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• Patients given combination amiodarone and beta-blockers had significantly lower risks of developing postoperative atrial fibrillation (POAF) in comparison to those given beta-blockers alone. • Combination amiodarone and beta-blockers saw no significant difference with beta-blockers alone in terms of treatment-related drug discontinuations (TRDD) or mortality. • Amiodarone alone saw no significant difference when compared with beta-blockers in terms of POAF prevention. Guideline recommendations regarding the preferred preventive measures for postoperative atrial fibrillation (POAF) are unclear, nor have we found any review articles addressing the combination of amiodarone and beta-blockers for the prevention of POAF. To investigate the efficacy and safety of combination beta-blockers and amiodarone in the prevention of POAF while also comparing the use of amiodarone and beta-blockers individually. We used Pubmed as the primary resource. POAF incidence was the primary outcome of this study. The secondary outcomes were hospital length of stay (LOS), ICU LOS, treatment-related drug discontinuation (TRDD), and mortality. The random-effects model assessed all pooled outcomes with 95% confidence intervals. Statistical significance was set at p ≤0.05. The amiodarone subgroup of POAF incidence saw a Risk Ratio (RR) of 0.81 [0.63, 1.06], p =0.12, while the combination subgroup resulted in a RR of 0.63 [0.49, 0.80], p <0.001. TRDD for the amiodarone subgroup resulted in a RR of 0.68 [0.25, 1.82], p =0.44, while the combination subgroup saw a RR of 0.84 [0.57, 1.23], p =0.36. For mortality, the amiodarone subgroup resulted in a RR of 0.97 [0.48, 1.98], p =0.93, while the combination subgroup resulted in a RR of 1.04 [0.27, 4.05], p =0.96. Both hospital and ICU LOS saw no significant difference between treatment arms for both the combination subgroup and amiodarone alone. Except for the incidence of postoperative atrial fibrillation (POAF) in the combination prophylaxis group, most of the measured outcomes did not meet the optimized information size (OIS) that was estimated. Combination prophylaxis with amiodarone and beta-blockers significantly lowered risks of POAF incidence in comparison to beta-blockers alone while also having comparative mortality and TRDD outcomes. [ABSTRACT FROM AUTHOR]

A substantial proportion of patients with heart failure and kidney disease have poorly controlled blood pressures. This study aimed to evaluate patterns of blood pressure after initiation of an angiotensin receptor neprilysin inhibitor (ARNI) or an angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) across the spectrum of kidney function. Between 2016 and 2020, we evaluated 26,091 patients admitted to a Veterans Affairs hospital for an acute heart failure exacerbation with reduced ejection fraction. We assessed patterns of systolic and diastolic blood pressure among those started on ARNI or ACEI/ARB over 6 months, overall and across estimated glomerular filtration rate (eGFR). To account for differential treatment factors, we applied 1:1 propensity score matching using 15 known baseline covariates. There were 13,781 individuals treated with an ACEI or ARB and 2589 individuals treated with an ARNI prescription. After propensity score matching, 839 patients were matched in each of the ARNI and ACEI/ARB groups. Mean baseline estimated glomerular filtration rate (eGFR) was 63.8 (standard deviation 21.6), and 10% had stage 4 or 5 chronic kidney disease. Patients in the ARNI group experienced greater systolic blood pressure reduction at month 3 (-5.2 mmHg vs -2.2 mmHg, ARNI vs ACEI/ARB; P < 0.001), and month 6 (-4.7 mmHg vs -1.85 mmHg, ARNI vs ACEI/ARB; P < 0.001). These differences in systolic blood pressure by 6 months did not vary by eGFR above and below 60 mL/min/1.73m2 or continuously across a wide range of eGFR (P interaction > 0.10 for both). The use of ARNI was associated with significant reduction in blood pressure as compared to the ACEI/ARB group overall and across the eGFR spectrum, including in advanced chronic kidney disease. [Display omitted] [ABSTRACT FROM AUTHOR]

• The use of balanced electrolyte solutions among patients with moderate to severe DKA is associated with faster resolution compared to isotonic saline. • Time to event analysis for the resolution of DKA adjusted for possible confounders such as baseline bicarbonate and volume of IV fluids are needed for future studies. Current guidelines suggest the use of isotonic saline (IS) infusion as the preferred resuscitation fluid in the management of diabetic ketoacidosis (DKA). However, balanced electrolyte solutions (BES) have been proposed as an alternative due to a lower propensity to cause hyperchloremic metabolic acidosis. Evidence regarding the use of BES in DKA remains limited. To determine if the use of BES in fluid resuscitation leads to faster resolution of DKA compared to IS. The study involves a comprehensive search of literature from PubMed, Cochrane CENTRAL, Google Scholar, and Science Direct of clinical trials addressing the use of BES vs IS in fluid resuscitation in DKA. The time to resolution of DKA was examined as the primary endpoint. Pooled hazard ratios (HR) and Mean Difference (MD) in hours with their 95% confidence intervals (CI) were calculated using a random-effects model. The literature search included 464 studies that were screened individually. A total of 9 studies were identified but 6 studies were excluded due to irrelevance in the outcome of interest and target population. The pooled hazard ratio HR significantly revealed 1.46 [1.10 to 1.94] (p = 0.009) with 12% heterogeneity while MD was -3.02 (95% CI -6.78–0.74; p = 0.12) with heterogeneity of 85%. Considering the evidence from pooled small randomized trials with moderate overall certainty of evidence, the use of BES in DKA was associated with faster rates of DKA resolution compared to IS. [ABSTRACT FROM AUTHOR]

