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Importance Hypertension and albuminuria are markers of diabetes-related nephropathy and important factors associated with kidney outcomes in pediatric type 2 diabetes. However, their prevalence in these patients is unknown. Objective To measure the prevalence of hypertension and albuminuria in pediatric patients with type 2 diabetes and to evaluate the association of sex and race/ethnicity with these conditions. Data sources MEDLINE, Embase, CINAHL, Cochrane Library, Web of Science, the gray literature, and references of the screened articles were searched for human studies from date of database inception to February 20, 2020. Study selection Observational studies with at least 10 participants reporting the prevalence of hypertension and/or albuminuria in pediatric patients with type 2 diabetes were included. Three teams of 2 independent reviewers screened 7614 papers, of which 60 fulfilled the eligibility criteria. Data extraction and synthesis Three teams of 2 independent reviewers performed data extraction, risk of bias analysis, and level of evidence analyses. The meta-analysis was conducted using a random-effects model and followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Main outcomes and measures The primary outcomes included the pooled prevalence rates (percentages with 95% CI) for hypertension and albuminuria. The secondary outcomes assessed pooled prevalence rates by sex and racial/ethnic group. Results Sixty studies were included in the systematic review. Diabetes duration varied from inclusion at diagnosis to 15.0 years after diagnosis, and the reported mean age at diagnosis ranged from 6.5 to 21.0 years. Hypertension prevalence among 3463 participants was 25.33% (95% CI, 19.57%-31.53%). Male participants had higher hypertension risk than female participants (odds ratio [OR], 1.42 [95% CI, 1.10-1.83]), with Pacific Islander and Indigenous youth having the highest prevalence of all racial/ethnic groups (Pacific Islander youth: 26.71% [95% CI, 14.54%-40.72%]; Indigenous youth: 26.48% [95% CI, 17.34%-36.74%]; White youth: 20.95% [95% CI, 12.65%-30.57%]; African American youth: 19.04% [95% CI, 12.01%-27.23%]; Hispanic/Latino youth: 15.11% [95% CI, 6.56%-26.30%]; Asian youth: 18.37% [95% CI, 9.49%-29.23%]). Albuminuria prevalence among 2250 participants was 22.17% (95% CI, 17.34%-27.38%). Pacific Islander youth, Indigenous youth, and Asian youth had higher prevalence rates than White youth (Pacific Islander youth: 31.84% [95% CI, 11.90%-55.47%]; Indigenous youth: 24.27% [95% CI, 14.39%-35.73%]; Asian youth: 23.00% [95% CI, 18.85%-27.41%]; White youth: 12.59% [95% CI, 7.75%-18.33%]), with no sex differences (OR for male vs female participants, 0.68 [95% CI, 0.46-1.01]). Heterogeneity was high among studies, with a low to moderate risk of bias. Conclusions and relevance In this study, markers of diabetes-related nephropathy were commonly detected in pediatric patients with type 2 diabetes, with a disproportionate burden noted among Pacific Islander and Indigenous youth. Personalized management strategies to target kidney outcomes are urgently needed in pediatric patients with type 2 diabetes to alleviate the burden of this condition on the kidneys.

BACKGROUND Brain metastases (BM) are prevalent in several primary cancers and are the most commonly diagnosed intracranial tumours in adults. The aim of this systematic review was to critically evaluate and compare existing management paradigms for BMs from all primary tumour sites. METHODS We searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, and CENTRAL for randomized controlled trials (RCTs) published until October 2018 and selected comparative RCTS with >50 patients. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). RESULTS A screen of 3188 abstracts yielded 49 RCTs with 8122 patients. The median sample size was 103 (range 39–779). 17/49 RCTs included lung cancer patients, 3/49 breast cancer, 2/49 melanoma, and 27/49 all primary tumour sites. Most studies were phase II/III superiority, open-label, parallel trials. All included patients >18 years of age with at least 1 BM proven on CT/MRI. Most included patients with favorable performance status (KPS >70 or ECOG 0–2). Interventions compared included targeted therapies (e.g. EGFR inhibitors, 7/49), chemotherapeutic regimens (28/49), WBRT (43/49), SRS (12/49), and surgical resection (3/49). A statistically significant difference in OS was reported by 7 studies, and in PFS by 8 studies. Of these, 3 showed improved PFS or OS on addition of temozolomide to WBRT, and 2 showed improved PFS in EGFR-positive patients treated with EGFR inhibitors. The incidence of serious adverse events was not substantially different between treatment arms in most studies. CONCLUSIONS Though the majority of studies did not report a benefit to OS or PFS, temozolomide + WBRT showed a benefit in 3 studies, and improvement in PFS was seen in EGFR-positive patients treated with EGFRi. Given the varying treatment approaches in practice today, these data support the need for a meta-analysis to accurately characterize the efficacy of existing treatment options for specific patient populations.

