Real-time jitter correction in a photonic analog-to-digital converter.

A real-time jitter meter is used to measure and digitally sample the pulse-to-pulse timing error in a laser pulse train. The jitter meter is self-referenced using a single-pulse delay line interferometer and measures timing jitter using optical heterodyne detection between two frequency channels of the pulse train. Jitter sensitivity down to 3×10-10fs2/Hz at 500 MHz has been demonstrated with a pulse-to-pulse noise floor of 1.6 fs. As a proof of principle, the digital correction of the output of a high-frequency photonic analog-to-digital converter (PADC) is demonstrated with an emulated jitter signal. Up to 23 dB of jitter correction, down to the noise floor of the PADC, is accomplished with radio-frequency modulation up to 40 GHz.

Intradialytic hypotension, blood pressure changes and mortality risk in incident hemodialysis patients.

Background: Intradialytic hypotension (IDH) occurs frequently in maintenance hemodialysis (HD) patients and may be associated with higher mortality. We hypothesize that nadir intradialytic systolic blood pressure (niSBP) is inversely related to death risk while iSBP change (Δ) and IDH frequency are incrementally associated with all-cause mortality. Methods: In a US-based cohort of 112 013 incident HD patients over a 5-year period (2007-11), using niSBP, ΔiSBP (pre-HD SBP minus niSBP) and IDH frequency (proportion of HD treatments with niSBP <90 mmHg) within the first 91 days of HD, we examined mortality-predictability at 1, 2 and 5 years using Cox models and restricted cubic splines adjusted for case-mix, comorbidities and laboratory covariates. Results: We observed that niSBP of <90 and ≥140 mmHg had a 5-year mortality hazard ratio (HR) (95% confidence interval) of 1.57 (1.47-1.67) and 1.25 (1.18-1.33), respectively, compared with niSBP 110 to <120 mmHg. ΔiSBP of <15 and ≥50 compared with 21-30 mmHg had mortality HR of 1.31 (1.26-1.37) and 1.32 (1.24-1.39), respectively. Among patients with >40% IDH frequency, we observed a mortality HR of 1.49 (1.42-1.57) compared with 0% IDH frequency in fully adjusted models. These associations were robust at 1 and 2 years of follow-up. Conclusion: In conclusion, we observed a U-shaped association between niSBP and ΔiSBP and mortality and a direct linear relationship between IDH frequency and mortality. Our findings lend some prognostic insight of HD blood pressure and hemodynamics, and have the potential to guide blood pressure management strategies among the HD population.

Incremental dialysis for preserving residual kidney function-Does one size fit all when initiating dialysis?

While many patients have substantial residual kidney function (RKF) when initiating hemodialysis (HD), most patients with end stage renal disease in the United States are initiated on 3-times per week conventional HD regimen, with little regard to RKF or patient preference. RKF is associated with many benefits including survival, volume control, solute clearance, and reduced inflammation. Several strategies have been recommended to preserve RKF after HD initiation, including an incremental approach to HD initiation. Incremental HD prescriptions are personalized to achieve adequate volume control and solute clearance with consideration to a patient's endogenous renal function. This allows the initial use of less frequent and/or shorter HD treatment sessions. Regular measurement of RKF is important because HD frequency needs to be increased as RKF inevitably declines. We narratively review the results of 12 observational cohort studies of twice-weekly compared to thrice-weekly HD. Incremental HD is associated with several benefits including preservation of RKF as well as extending the event-free life of arteriovenous fistulas and grafts. Patient survival and quality of life, however, has been variably associated with incremental HD. Serious risks must also be considered, including increased hospitalization and mortality perhaps related to fluid and electrolyte shifts after a long interdialytic interval. On the basis of the above literature review, and our clinical experience, we suggest patient characteristics which may predict favorable outcomes with an incremental approach to HD. These include substantial RKF, adequate volume control, lack of significant anemia/electrolyte imbalance, satisfactory health-related quality of life, low comorbid disease burden, and good nutritional status without evidence of hypercatabolism. Clinicians should engage patients in on-going conversations to prepare for incremental HD initiation and to ensure a smooth transition to thrice-weekly HD when needed.

There's no place like home: 35-year patient survival on home hemodialysis.