• Small molecules have been proposed as alternatives to regenerate bone tissue. • Small molecule drug dose can often be reduced while still achieving effective therapeutic. • The potential to improve bone repair by making it safer, easier, and more cost-effective with the use of a small molecule delivered in the short-term. Osteogenic small molecules have been adapted as one of the encouraging approaches to regenerate bone tissue. Small molecules used long term will usually result in adverse effects. A novel approach is short-term treatment with osteogenic small molecules. Demonstrating effectiveness for regenerating bone with a short-term treatment or a single-dose administration of osteogenic small molecules could enhance safety by reducing adverse effects. Over the past few years, many small molecules with the potential of regenerating bone tissue have been reported when used for short-term or single-dose administration. Here, I review the relevant literature, paying particular attention to prospects for small molecule-mediated bone regeneration with short-term exposure. [ABSTRACT FROM AUTHOR]

Patients who had acute myocardial infarction are at high risk of negative cardiac outcomes and previous SGLT2i landmark trials excluded these patients. It therefore remains unclear if SGLT2i is safe and confers beneficial cardiovascular outcomes after acute myocardial infarction. We systematically reviewed randomized controlled trials that evaluated the outcomes of adding SGLT2i to conventional post-myocardial infarction care. Random-effects model meta-analysis via RevMan 5.4 was done on data extracted from pooled 11,204 patients. SGLT2i use after acute myocardial infarction was significantly associated with reduced heart failure hospitalization (OR: 0.77, 95%CI: 0.62–0.96, p =0.02), but was not associated with a reduction in all-cause mortality (OR: 1.05, 95%CI: 0.77–1.43, p =0.75), cardiac-related death (OR: 1.04, 95%CI: 0.83–1.30, p =0.76), or major adverse cardiac events (OR: 0.90, 95%CI: 0.77–1.05, p =0.18). SGLT2 inhibitor therapy after acute myocardial infarction is safe and is associated with a reduced risk of heart failure hospitalization, but not with all-cause mortality. [ABSTRACT FROM AUTHOR]

This paper develops a political perspective of just transition by linking the just transition concept with the concept of policy implementation, thereby drawing attention to the role of local policy implementers in the process and outcome of just transition. Focusing on the Chinese political context, it examines the degree of implementation flexibility in a broader context of authoritarian environmentalism. Implementation flexibility at the local level has been an enduring feature of Chinese environmental governance and can be considered as a key political process through which just transition can be achieved. However, recent studies suggest that the strengthening of top-down control over the environment means that the implementation process has become less flexible. Drawing on a case study of a logging town in the Greater Khingan Range transitioning under the National Forest Conservation Program, we found that while the strengthening of top-down control has resulted in an elevated level of compliance, flexibility remains an important dynamic in policy implementation. As such, local policy implementers still play an important role in just transition. This persistence of implementation flexibility is driven by a combination of local priorities, implementation difficulties, and top-down control. [ABSTRACT FROM AUTHOR]

• International eco-cities face unique governance challenges. • We examine Chinese international eco-cities from a multilevel governance perspective. • Multilevel governance provides possibilities for establishing bilateral cooperation. • Effectiveness of multilevel governance is conditioned by intermediary institutions. • Effectiveness also depends on maintaining the attention of national governments. International cooperation has become an important element of urban climate experimentation, particularly in developing countries. Using the Sino-German Eco-Park in Qingdao as a case study, we argue that while multilevel governance and international cooperation are often discussed separately, these two governance tendencies are in fact both important to China's urban climate experimentation. In particular, Chinese multilevel governance enables bilateral cooperation by (re)shaping the national vision at the local level and resolving potential conflicts or contradictions. It also allows local and foreign intermediaries to coordinate and match resources among different interests and actors. The effectiveness of multilevel governance in eco-city projects is conditioned by intermediary institutions' resources and capabilities. Effectiveness also depends on maintaining the attention of national governments to the eco-city projects. Thus, the cooperative form, the actors' attributes, and the resources mobilised by actors are three important factors that affect the outcomes of international eco-city projects. [ABSTRACT FROM AUTHOR]

There is no current standardized approach to anticoagulation in patients with Coronavirus Disease 2019 (COVID-19) while potential bleeding risks remain. Our study characterizes the patterns of anticoagulation use in COVID-19 patients and the risk of related bleeding. This is a single center retrospective analysis of 355 adult patients with confirmed diagnosis of COVID-19 from March 1 to May 31, 2020. Chi-square was used to analyze the relationship between degree of anticoagulant dose and bleeding events by site. Multivariable logistic regression was used to look at factors associated with inpatient death. 61% of patients were being treated with prophylactic doses of anticoagulation, while 7% and 29% were being treated with sub-therapeutic and therapeutic anticoagulation (TA) doses respectively. In 44% of patients, we found that the decision to escalate the dose of anticoagulation was based on laboratory values characterizing the severity of COVID-19 such as rising D-dimer levels. There were significantly higher rates of bleeding from non-CNS/non-GI sites (p = 0.039) and from any bleeding site overall (p = 0.019) with TA. TA was associated with significantly higher rates of inpatient death (41.6% vs 15.3% p < 0.0001) compared to those without. All patients who developed CNS hemorrhage died p = 0.011. After multivariable logistic regression, only age OR 1.04 95% CI (1.01 to 1.07) p = 0.008 and therapeutic anticoagulation was associated with inpatient mortality OR 6.16 95% CI (2.96 to 12.83) p ≤ 0.0001. The use of TA was significantly associated with increased risk of bleeding. Bleeding in turn exhibited trends towards higher inpatient death among patients with COVID-19. These findings should be interpreted with caution and larger more controlled studies are needed to verify the net effects of anticoagulation in patients with COVID-19. • Major bleeding is associated with use of therapeutic anticoagulation in COVID-19. • Therapeutic anticoagulation has shown higher mortality and major bleeding trends. • Risks and benefits of anticoagulation in COVID-19 should be weighed cautiously. [ABSTRACT FROM AUTHOR]

