major conduit for atmospheric CO2 transport to the ocean interior via the overturning circulation-has received much less attention. Here we demonstrate that North Atlantic carbon pump efficiency during the LGM was almost doubled relative to the Holocene. This is based on a novel proxy approach to estimate air-sea CO2 exchange signals using combined carbonate ion and nutrient reconstructions for multiple sediment cores from the North Atlantic. Our data indicate that in tandem with Southern Ocean processes, enhanced North Atlantic CO2 absorption contributed to lowering ice-age atmospheric CO2.

Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection.

BACKGROUND: Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human immunodeficiency virus (HIV) coinfection. AIM: To evaluate the effectiveness and safety of generic VEL/SOF-based therapy for HCV infection in patients with or without HIV coinfection in Taiwan. METHODS: Sixty-nine HIV/HCV-coinfected and 159 HCV-monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti-viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12 ) were analysed. RESULTS: The SVR12 was achieved in 67 HIV/HCV-coinfected patients (97.1%; 95% CI: 90.0%-99.2%) and in 156 HCV-monoinfected patients (98.1%; 95% CI: 94.6%-99.4%) receiving VEL/SOF-based therapy, respectively. The SVR12 rates were comparable between HIV/HCV-coinfected and HCV-monoinfected patients, regardless of pre-specified baseline characteristics. One hundred twenty-two (53.5%) and seven (3.1%) patients had baseline resistance-associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV-coinfected and HCV-monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV-coinfected patients receiving anti-retroviral therapy containing tenofovir disoproxil fumarate (TDF). CONCLUSIONS: Generic VEL/SOF-based therapy is well-tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.

Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection.

BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.

Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Annealing Stability Study of Co20Fe60B20\MgO\ Co20Fe60B20 Perpendicular Magnetic Tunnel Junctions.

A full Co20Fe60B20\MgO\ Co20Fe60B20 perpendicular magnetic tunnel junction (pMTJ) with (Co\Pt) multilayers as pinning layers and different functional multilayers stacks were made and annealed at different temperatures. The tunneling magnetoresistance ratio (TMR) and MgO barrier resistance-area product (RA) were measured and analyzed as a function of annealing temperature. The TMR of pMTJs dramatically declines with increasing annealing temperatures from 320 °C to 400 °C while the RA increases with temperature from 375 °C to 450 °C. The pMTJs and partial stacks were also measured in a vibrating sample magnetometer (VSM). We found that the (Co\Pt) multilayers are very stable and maintain a magnetization direction perpendicular to the film plane up to 450 °C. However, the magnetization direction of the CoFeB above and below the MgO barrier rotates from perpendicular to in-plane with increasing annealing temperature. Furthermore, the CoFeB layer influences the adjacent (Co\Pt) layers to rotate at the same time. The pMTJs' elemental depth profiles in the as deposited and annealed states were determined by Secondary Ion Mass Spectrometry (SIMS). We found that Boron and Tantalum migrate towards the top of the stack. The other elements (Platinum, Cobalt, Ruthenium, and Magnesium) are very stable and do not interdiffuse during annealing up to 450°C.