The vast majority of maintenance dialysis patients suffer from poor long-term survival rates and lower levels of health-related quality of life. However, home hemodialysis is a historically significant dialysis modality that has been associated with favorable outcomes as well as greater patient autonomy and control, yet only represents a small minority of the total dialysis performed in the United States. Some potential disadvantages of home hemodialysis include vascular access complications, infection-related hospitalizations, patient fatigue, and attrition. In addition, current barriers and challenges in expanding the utilization of this modality include limited patient and provider education and technical expertise. Here we report a 65-year old male with end-stage renal disease due to Alport's syndrome who has undergone 35 years of uninterrupted thrice-weekly home hemodialysis (ie, every Sunday, Tuesday, and Thursday evening, each session lasting 3 to 3» hours in length) using a conventional hemodialysis machine who has maintained a high functional status allowing him to work 6-8 hours per day. The patient has been able to liberalize his dietary and fluid intake while only requiring 3-4 liters of ultrafiltration per treatment, despite having absence of residual kidney function. Through this case of extraordinary longevity and outcomes after 35 years of dialysis and a review of the literature, we illustrate the history of home hemodialysis, its significant clinical and psychosocial advantages, as well as the barriers that hinder its widespread adaptation.

Racial and Ethnic Differences in Mortality Associated with Serum Potassium in a Large Hemodialysis Cohort.

BACKGROUND: Hyperkalemia is observed in chronic kidney disease patients and may be a risk factor for life-threatening arrhythmias and death. Race/ethnicity may be important modifiers of the potassium-mortality relationship in maintenance hemodialysis (MHD) patients given that potassium intake and excretion vary among minorities. METHODS: We examined racial/ethnic differences in baseline serum potassium levels and all-cause and cardiovascular mortality using Cox proportional hazard models and restricted cubic splines in a cohort of 102,241 incident MHD patients. Serum potassium was categorized into 6 groups: ≤3.6, >3.6 to ≤4.0, >4.0 to ≤4.5 (reference), >4.5 to ≤5.0, >5.0 to ≤5.5, and >5.5 mEq/L. Models were adjusted for case-mix and malnutrition-inflammation cachexia syndrome (MICS) covariates. RESULTS: The cohort was composed of 50% whites, 34% African-Americans, and 16% Hispanics. Hispanics tended to have the highest baseline serum potassium levels (mean ± SD: 4.58 ± 0.55 mEq/L). Patients in our cohort were followed for a median of 1.3 years (interquartile range 0.6-2.5). In our cohort, associations between higher potassium (>5.5 mEq/L) and higher mortality risk were observed in African-American and whites, but not Hispanic patients in models adjusted for case-mix and MICS covariates. While in Hispanics only, lower serum potassium (<3.6 mEq/L) levels were associated with higher mortality risk. Similar trends were observed for cardiovascular mortality. CONCLUSIONS: Higher potassium levels were associated with higher mortality risk in white and African-American MHD patients, whereas lower potassium levels were associated with higher death risk in Hispanics. Further studies are needed to determine the underlying mechanisms for the differential association between potassium and mortality across race/ethnicity.

Association of body weight changes with mortality in incident hemodialysis patients.

BACKGROUND: Incident hemodialysis patients may experience rapid weight loss in the first few months of starting dialysis. However, trends in weight changes over time and their associations with survival have not yet been characterized in this population. METHODS: In a large contemporary US cohort of 58 106 patients who initiated hemodialysis during 1 January 2007-31 December 2011 and survived the first year of dialysis, we observed trends in weight changes during the first year of treatment and then examined the association of post-dialysis weight changes with all-cause mortality. RESULTS: Patients' post-dialysis weights rapidly decreased and reached a nadir at the 5th month of dialysis with an average decline of 2% from baseline, whereas obese patients (body mass index ≥30 kg/m 2 ) did not reach a nadir and lost ∼3.8% of their weight by the 12th month. Compared with the reference group (-2 to 2% changes in weight), the death hazard ratios (HRs) of patients with -6 to -2% and greater than or equal to -6% weight loss during the first 5 months were 1.08 (95% confidence interval, 1.02-1.14) and 1.14 (1.07-1.22), respectively. Moreover, the death HRs with 2-6% and ≥6% weight gain during the 5th to 12th months were 0.91 (0.85-0.97) and 0.92 (0.86-0.99), respectively. CONCLUSIONS: In patients who survive the first year of hemodialysis, a decline in post-dialysis weight is observed and reaches a nadir at the 5th month. An incrementally larger weight loss during the first 12 months is associated with higher death risk, whereas weight gain is associated with greater survival during the 5th to 12th month but not in the first 5 months of dialysis therapy.