Background: As health-care institutions mobilize resources to address the coronavirus disease 2019 (COVID-19) pandemic, palliative care may potentially be underutilized. It is important to assess the use of palliative care in response to the COVID-19 pandemic.Methods: This is a retrospective single-center study of patients with COVID-19 diagnosed via reverse transcriptase-polymerase chain reaction assay admitted between March 1, 2020, and April 24, 2020. An analysis of the utilization of palliative care in accordance with patient comorbidities and other characteristics was performed while considering clinical outcomes. Chi-square test was used to determine associations between categorical variables while t-tests were used to compare continuous variables.Results: The overall mortality rate was 21.5% (n = 52), and in 48% (n = 25) of these patients, palliative care was not involved. Fifty-nine percent (n = 24) of those who had palliative consults eventually elected for comfort measures and transitioned to hospice care. Among those classified as having severe COVID-19, only 40% (n = 31) had palliative care involvement. Of these patients with severe COVID-19, 68% (n = 52) died. Patients who got palliative care consults were of older age, had higher rates of intubation, a need for vasopressors, and were dead.Conclusion: There was a low utilization rate of palliative care in patients with COVID-19. Conscious utilization of palliative care is needed at the time of COVID-19. [ABSTRACT FROM AUTHOR]

• Bicarbonate use in critically ill patients with high anion gap metabolic acidosis predominantly lactic acidosis did not show any significant mortality benefit. • There is weak evidence showing possible mortality benefit and improved renal outcomes especially in the subset of patients with acute kidney injury. • bicarbonate should be used with caution in the setting of concomitant respiratory acidosis as it may be associated with potential adverse effects. The use of sodium bicarbonate in the treatment of metabolic acidosis in critically ill subjects has long been a subject of debate. Despite empiric use in the setting of severe acidemia in critically ill patients, there is little data looking into the role of sodium bicarbonate in the treatment of severe metabolic acidosis in the intensive care unit (ICU) setting. We conducted a comprehensive search of Pubmed and Cochrane Central Register of Controlled Trials addressing bicarbonate use in the metabolic acidosis in the intensive care unit (ICU) setting. We examined mortality as end point. Pooled odds ratios (OR) and their 95% confidence intervals (CI) were calculated for all outcomes using a random-effect model. The final search yielded 202 articles of which all were screened individually. A total of 11 studies were identified but 6 studies were excluded due to irrelevance in mortality outcome and methodology. Analysis was done separately for observational studies and randomized controlled trials. The pooled OR [95% CI] for mortality with bicarbonate use in the observational studies was 1.5 [0.62–3.67] with heterogeneity of 67%, while pooled OR for mortality in the randomized trials was 0.72 [0.49–1.05] (figure 2). In combining all studies, the pooled odds ratio was 0.93 95% [0.69–1.25] but with heterogeneity of 63%. After sensitivity analysis with removing the study done by Kim et al. 2013, heterogeneity was 0% with OR 0.8 [0.59–1.10]. There is no significant difference in mortality in the use of bicarbonate among critically ill patients with high anion gap metabolic acidosis predominantly driven by lactic acidosis. [ABSTRACT FROM AUTHOR]

The possible cardiorenal relationship between pericarditis and the development of acute kidney injury (AKI) among patients admitted for acute decompensate Heart failure (HF) has not been explored. Concomitant pericarditis among patients hospitalized for HF might be associated with higher rates of AKI. We used STATA software to analyze the National Inpatient Sample (2016-2019) data of hospitalized decompensated HF patients classified as either with or without pericarditis. The primary outcome of interest was a diagnosis of AKI during admission. Secondary outcomes included all-cause mortality and length of stay. Multivariable logistic regression was done after adjustment for age, gender, comorbidities: COPD, hypertension, and chronic kidney disease (CKD) stage. A total of 1,590,199 primary HF hospitalizations were included in our analysis, with 2,621 developed pericarditis. The mean age was 71.5 ± 13.6, and females represented 48.7%. The majority had diastolic HF (53.3%), followed by systolic (34.3%) and combined HF (10.6%). About 33.9% of HF patients with pericarditis developed AKI. Multivariable logistic regression showed a significantly higher odds of AKI (aOR 1.90; 95%CI [1.75-2.07] p <0.001) overall mortality (aOR 2.26; 95%CI [1.95- 2.61] p <0.001) and length of stay (aOR 1.90, 95% CI [1.75 - 2.07] p <0.001) in pericarditis patients when compared to patients without pericarditis. Subgroup analysis showed significant results for AKI and LOS in all HF types, while the significant results for all-cause of mortality were significant only for diastolic HF (aOR 1.46; 95%CI [1.12 - 1.92] p =0.007). Pericarditis is associated with poor outcomes in hospitalized HF patients with higher associated rates of AKI, length of stay, and all-cause mortality. The cardiorenal association between pericarditis and AKI might be hypothesis-generating. [ABSTRACT FROM AUTHOR]

