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Background The optimal time for initiation of dialysis and which modality to choose as the starting therapy is currently unclear. This systematic review aimed to assess the recommendations across high-quality clinical practice guidelines (CPGs) related to the start of dialysis. Methods We systematically searched MEDLINE, EMBASE, Web of Science, LILACS, and databases of organisations that develop CPGs between September 2008 to August 2021 for CPGs that addressed recommendations on the timing of initiation of dialysis, selection of dialysis modality, and interventions to support the decision-making process to select a dialysis modality. We used the Appraisal of Guidelines for Research and Evaluation instrument to assess the methodological quality of the CPGs and included only high-quality CPGs. This study is registered in PROSPERO, number CRD42018110325. Results We included 12 high-quality CPGs. Six CPGs addressed recommendations related to the timing of initiating dialysis, and all agreed on starting dialysis in the presence of symptoms or signs. Six CPGs addressed recommendations related to the selection of modality but varied greatly in their content. Nine CPGs addressed recommendations related to interventions to support the decision-making process. Eight CPGs agreed on recommended educational programs that include information about dialysis options. One CPG considered using patient decision aids a strong recommendation. Limitations We could have missed potentially relevant guidelines since we limited our search to CPGs published from 2008, and we set up a cut-off point of 60% in domains of the rigour of development and editorial independence. Conclusion High-quality CPGs related to the process of starting dialysis were consistent in initiating dialysis in the presence of symptoms or signs and offering patients education at the point of decision-making. There was variability in how CPGs addressed the issue of dialysis modality selection. CPGs should improve strategies on putting recommendations into practice and the quality of evidence to aid decision-making for patients. Registration The protocol of this systematic review has been registered in the international prospective register of systematic reviews (PROSPERO) under the registration number: CRD CRD42018110325. https://clinicaltrials.gov/ct2/show/CRD42018110325.

Additional file 4: Figure S4. Relative Wolbachia densities (ankyrin repeat domain to rps17) in the ovaries, carcass and eggs of Ae. aegypti in replicate group 2. A Wolbachia densities in the eggs vs the ovaries of Ae. aegypti in replicate group 2. B. Wolbachia densities in the eggs vs the carcass of Ae. aegypti in replicate group 2. n = 18 individuals.

Additional file 7: Figure S7. Relative Wolbachia densities (ankyrin repeat domain to rps17) in the ovaries and the carcass of Ae. aegypti in the same generation of daughters (F1). n = 79, P = 0.21 (paired t-test). Bars indicate tissue means ± SE. ns, Not significant.

Additional file 5: Figure S5. Crossing point values of rps17 in the tissues of mothers (P1) and daughters (F1). These data pertain to Fig. 6 in the main text. A Crossing point values of rps17 of P1 in Ae. aegypti. B Crossing point values of rps17 of F1 in Ae. aegypti. Figure A has n = 31 individuals while B has n = 78 individuals. Bars indicate tissue means ± SE; ****P ≤ 0.0001.

Additional file 3: Figure S3. Relative Wolbachia densities (ankyrin repeat domain to rps17) in the ovaries, carcass and eggs of Ae. aegypti in replicate group 2. One-way ANOVA P

Additional file 1: Figure S1. Crossing point values of rps17 in the ovaries and the carcass of Ae. aegypti in the same generation of mothers (P1). These data pertain to Fig. 2 in the main text. n = 206, P

Additional file 8: Figure S8. Relationship between relative Wolbachia densities in the ovaries and the carcass of Ae. aegypti in the same generation of daughters (F1). n = 79.

Additional file 6: Figure S6. Crossing point values of rps17 in the eggs of mothers (P1) and tissues of daughters (F1). These data pertain to Fig. 7 in the main text. For P1 eggs n = 20 individuals, while for ovaries and carcass n = 94 individuals. Bars indicate tissue means ± SE. ns, Not significant; asterisks indicate significant difference at ****P ≤ 0.0001.

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC. ispartof: NPJ BREAST CANCER vol:7 issue:1 ispartof: location:United States status: published