A brief review of intradialytic hypotension with a focus on survival.

Intradialytic hypotension (IDH), a common complication of ultrafiltration during hemodialysis therapy, is associated with high mortality and morbidity. IDH, defined as a nadir systolic blood pressure of less than 90 mm Hg on more than 30% of treatments, is a relevant definition and is correlated with mortality. Risk factors for IDH include patient demographics, anti-hypertensive medication use, larger interdialytic weight gain, and dialysis prescription features as dialysate sodium, high ultrafiltration rate, and dialysate temperature. A high frequency of IDH events carries a substantial death risk. An ultrafiltration rate >10 mL/h/kg, and even more so >13 mL/h/kg, is highly predictive of cardiovascular and all-cause mortality. Evidence suggests that IDH causes acute reversible segmental myocardial hypoperfusion and contractile dysfunction (myocardial stunning), which can result in long-term loss of myocardial contractility, leading to premature death. IDH also has negative end-organ effects on the brain and gut, contributing to mortality through stroke, and endotoxin translocation with associated inflammation and protein-energy wasting. Given strong association of IDH and dialysis mortality, a paradigm shift to its approach is urgently needed. Randomized controlled trials are required to prospectively test drugs and monitoring devices which may reduce IDH.

Incremental Hemodialysis: The University of California Irvine Experience.

Incremental hemodialysis has been examined as a viable hemodialysis regimen for selected end-stage renal disease (ESRD) patients. Preservation of residual kidney function (RKF) has been the driving impetus for this approach given its benefits upon the survival and quality of life of dialysis patients. While clinical practice guidelines recommend an incremental start of dialysis in peritoneal dialysis patients with substantial RKF, there remains little guidance with respect to incremental hemodialysis as an initial renal replacement therapy regimen. Indeed, several large population-based studies suggest that incremental twice-weekly vs. conventional thrice-weekly hemodialysis has favorable impact upon RKF trajectory and survival among patients with adequate renal urea clearance and/or urine output. In this report, we describe a case series of 13 ambulatory incident ESRD patients enrolled in a university-based center's Incremental Hemodialysis Program over the period of January 2015 to August 2016 and followed through December 2016. Among five patients who maintained a twice-weekly hemodialysis schedule vs. eight patients who transitioned to thrice-weekly hemodialysis, we describe and compare patients' longitudinal case-mix, laboratory, and dialysis treatment characteristics over time. The University of California Irvine Experience is the first systemically examined twice-weekly hemodialysis practice in North America. While future studies are needed to refine the optimal approaches and the ideal patient population for implementation of incremental hemodialysis, our case-series serves as a first report of this innovative management strategy among incident ESRD patients with substantial RKF, and a template for implementation of this regimen.

Volume Balance and Intradialytic Ultrafiltration Rate in the Hemodialysis Patient.

PURPOSE OF REVIEW: Volume management in hemodialysis patients is often challenging. Assessing volume status and deciding how much fluid to remove during hemodialysis, the so-called ultrafiltration rate (UFR), has remained a conundrum. RECENT FINDINGS: To date there is no objective assessment tool to determine the needed UFR during each hemodialysis session. Higher volume overload or higher UFR is associated with poor outcomes including worse mortality and unfavorable clinical outcomes. We suggest combined use of the following criteria to determine UFR or post-dialysis target dry weight: pre-hemodialysis blood pressure and its intradialytic changes, muscle cramps, dyspnea from pulmonary vascular congestion, peripheral edema, tachycardia or palpitation, headache or lightheadedness, perspiration, and post-dialysis fatigue. Restricting fluid and salt intake-and high-dose loop diuretic use in cases of residual kidney function-can be helpful in controlling fluid gains. More frequent and more severe hypotensive episodes are associated with poor outcomes including higher death risk.