The economic restructuring of cities has a significant impact on their carbon emissions and is an important pathway to low-carbon development. China is the world’s largest carbon emitter, but few studies provide an in-depth analysis of how economic restructuring is affecting carbon emissions at its city level. This study develops a Stochastic Impacts by Regression on Population, Affluence and Technology (STIRPAT) model to analyze the impact of economic restructuring on CO 2 emissions in Shanghai. The results suggest that Shanghai’s emissions have remained stable post-2007, largely due to the city’s economic restructuring in favor of the tertiary sector: every 1% increase in the tertiary sector’s share of GDP is associated with a 0.76% reduction in CO 2 emissions. This study also uses a multi-objective genetic algorithm, specifically the Non-dominated Sorting Genetic Algorithm II (NSGA-II), to optimize economic restructuring of Shanghai with regard to economic and climate objectives. The result suggests that Shanghai should aim to reduce the industrial share of gross output from 49.4% in 2012 to 38.3% in 2020. The main conclusion of the study is that Shanghai and, by extension, other Chinese cities, cannot achieve their climate targets without making meaningful changes to the economy geared towards less carbon-intensive activities. [ABSTRACT FROM AUTHOR]

Musculoskeletal pain is a major health issue which results from surgical procedures (i.e. total knee and/or hip replacements and rotator cuff repairs), as well as from non-surgical conditions (i.e. sympathetically-mediated pain syndrome and occipital neuralgia). Local anesthetics, opioids or corticosteroids are currently used for the pain management of musculoskeletal conditions. Even though local anesthetics are highly preferred, the need for multiple administration presents significant disadvantages. Development of unique delivery systems that can deliver local anesthetics at the injection site for prolonged time could significantly enhance the therapeutic efficacy and patient comfort. The goal of the present study is to evaluate the efficacy of an injectable local anesthetic nanocomposite carrier to provide sustained analgesic effect. The nanocomposite carrier was developed by encapsulating ropivacaine, a local anesthetic, in lipid nanocapsules (LNC-Rop), and incorporating the nanocapsules in enzymatically crosslinked glycol chitosan (0.3GC) hydrogels. Cryo Scanning Electron Microscopic (Cryo SEM) images showed the ability to distribute the LNCs within the hydrogel without adversely affecting their morphology. The study demonstrated the feasibility to achieve sustained release of lipophilic molecules from the nanocomposite carrier in vitro and in vivo . A rat chronic constriction injury (CCI) pain model was used to evaluate the efficacy of the nanocomposite carrier using thermal paw withdrawal latency (TWL). The nanocomposite carriers loaded with ropivacaine and dexamethasone showed significant improvement in pain response compared to the control groups for at least 7 days. The study demonstrated the clinical potential of these nanocomposite carriers for post-operative and neuropathic pain. Statement of Significance Acute or chronic pain associated with musculoskeletal conditions is considered a major health issue, with healthcare costs totaling several billion dollars. The opioid crisis presents a pressing clinical need to develop alternative and effective approaches to treat musculoskeletal pain. The goal of this study was to develop a long-acting injectable anesthetic formulation which can sustain a local anesthetic effect for a prolonged time. This in turn could increase the quality of life and rehabilitation outcome of patients, and decrease opioid consumption. The developed injectable nanocomposite demonstrated the feasibility to achieve prolonged pain relief in a rat chronic constriction injury (CCI) model. [ABSTRACT FROM AUTHOR]

Voluntary resettlement, typically framed by the principle of free, prior, and informed consent (FPIC), has emerged as a preferred alternative to the heavily criticized forced resettlement approach, but there are growing concerns over whether those “voluntary” programs are genuinely voluntary. In China, the government maintains that its poverty alleviation resettlement (PAR) program is a successful example of voluntary resettlement. Under this national anti-poverty initiative, millions of people living in the poorest parts of the country have been resettled “voluntarily”. However, few studies have critically examined this claim. In this study, we collected empirical evidence through a survey of PAR resettlers. Drawing on a large and representative household survey (1723 resettlers from 30 different PAR projects) and 142 qualitative interviews, we report inconclusive and conflicting findings. On the one hand, the respondents strongly expressed that they willingly participated in resettlement. The perception of willingness was especially high among those who were younger, wealthier, and had off-farm employment. Furthermore, the consent to relocate was mostly free and driven by a desire to improve the quality of life. On the other hand, we observed that consent was not fully informed due to inadequate consultation. The villagers were not given detailed information about the resettlement or time to consider the implications. To ensure genuinely voluntary resettlement and to enhance the effectiveness of the program in poverty alleviation, the government needs to improve the consultation process, offer more targeted assistance to poor households, and provide better post-resettlement support. [ABSTRACT FROM AUTHOR]

Prostate cancer displays a wide spectrum of clinical behaviour from biological indolence to rapidly lethal disease, but we remain unable to accurately predict an individual tumor’s future clinical course at an early curable stage. Beyond basic dimensions and volume calculations, tumor morphometry is an area that has received little attention, as it requires the analysis of the prostate gland and tumor foci in three-dimensions. Previous efforts to generate three-dimensional prostate models have required specialised graphics units and focused on the spatial distribution of tumors for optimisation of biopsy strategies rather than to generate novel morphometric variables such as tumor surface area. Here, we aimed to develop a method of creating three-dimensional models of a prostate’s pathological state post radical prostatectomy that allowed the derivation of surface areas and volumes of both prostate and tumors, to assess the method’s accuracy to known clinical data, and to perform initial investigation into the utility of morphometric variables in prostate cancer prognostication. Serial histology slides from 21 prostatectomy specimens covering a range of tumor sizes and pathologies were digitised. Computer generated three-dimensional models of tumor and prostate space filling models were reconstructed from these scanned images using Rhinoceros 4.0 spatial reconstruction software. Analysis of three-dimensional modelled prostate volume correlated only moderately with weak concordance to that from the clinical data (r = 0.552, θ = 0.405), but tumor volume correlated well with strong concordance (r = 0.949, θ = 0.876). We divided the cohort of 21 patients into those with features of aggressive tumor versus those without and found that larger tumor surface area (32.7 vs 3.4cc, p = 0.008) and a lower tumor surface area to volume ratio (4.7 vs 15.4, p = 0.008) were associated with aggressive tumor biology. [ABSTRACT FROM AUTHOR]