A result of great theoretical and experimental interest, Jarzynski equality predicts a free energy change $\Delta F$ of a system at inverse temperature $\beta$ from an ensemble average of non-equilibrium exponential work, i.e., $\langle e^{-\beta W}\rangle =e^{-\beta\Delta F}$. The number of experimental work values needed to reach a given accuracy of $\Delta F$ is determined by the variance of $e^{-\beta W}$, denoted ${\rm var}(e^{-\beta W})$. We discover in this work that ${\rm var}(e^{-\beta W})$ in both harmonic and an-harmonic Hamiltonian systems can systematically diverge in non-adiabatic work protocols, even when the adiabatic protocols do not suffer from such divergence. This divergence may be regarded as a type of dynamically induced phase transition in work fluctuations. For a quantum harmonic oscillator with time-dependent trapping frequency as a working example, any non-adiabatic work protocol is found to yield a diverging ${\rm var}(e^{-\beta W})$ at sufficiently low temperatures, markedly different from the classical behavior. The divergence of ${\rm var}(e^{-\beta W})$ indicates the too-far-from-equilibrium nature of a non-adiabatic work protocol and makes it compulsory to apply designed control fields to suppress the quantum work fluctuations in order to test Jarzynski equality., Comment: 14 pages, 9 figures. revised version (fixing a minor issue in some equation numbers in v2)

Work is one of the most basic notion in statistical mechanics, with work fluctuation theorems being one central topic in nanoscale thermodynamics. With Hamiltonian chaos commonly thought to provide a foundation for classical statistical mechanics, here we present general salient results regarding how (classical) Hamiltonian chaos generically impacts on nonequilibrium work fluctuations. For isolated chaotic systems prepared with a microcanonical distribution, work fluctuations are minimized and vanish altogether in adiabatic work protocols. For isolated chaotic systems prepared at an initial canonical distribution at inverse temperature $\beta$, work fluctuations depicted by the variance of $e^{-\beta W}$ are also minimized by adiabatic work protocols. This general result indicates that if the variance of $e^{-\beta W}$ diverges for an adiabatic work protocol, then it diverges for all nonadiabatic work protocols sharing the same initial and final Hamiltonians. How such divergence explicitly impacts on the efficiency of using the Jarzynski's equality to simulate free energy differences is studied in a Sinai model. Our general insights shall boost studies in nanoscale thermodynamics and are of fundamental importance in designing useful work protocols., Comment: 11 pages, 5 figures, close to published version

Under a general framework, shortcuts to adiabatic processes are shown to be possible in classical systems. We then study the distribution function of the work done on a small system initially prepared at thermal equilibrium. It is found that the work fluctuations can be significantly reduced via shortcuts to adiabatic processes. For example, in the classical case probabilities of having very large or almost zero work values are suppressed. In the quantum case negative work may be totally removed from the otherwise non-positive-definite work values. We also apply our findings to a micro Otto-cycle-based heat engine. It is shown that the use of shortcuts, which directly enhances the engine output power, can also increase the heat engine efficiency substantially, in both quantum and classical regimes., 8 pages, 4 figures, finalized version published in the December 2013 issue of Phys. Rev. E