COVID-19 has resulted in extraordinarily challenging times. The outbreak has disrupted the lives of people and is casting a heavy impact on the economies around the world by interrupting business operations and commercial activities. Whilst everyone is busy identifying various strategies from short term and medium to long term to overcome the recession, the future projects a blurry picture at least for the moment. A study group consisting of eminent persons recently submitted a report to the President containing recommendations aimed at steering Sri Lanka into a post-COVID-19 era of economic recovery. One of the recommendations was on Trade Agreements. The suggestion includes action to revive and accelerate the negotiation of a trade partnership agreement with China; an expanded agreement with India; an agreement with Thailand and with other Asian countries particularly other ASEAN members including Japan and to maximize the benefits from the Agreement already entered with Singapore. In this backdrop, the question arises as to whether the existing laws in Sri Lanka on Trade and Anti-Dumping are sufficient to protect the domestic traders and domestic industries against any possible unfair trading practices and the possibility of an unforeseen surge of imports which may arise with the signing of more Bilateral and Regional Trade Agreements. An attempt is made in this article to examine the key features and the effectiveness of the provisions of the legislation passed by the Parliament in 2018 on Anti-Dumping and to identify the protective measures that are sought to be introduced under the same. The Anti-Dumping & Countervailing Duties Act, No. 2 of 2018, and the Safeguard Measures Act, No. 3 of 2018 were certified by the Speaker of the Sri Lankan Parliament in March 2018. The enactment of these two laws was to remedy a need to answer the grievances of domestic producers and manufacturers. The official statement issued by the Ministry of Industry and Commerce on the occasion stipulates that Sri Lanka has taken a fairly long time to introduce the relevant legislation. This article proceeds to consider some of the salient features of the Anti-Dumping & Countervailing Duties Act, No. 2 of 2018 (the Anti-Dumping Act of 2018 Act) namely: (1) Part I of the Anti-Duping Act of 2018 on Anti-Dumping Duties, (2) the procedural steps in investigations under Part I on Anti-Dumping (3) Part II of the Anti-Duping Act of 2018 Act on Countervailing Duties, and (4) the procedural steps in investigations under Part II on Countervailing Duties. The Anti-Dumping Act of 2018 contains significant noteworthy features. Firstly, the act attempts to strike a balance between competing interests. The Right to Information on one hand and the economic value of sensitive trade-related information on the other. Secondly, the Act specifies timeframes for inquiries and related procedural steps recognizing the importance of resolving trade-related disputes in an effective, efficient, and efficacious manner. Thirdly the Act lays down a systematic procedure that ensures a fair opportunity be given to all parties with provision for public interest intervention. In terms of methodology, this article strictly adopts a doctrinal approach; doctrinal since the article proceeds to engage in an analysis of the law as it is on the four areas identified above. The enactment of these two laws will significantly improve the country’s standing in global trade and Sri Lanka will join the league of World Trade Organization - WTO members who keenly look to offset possible adverse impacts on their domestic industries from trade liberalization processes. The Gazette Notification making the Anti Dumping Law operable was issued on the 09th of October 2020 and the law is in force from 10 Oct 2020. The order by the Minister under section 01 was published in the Gazzetta Extraordinary No. 2197/4 – dated 12th October 2020. Both the laws on paper appear to be comprehensive. Yet the levels of effectiveness can be evaluated only when the Act stands the test of time. The reason/s for the delay in making the law operational is unclear. Section 84(1) of the Anti-Dumping Act authorizes the Minister to make regulations in respect of all matters required by the Act; the hold may be attributable to the formulation of the regulations. It may also be due to the setting up of infrastructure to facilitate the holding of inquiries, arming the officials with the necessary expertise for the successful implementation of the Act, or the contemplation of changes in policy and the introduction of further amendments to the already enacted laws. The effectiveness and/or whether the existing laws are sufficient to protect the domestic producers in the event of a surge of imports is debatable. The existing laws at the moment are not operational and the effectiveness is yet to stand the test of time. At the same time, the need to further consider strengthening the laws to protect domestic industries and producers whilst entering into more Trade Agreements cannot be undermined.

Background Polypharmacy interventions are resource-intensive and should be targeted to those at risk of negative health outcomes. Our aim was to develop and internally validate prognostic models to predict health-related quality of life (HRQoL) and the combined outcome of falls, hospitalisation, institutionalisation and nursing care needs, in older patients with multimorbidity and polypharmacy in general practices. Methods Design two independent data sets, one comprising health insurance claims data (n=592 456), the other data from the PRIoritising MUltimedication in Multimorbidity (PRIMUM) cluster randomised controlled trial (n=502). Population: ≥60 years, ≥5 drugs, ≥3 chronic diseases, excluding dementia. Outcomes: combined outcome of falls, hospitalisation, institutionalisation and nursing care needs (after 6, 9 and 24 months) (claims data); and HRQoL (after 6 and 9 months) (trial data). Predictor variables in both data sets: age, sex, morbidity-related variables (disease count), medication-related variables (European Union-Potentially Inappropriate Medication list (EU-PIM list)) and health service utilisation. Predictor variables exclusively in trial data: additional socio-demographics, morbidity-related variables (Cumulative Illness Rating Scale, depression), Medication Appropriateness Index (MAI), lifestyle, functional status and HRQoL (EuroQol EQ-5D-3L). Analysis: mixed regression models, combined with stepwise variable selection, 10-fold cross validation and sensitivity analyses. Results Most important predictors of EQ-5D-3L at 6 months in best model (Nagelkerke’s R² 0.507) were depressive symptoms (−2.73 (95% CI: −3.56 to −1.91)), MAI (−0.39 (95% CI: −0.7 to −0.08)), baseline EQ-5D-3L (0.55 (95% CI: 0.47 to 0.64)). Models based on claims data and those predicting long-term outcomes based on both data sets produced low R² values. In claims data-based model with highest explanatory power (R²=0.16), previous falls/fall-related injuries, previous hospitalisations, age, number of involved physicians and disease count were most important predictor variables. Conclusions Best trial data-based model predicted HRQoL after 6 months well and included parameters of well-being not found in claims. Performance of claims data-based models and models predicting long-term outcomes was relatively weak. For generalisability, future studies should refit models by considering parameters representing well-being and functional status.