Cardiac tamponade is often evaluated through echocardiography. However, not all patients with tamponade physiology develop clinical tamponade. Thus, we evaluated various echocardiographic and clinical factors as predictors of the need for intervention. Echocardiographic database was searched for reports containing the term "tamponade physiology" and 411 subjects identified. This preliminary report covers 88 subjects for whom we have complete data regarding pericardial intervention, readmissions, and inpatient mortality. We compared demographics, comorbidities, and clinical parameters of patients who received interventions vs conservative care. Factors with p value of <0.20 were included in a multivariable logistic regression model. Of the 88 subjects 42 (48%) had an intervention (37 had pericardiocentesis, 4 had pericardial window, 1 had both). Two patients required a second pericardiocentesis on re-hospitalization, and two died during the index hospitalization. Only 1 subject in the non-intervention group later required pericardiocentesis. Moderate-large effusion was more prevalent in the intervention group (p=0.017) as was IVC plethora (p=0.003); the prevalence of RV diastolic/RA systolic collapse and respiratory variation of Doppler flows was similar between groups. Looking at all echo parameters, the intervention group had median of 2 positive values (IQR 1-3) vs. 1.5 (IQR 1-2) in the conservative group (p=0.02). A multivariate model was created using demographic variables, etiology of effusion, and echo variables; area under the ROC curve for the model overall was 0.84 (95% CI [0.76-0.93]). In this initial sample approximately one-half of patients with tamponade physiology on echocardiography required intervention. A model using a combination of echo and demographic parameters demonstrated good but not perfect discrimination in predicting the need for intervention. Clinical judgment remains important. [ABSTRACT FROM AUTHOR]

• There is paucity of high-quality evidence for guideline directed medical therapy in the heart failure with reduced ejection fraction (HFrEF) population with chronic kidney disease. • Dialysis and kidney transplant recipients are underrepresented in HFrEF trials. • There is a need for wider inclusion of patients with advanced chronic kidney disease in randomized control trials in HFrEF. Patients with advanced chronic kidney disease (CKD) have largely been excluded from randomized control trials (RCTs) in heart failure (HF). This creates a paucity of high quality evidence for guideline directed medical therapy (GDMT), particularly in patients with heart failure with reduced ejection fraction (HFrEF) and CKD. This is a systematic review looking at the patterns and rates of inclusion of CKD in RCTs among patients with HFrEF. The search included RCTs from January 2010 to December 2020. A heat map was constructed to reflect the stages of CKD stages. The percentage of studies that included advanced CKD (stages IV-V) was recorded and log transformed, and then fitted into a time regression model. A P value of <0.05 was considered statistically significant. Out of the 3052 screened, 706 studies were included in the analysis. Only 61% of the RCTs reported at least some information on kidney function. There was a trend of increase in percentage of studies that included CKD stages IV-V from years 2010 to 2020. This was confirmed with a statistically significant linear trend P = 0.02 while the percentage of studies that included dialysis and kidney transplant recipients remained consistently low. There is a paucity of high-quality evidence for GDMT in the HFrEF population with CKD, particularly in those with advanced non-dialytic CKD, those on maintenance dialysis and kidney transplant recipients. There is a pressing need for wider inclusion of patients with advanced CKD in RCTs of GDMT in HFrEF. [ABSTRACT FROM AUTHOR]

Bone-targeted drug delivery is an active research area because successful clinical applications of this technology can significantly advance the treatment of bone injuries and disorders. Molecules with bone-targeting potential have been actively investigated as promising moieties in targeted drug delivery systems. In general, bone-targeting molecules are characterized by their high affinity for bone and their predisposition to persist in bone tissue for prolonged periods, while maintaining low systemic concentrations. Proteins, such as monoclonal antibodies, have shown promise as bone-targeting molecules; however, they suffer from several limitations including large molecular size, high production cost, and undesirable immune responses. A viable alternative associated with significantly less side effects is the use of small molecule-based targeting moieties. This review provides a summary of recent findings regarding small molecule compounds with bone-targeting capacity, as well as nanoscale targeted drug delivery approaches employing these molecules. [ABSTRACT FROM AUTHOR]

Rural electrification is a crucial process of enhancing the modern energy access of rural communities which is an important global development goal. Electric cooperatives have played an important role as drivers of rural electrification worldwide, both historically and contemporaneously. The emerging role of cooperatives in rural electrification is yet to be examined in the context of East Africa, a region that experiences serious infrastructure deficits alongside widespread rural poverty. This study adopts a political economy perspective to explore the roles and challenges of cooperatives in rural electrification in Uganda. Through a high-level case study of two electric cooperatives, we show that while the cooperatives can deliver rural electrification, they face a series of political and economic challenges in fulfilling their mission. To enhance rural electrification through cooperatives, the challenges should be addressed by policy solutions: (1) providing more support to rural households that cannot afford electricity; (2) providing further support to cooperatives to avoid overburdening the community; (3) enhancing investment to upgrade the grid and extend its geographical coverage; and (4) exploring new financial and technological options for rural electrification. We expect the findings of this study to be useful to policymakers, implementers, cooperatives, and international donors currently working in rural electrification in Africa and beyond. [ABSTRACT FROM AUTHOR]