North American experience with Low protein diet for Non-dialysis-dependent chronic kidney disease.

Whereas in many parts of the world a low protein diet (LPD, 0.6-0.8 g/kg/day) is routinely prescribed for the management of patients with non-dialysis-dependent chronic kidney disease (CKD), this practice is infrequent in North America. The historical underpinnings related to LPD in the USA including the non-conclusive results of the Modification of Diet in Renal Disease Study may have played a role. Overall trends to initiate dialysis earlier in the course of CKD in the US allowed less time for LPD prescription. The usual dietary intake in the US includes high dietary protein content, which is in sharp contradistinction to that of a LPD. The fear of engendering or worsening protein-energy wasting may be an important handicap as suggested by a pilot survey of US nephrologists; nevertheless, there is also potential interest and enthusiasm in gaining further insight regarding LPD's utility in both research and in practice. Racial/ethnic disparities in the US and patients' adherence are additional challenges. Adherence should be monitored by well-trained dietitians by means of both dietary assessment techniques and 24-h urine collections to estimate dietary protein intake using urinary urea nitrogen (UUN). While keto-analogues are not currently available in the USA, there are other oral nutritional supplements for the provision of high-biologic-value proteins along with dietary energy intake of 30-35 Cal/kg/day available. Different treatment strategies related to dietary intake may help circumvent the protein- energy wasting apprehension and offer novel conservative approaches for CKD management in North America.

Post-thoracotomy pain in children and adolescence: a retrospective cross-sectional study.

OBJECTIVE: We sought to determine the prevalence of chronic post-thoracotomy pain, defined as persistent or recurring incisional pain for at least 2 months after thoracotomy, in children. DESIGN: Retrospective cross-sectional study. SETTING: Quaternary pediatric teaching hospital. SUBJECTS: Patients who underwent a lateral thoracotomy from January 2005 to December 2007 at the Royal Children's Hospital, Melbourne, Australia. METHODS: Eligible patients were sent a questionnaire for telephonic completion with a researcher, with assistance from the parents if required. RESULTS: Of the 87 patients eligible to participate, 51 (59%) completed questionnaires. The majority of respondents was male (65%), underwent a single thoracotomy (84%; range 1-3), and were non-elective operations (71%). The median age at first thoracotomy was 5.7 (interquartile range [IQR] 2-14.2) years. The median age at questionnaire completion was 9.0 (IQR 5.4-17.9) years, with 3.6 (IQR 2.8-4.1) years between thoracotomy and time of questionnaire completion. Three patients (6%) scored ≥12 on self-report versions of the Leeds Assessment of Neuropathic Symptoms and Signs pain scale. Of these, only one patient complained of current post-thoracotomy pain. All three patients had a single thoracotomy and were older (mean age 14.2 years) at the time of thoracotomy. The rate of post-thoracotomy pain calculated using the binomial exact method is 1.96% (95% confidence interval 0-10.4%). CONCLUSIONS: Our study reports a low prevalence of post-thoracotomy pain in childhood and adolescence, and stands in contrast to previously published adult data.

A scoping review to map the research on the mental health of students and graduates during their university-to-work transitions.

OBJECTIVES: This scoping review maps the extant literature on students' and graduates' mental health experiences throughout their university-to-work transitions. The current review investigates the methodological features of the studies, the main findings, and the theories that the studies draw on to conceptualise mental health and transitions. DESIGN: This project used a scoping review methodology created and developed by Peters and colleagues and the Joanna Briggs Institute. The review searched academic databases and screened existing studies that met predetermined inclusion criteria. DATA SOURCES: Seven academic databases and Google Scholar were searched with sets of search terms. ELIGIBILITY: The included studies examined participants who were final-year university students or those who had graduated from university within a 3-year period. Studies published in English since 2000 and from any country were included. The review included studies examining the negative dimensions of mental health. The review excluded studies focusing on medical students and graduates. DATA EXTRACTION: Basic information about the studies and their findings on mental health and university-to-work transitions was retrieved. The findings are presented in tables and in a qualitative thematic summary. RESULTS: The scoping review included 12 studies. Mental health was often not explicitly defined and it's theoretical foundations were not clearly articulated. The review identified factors, including a lack of social support and economic precarity, as sources of adverse mental health. Other protective factors in these studies-variables that guard against mental health problems-were identified, such as career preparedness and having a good job. CONCLUSIONS: Despite the methodological focus on the negative aspects of mental health, people's mental health experiences during university-to-work transitions are not uniformly negative. Clear conceptualisations of mental health in future studies will aid in developing resources to improve well-being. TRIAL REGISTRATION NUMBER: This scoping review adhered to a protocol previously published in this journal and that is registered on the Open Science Framework website (https://osf.io/gw86x).