Poverty alleviation resettlement (PAR) is one of China’s key poverty reduction initiatives. Through this state-led resettlement programme, the government aims to improve the living standards and access to infrastructure and services of the rural poor. This paper examines PAR from the perspective of spatial restructuring through a household survey conducted in Shanxi and Shaanxi provinces. A total of 30 resettlement sites were examined. The results show that PAR has two spatial forms: long-distance resettlement, which resettles people to cities or towns, and short-distance resettlement, which resettles people within the administrative boundaries of their village or to a nearby village. Furthermore, the type of spatial restructuring is an important factor shaping the outcome of resettlement. While long-distance resettlement outperforms short-distance resettlement in terms of gains in income, the advantage is offset by higher post-resettlement expenses. Furthermore, long-distance resettlers face a greater challenge in securing non-agricultural employment. Consequently, the level of satisfaction is lower among long-distance resettlers. Significant challenges remain to be addressed for both types of resettlement, including establishing two-way communication between villagers and the government about resettlement plans and providing better financial support for the resettlers, safeguards for the livelihoods of non-movers, and post-resettlement support programmes to help resettlers adjust to their new environments. [ABSTRACT FROM AUTHOR]

Environmental justice is a key concept for understanding the contested relationship between pastoralism and conservation. Our study adopted a political approach to examine conservation, pastoralism, and justice in the context of the grazing ban policy in China. Employing a qualitative, in-depth case study, we investigated the local political actors and processes that lead to environmental (in)justice. The evidence shows how injustice is perpetuated by both centralized and decentralized political processes and how herders use their knowledge and strategies in resistance to the injustice. In addition, the study contributed to a pluralistic understanding of justice by examining the different notions of justice held by the herders. We found that herders perceive injustices through different lenses, namely economic, ecological, and cultural aspects. Further, the similarities and differences between Han and Mongolian herders are discussed in terms of their notions of environmental justice and counteractions. [ABSTRACT FROM AUTHOR]

There are limited data on clinical outcomes in patients re-admitted with decompensated heart failure (HF) with concomitant liver cirrhosis. We conducted a cross sectional analysis of the Nationwide Readmissions Database (NRD) years 2010 thru 2012. An Index admission was defined as a hospitalization for decompensated heart failure among persons aged ≥ 18 years with an alive discharge status. The main outcome was 30 - day all-cause rehospitalization. Survey logistic regression provided the unadjusted and adjusted odds of 30 - day rehospitalization among persons with and without cirrhosis, accounting for age, gender, kidney dysfunction and other comorbidities. There were 2,147,363 heart failure (HF) hospitalizations among which 26,156 (1.2%) had comorbid cirrhosis. Patients with cirrhosis were more likely to have a diagnosis of acute kidney injury (AKI) during their index hospitalization (18.4% vs 15.2%). There were 469,111 (21.9%) patients with readmission within 30 - days. The adjusted odds of a 30 - day readmission was significantly higher among patients with cirrhosis compared to without after adjusting for comorbid conditions (adjusted Odds Ratio [aOR], 1.3; 95% Confidence Interval [CI}: 1.2 to 1.4). The relative risk of 30 - day readmission among those with cirrhosis but without renal disease (aOR, 1.3; 95% CI: 1.3 to 1.3) was lower than those with both cirrhosis and renal disease (aOR, 1.8; 95% CI: 1.6 to 2.0) when compared to persons without either comorbidities. Risk of 30 - day rehospitalization was significantly higher among patients with heart failure and underlying cirrhosis. Concurrent renal dysfunction among patients with cirrhosis hospitalized for decompensated HF was associated with a greater odds of rehospitalization. [ABSTRACT FROM AUTHOR]

The microgrid is a new concept in China and may potentially play an important role in enhancing the resilience and sustainability of electricity generation and distribution. However, the development of microgrids faces many challenges. This study examines the barriers to microgrid development using a case study of a pilot zone in Qingdao. Drawing on the theories of multi-level perspective and multi-actor perspective, we presented new empirical evidence on how the pilot microgrid projects were rendered difficult by the resistance from the existing industrial regime and the challenging economic and socio-political environments. The monopoly of state-owned grid operators in electricity transmission and distribution is difficult to break at a local level. The findings deepen our understanding of the challenges encountered by innovators in China's microgrid development and hold implications for policymakers in making more targeted policy mixes to support energy transition activities. [ABSTRACT FROM AUTHOR]

Lithium is widely used as a treatment of bipolar disorder, a neuropsychiatric disorder associated with disrupted circadian rhythms. Lithium is known to lengthen period and increase amplitude of circadian rhythms. One possible pathway for these effects involves inhibition of glycogen synthase kinase-3β (GSK-3β), which regulates degradation of CRY2, a canonical clock protein determining circadian period. CRY1 is also known to play important roles in regulating circadian period and phase, although there is no evidence that it is similarly phosphorylated by GSK-3β. In this paper, we tested the hypothesis that lithium affects circadian rhythms through CRYs. We cultured fibroblasts and slices of the suprachiasmatic nucleus (SCN), the master circadian pacemaker of the brain, from Cry1 -/-, Cry2 -/-, or wild-type (WT) mice bearing the PER2:LUC circadian reporter. Lithium was applied in the culture medium, and circadian rhythms of PER2 expression were measured. In WT and Cry2-/- fibroblasts, 10 mM lithium increased PER2 expression and rhythm amplitude but not period, and 1 mM lithium did not affect either period or amplitude. In non-rhythmic Cry1 -/- fibroblasts, 10 mM lithium increased PER2 expression. In SCN slices, 1 mM lithium lengthened period ∼1 h in all genotypes, but did not affect amplitude except in Cry2-/- SCN. Thus, the amplitude-enhancing effect of lithium in WT fibroblasts was unaffected by Cry2 knockout and occurred in the absence of period-lengthening, whereas the period-lengthening effect of lithium in WT SCN was unaffected by Cry1 or Cry2 knockout and occurred in the absence of rhythm amplification, suggesting that these two effects of lithium on circadian rhythms are independent of CRYs and of each other. [ABSTRACT FROM AUTHOR]

This paper challenges the prevailing perception that the environmental governance of China is a case exemplar of authoritarian environmentalism. Using low-carbon governance as an example, it shows that although China's national low-carbon policy appears highly authoritarian, the situation on the ground is much more ambiguous, displaying a mixture of authoritarian and liberal features. While China's top-down and non-participatory policy environment has been crucial in stimulating a low-carbon transition, the failure of the central government to control local actors has created a situation of de facto neoliberal environmentalism, where local governments and energy-intensive enterprises enjoy a high degree of freedom and flexibility to manage their own energy consumption in spite of the overt authoritarian rule. The findings of this research show that viewing China's environmental governance as a clear-cut instance of authoritarian environmentalism should be done with circumspection, and that studying the nature of environmental governance as a complex process requires a thorough understanding of not just national policy but also local politics and the ways the two are connected. [ABSTRACT FROM AUTHOR]

The Ten-Thousand Enterprises Program is China’s keystone energy conservation and climate change program. The program has effectively created a class of energy-intensive enterprises that are regulated by the government for energy conservation purposes. Through an empirical study conducted in Changchun, this paper shows that the adoption of energy efficiency technologies and practices has been highly uneven in this class of enterprises because of two reasons. First, a de facto two-tier regulatory system has emerged within the framework of the Ten-Thousand Enterprises Program. Central state-owned enterprises are closely regulated by the State-Owned Assets Supervision and Administration Commission (SASAC) which is a central government apparatus, whereas local state-owned enterprises and privately owned enterprises are regulated by the local government, which has fewer resources and incentives to implement the program rigorously. Second, the Ten-Thousand Enterprises Program bundles together different types of enterprises. This approach places smaller enterprises at a disadvantage and limits their ability to conserve energy. [ABSTRACT FROM AUTHOR]

Urban expansion is a controversial process where territorial conflicts of differing interests and objectives become manifest. The existing interpretations of urban expansion pay insufficient attention to the strategies deployed by municipal governments to resolve the territorial conflicts arising out of urban expansion. This paper identifies two key bargaining arenas through which municipal governments mitigate the territorial complications of urban expansion. First, administrative annexation not only involves municipal governments to gain control over more territory, but also entails strategies adopted to reconcile conflicts created by administrative restructuration, such as offering preferential fiscal and job arrangements. Second, land acquisition is not only about livelihood restoration of landless farmers but is also about converting them into citizens constituting new urban communities and integrating them into the urban mode of production. These bargaining arenas are the sites where the benefits and concessions of urban expansion are negotiated, and they play a key role in ensuring the smooth operation of urban expansion by resolving potential conflicts among stakeholders. • Territorial conflicts are common in urban expansion projects. • Territorial conflicts arising from administrative annexation and land acquisition • Territorial conflicts can be resolved through bargaining and compromises. [ABSTRACT FROM AUTHOR]

Rumors are an important yet poorly understood dynamic in environmental politics, particularly regarding their role in environmental activism. Drawing on theories of rumors, environmental information governance, and environmental activism, we analyzed the eco-politics of rumors in a Chinese village that experienced rumor-fueled protests against the construction and operation of a limestone quarry. We make three arguments regarding the condition, control, and content of rumors. First, poor environmental information governance, driven by a development-first and prejudice-rich official narrative and the strategic behaviors of blame and accountability avoidance, provides an important condition for rumor formulation and circulation. Second, the generation and circulation of rumors can be understood as a collective sense-making process driven by the informal communication between external and internal sources of information. The ephemeral nature of communication and group sanctions on government supporters make it difficult for authorities to control rumors. Third, by conceptualizing rumors as information warfare against official narratives, we show that rumors can foster a sense of collective urgency, reframe a land-right protest into an environmental protest that is politically more likely to succeed, and undermine public trust in local authorities. The findings suggest that rumors are an important part of environmental politics in China because of their role in environmental activism. [ABSTRACT FROM AUTHOR]

Musculoskeletal regenerative engineering approach using small bioactive molecules in conjunction with advanced materials has emerged as a highly promising strategy for musculoskeletal repair and regeneration. Advanced biomaterials technologies have revealed nanofiber-based scaffolds for musculoskeletal tissue engineering as vehicles for the controlled delivery of small molecule drugs. This review article highlights recent advances in nanofiber-based delivery of small molecules for musculoskeletal regenerative engineering. The article concludes with perspectives on the challenges and future directions. From the Clinical Editor In this review, advances in nanofiber-based delivery of small molecules are discussed from the standpoint of their potential role in musculoskeletal regenerative engineering, highlighting both future directions and current challenges. [ABSTRACT FROM AUTHOR]