Giant tunable optical dispersion using chromo-modal excitation of a multimode waveguide.

The ability to control chromatic dispersion is paramount in applications where the optical pulsewidth is critical, such as chirped pulse amplification and fiber optic communications. Typically, devices used to generate large amounts (>100 ps/nm) of chromatic dispersion are based on diffraction gratings, chirped fiber Bragg gratings, or dispersion compensating fiber. Unfortunately, these dispersive elements suffer from one or more of the following restrictions: (i) limited operational bandwidth, (ii) limited total dispersion, (iii) low peak power handling, or (iv) large spatial footprint. Here, we introduce a new type of tunable dispersive device, which overcomes these limitations by leveraging the large modal dispersion of a multimode waveguide in combination with the angular dispersion of diffraction gratings to create chromatic dispersion. We characterize the device's dispersion, and demonstrate its ability to stretch a sub-picosecond optical pulse to nearly 2 nanoseconds in 20 meters of multimode optical fiber. Using this device, we also demonstrate single-shot, time-wavelength atomic absorption spectroscopy at a repetition rate of 90.8 MHz.

Dialysis Prescription and Sudden Death.

In the United States, end-stage renal disease patients receiving hemodialysis have an exceedingly high risk of sudden cardiac death (SCD), accounting for 29% of death events, likely relating to their uremic milieu, recurring exposure to fluid and electrolyte fluxes, and underlying cardiovascular pathology. Furthermore, epidemiologic studies have shown that SCD events, as well as mortality and hospitalizations, occur most frequently on the first dialysis day after the long interdialytic gap, suggesting that abrupt fluctuations in the accumulation and removal of electrolytes, fluid, and uremic toxins over the dialysis cycle may be contributory. Some population-based observational studies have suggested that lower dialysate potassium concentrations appear to be associated with a heightened risk of postdialysis cardiac arrest in hemodialysis patients, although the optimal serum-to-dialysate potassium gradient remains unclear. Some observational studies have suggested that low dialysate calcium concentrations and high serum-to-dialysate calcium gradients may predispose patients to SCD. There is ongoing controversy about an association between higher dialysate bicarbonate concentrations and higher risk of cardiac arrest, likely owing to confounding by indication. Some observational studies also have shown that large interdialytic weight gains, fluid retention, and high ultrafiltration rates are linked with higher risk of SCD and mortality. However, there remains considerable controversy regarding the pros and cons of designating a specific upper ultrafiltration limit with extended treatment times as a clinical practice measure, and further studies are needed to define the optimal tools, metrics, targets, and implementation measures for volume control in the hemodialysis population. In this review, we highlight the epidemiology and pathophysiology of how specific aspects of the hemodialysis procedure may relate to the risk of SCD, as well as preventative strategies and future research directions that can address this risk.

Ouabain Induces Apoptotic Cell Death Through Caspase- and Mitochondria-dependent Pathways in Human Osteosarcoma U-2 OS Cells.