State-owned forestry enterprises (SOFEs) in China, established during the Maoist era for forest exploitation, have undergone significant reorganization under the Natural Forest Conservation Program (NFCP). In this study, drawing on the perspectives of political ecology and a case study from a SOFE in the Greater Khingan Range in northeast China, we develop an eco-socialist perspective to understand this particular approach to forest conservation. The concept of eco-socialism is mobilized to describe how, as a form of all-encompassing social organization with overwhelming political, social, and economic power in the forestry regions, the eco-restructuring of SOFEs is key to the success of forest conservation. Four eco-restructuring processes have been identified: (1) declining timber sales and increasing central subsidies; (2) restructuring of work-units; (3) creating redundancies; and (4) developing new sustainable economic activities. Furthermore, these eco-restructuring processes, both mandated and supported by the central government, have a significant impact on state-society relationship. While the resources given by the central government allow SOFEs to maintain a stable relationship with some workers by providing them a relatively stable livelihood, the laid-off workers are the major victims of the process, as they suffer from loss of income, economic stability, and social self-esteem. This study enriches the literature by incorporating eco-socialist governmentality into the political ecology of forest conservation and illustrating how the political ecology perspective can be a powerful tool in the collective effort to craft sustainable and socially just futures in China. [ABSTRACT FROM AUTHOR]

Abstract: The Chinese government has promulgated a wide variety of low-carbon initiatives to control the rapid growth of energy consumption and carbon emissions in the cities. Past records, however, show that the central government's policies are often poorly implemented or distorted by local officials. Using a case study from the city of Changchun, this paper examines how and why the issue of poor implementation persists despite the establishment of the Energy Conservation Target Responsibility System (ECTRS). As a key institutional mechanism providing local officials with political incentives to implement low-carbon policies, the ECTRS has been constrained by a number of problems, including a poorly designed scoring system, weak targets, the use of energy intensity instead of absolute energy consumption as a policy objective, and the lack of reliable local energy statistics. [Copyright &y& Elsevier]

Highlights: [•] Regenerative engineering has been recently proposed to regenerate complex tissue. [•] Therapeutic proteins have many limitations for their use in regenerating tissues. [•] Small-molecule-based therapeutics is emerging as an alternative strategy. [•] Small molecules may represent the next generation in musculoskeletal regenerative medicine. [ABSTRACT FROM AUTHOR]

Abstract: Renewable energy and energy efficiency (REEE) policies have far-reaching implications for energy security, climate change, economic competitiveness, pollution, and human livelihood. For these reasons, REEE has become a national priority for the Chinese government, particularly since 2005. This paper aims to critically review China's REEE policies in six sectors: electricity, industry, transportation, buildings, and local government. In addition to examining the progress China has made in the development and implementation of REEE policies, this review also identifies limitations and room for improvement. Finally, five policy recommendations are presented. [Copyright &y& Elsevier]

Abstract: The release of the Twelfth Five-Year Guideline for National Economic and Social Development in March 2011 marked the beginning of China’s Twelfth Five-Year Plan (12th FYP) period (2011–2015). Energy conservation continues to be a national priority. Since the release, new energy conservation policies and programs have been announced by many central ministries in accordance with the 12th FYP. Is this the beginning of a new paradigm or merely a continuation of the 11th FYP model? This paper describes and analyzes key changes in energy conservation since 2011, including a more conservative national energy conservation target, a more logical way of breaking down the target, new sectoral targets, the introduction of new programs, and the expansion of existing programs. However, one key problem of the 11th FYP period remains unresolved, namely the inability to shift the economy away from heavy industry. [Copyright &y& Elsevier]

Abstract: The emergence of gated communities for foreign residents in large Chinese cities is the result of economic globalisation, local institutional changes, social relations and cultural globalisation. Using a case study performed in Beijing, this paper seeks to analyse the complex dynamics of foreign gated communities through a critical examination of their key actors. The history of the gated community studied here is divided into two phases: development and localisation. During the development phase, the property developer not only attracted foreign residents through building an international community but also lured Hong Kong investors through the promise of soaring rental returns fuelled by strong demand. During the localisation phase, Chinese residents gradually replaced the developer as the project’s key actors. While the Chinese residents were attracted by the idea of international community, their arrival significantly transformed the community. This paper demonstrates how the survival, character and appearance of a foreign gated community was influenced by temporally and geographically dispersed actors who were subjected to a number of economic, social and cultural forces on a global and a local scale. [Copyright &y& Elsevier]

The optimization of rural land-use through land consolidation has become an indispensable part of reform in China, significantly impacting rural settlements and their residents. Given the growing social problems due to land consolidation, this study proposes a new land consolidation approach that involves helping rural residents relocate from small settlements to vacant properties in large settlements through a homestead exchange mechanism. We argue that this targeted approach can achieve land-use optimization, without the negative impacts of the conventional approach to land consolidation. To evaluate our idea empirically, we conducted a case study in Jilin Province. The simulation estimated that our approach could increase the effective amount of arable land by 1046.66 km2 and the average size of rural settlements by 51.9%, while decreasing the number of rural settlements by 44.6%. Therefore, our approach can achieve the objective of land-use optimization, despite the highly complex context and varying degrees of rural fragmentation and hollowing. • Land consolidation is an important policy to achieve rural land-use optimization. • A new approach to land consolidation that is less disruptive is proposed. • The approach is based on a voluntary homestead exchange mechanism. • Assist rural residents to relocate from small settlements to large settlements. • Simulation shows that approach can achieve the objective of land-use optimization. [ABSTRACT FROM AUTHOR]