BACKGROUND/AIM: Ouabain, a plant-derived product/substance with Na+/K+-ATPase inhibiting properties, has been shown to exert anti-cancer activity on human cancer cells. This is the first study to investigate the effect of ouabain on apoptotic cell death of human osteosarcoma-derived U-2 OS cells. MATERIALS AND METHODS: Flow cytometry was used to examine cell viability, cell cycle, and reactive oxygen species (ROS), Ca2+, mitochondrial membrane potential (MMP) and caspase activity. Morphological changes were examined by contrast-phase microscopy, while apoptosis-associated protein levels were analyzed by western blot. RESULTS: Ouabain, at concentrations of 5-60 µM, significantly decreased the total viable cells and induced cell morphological changes in a time-dependent manner. It also time-dependently decreased G0/G1 phase and increased S and G2/M phase in U-2 OS cells. The production of ROS and the levels of MMPs (ΔΨm) were inhibited, while Ca2+ production in U-2 OS cells was increased. Regarding cell apoptosis, flow cytometry assay revealed increased caspase-3, -8, and -9 activities in U-2 OS cells. Moreover, western blot results showed that ouabain increased the expression of pro-apoptotic protein Bax and decreased the expression of anti-apoptotic protein Bcl-2 in U-2 OS cells. Furthermore, results also showed that ouabain increased cytochrome c release, apoptosis-inducing factor (AIF) and endonuclease (Endo) G that is associated with apoptosis through caspase-dependent and -independent pathway in U-2 OS cells. CONCLUSION: Our findings provide important insight into the cytotoxic effects of ouabain on U-2 OS cells, in vitro, which are mediated at least partly via cell apoptosis induction.

Association of Ultrafiltration Rate with Mortality in Incident Hemodialysis Patients.

BACKGROUND/AIMS: Ultrafiltration rate (UFR) appears to be associated with mortality in prevalent hemodialysis (HD) patients. However, the association of UFR with mortality in incident HD patients remains unknown. METHODS: We examined a US cohort of 110,880 patients who initiated HD from 2007 to 2011. Baseline UFR was divided into 5 groups (<4, 4 to <6, 6 to <8, 8 to <10, and ≥10 mL/h/kg body weight [BW]). We examined predictors of higher baseline UFR using logistic regression and the association of baseline UFR and all-cause and cardiovascular (CV) mortality using Cox proportional hazard models with adjustments for demographics, comorbidities, and markers of malnutrition-inflammation-cachexia syndrome. RESULTS: Patients were 63 ± 15 years, with 43% women, 32% African Americans, and had a mean baseline UFR of 7.5 ± 3.1 mL/h/kg BW. In the fully adjusted logistic regression models, factors associated with higher UFR (≥7.5 mL/h/kg BW) included Hispanic ethnicity, diabetes, and higher dietary protein intake. There was a linear association between UFR and all-cause and CV mortality, where UFR ≥10 mL/h/kg BW (reference UFR 6-<8 mL/h/kg BW) conferred the highest risk in both unadjusted (HR 1.15 [95% CI 1.10-1.19]) and adjusted models (HR 1.23 [95% CI 1.16-1.31]). The linear association with all-cause mortality remained consistent across strata of age, urine volume, and treatment time. CONCLUSIONS: Higher UFR is independently associated with higher all-cause and CV mortality in incident HD patients. Clinical trials are warranted to examine the effects of lowering UFR on outcomes.

Treatment of massive retroperitoneal hemorrhage from adrenal metastasis of hepatoma.

Spontaneous rupture of metastatic adrenal tumor with massive retroperitoneal hemorrhage and shock is an uncommon clinical event. Herein, we report a case of hepatocellular carcinoma (HCC), where left hepatic lobectomy and right adrenalectomy for metastatic HCC were performed in April and August 2002, respectively. Subsequently, the patient presented to the emergency room with acute-onset severe left flank and back pain in March 2004, accompanied by a falling hemoglobin level. Computed tomography revealed a 7-cm left adrenal tumor mass with retroperitoneal hemorrhage. The ruptured adrenal tumor was further confirmed by selective angiography, which demonstrated that the bleeder was supplied by the left suprarenal artery. Transarterial embolization (TAE) to stop tumor bleeding was performed successfully. The patient then underwent tumor resection with left adrenalectomy 5 days after the embolization, with pathology subsequently revealing metastatic HCC. The recurrent intrahepatic HCC was controlled with TAE, and the patient underwent hormone replacement therapy with prednisolone 10 mg/day. Metastatic adrenal tumor bleeding should be suspected in hepatoma patients who suffer abrupt flank pain and shock. Hemodynamically unstable patients require supportive transfusions and urgent surgical exploration. Angiographic embolization, if deemed feasible, may be a valuable adjunct for achievement of hemostasis prior to definite surgery.