Expert

Jacob Oleck
Aug 1, 2016; 29:180-184
Pharmacy and Therapeutics

(Wiley) Heart failure and cancer are conditions with a number of shared characteristics. A new study published in the Journal of Internal Medicine found that in patients with heart failure, several known tumor markers can also be indicators of heart failure severity and progression.

(Oregon State University) Clinical trial data behind drug dose recommendations for elevated cholesterol and chronic obstructive pulmonary disease illustrate how larger doses may not be worth the extra costs for many types of patients.

Objectives: Radioactive iodine (¹³¹I) therapy may be used to treat thyroid cancer in end-stage renal disease patients who undergo hemodialysis. Because iodine predominantly utilizes renal clearance, treatment management in hemodialysis patients may be problematic, and no formal recommendations on hemodialysis currently exist. This work details our experience with treating thyroid cancer with iodine in chronic renal failure patients who require hemodialysis and details the therapeutic dosimetry results obtained during treatment to ensure that the dose to the bone marrow (BM) was acceptable. Methods: We treated 6 patients in the metabolic radiotherapy unit after thyroid stimulation. Two hemodialysis sessions in the metabolic radiotherapy unit were performed at 42 and 90 hours after radiopharmaceutical administration. BM toxicity was estimated with activity measurements from blood samples and with whole-body measurements that were regularly repeated during hospitalization and measured with a gamma counter. The patients underwent thyroid and hematologic monitoring to assess treatment efficacy and therapeutic toxicity in the short, medium and long term. Results: Whole-body activity was reduced on average by 66.7% [60.1-71.5] after the first dialysis session and by 53.3% [30.4-67.8] after the second. The mean estimated total absorbed dose to the BM was 0.992 Gy for all patients [0.431 – 2.323]. We did not observe any significant hematologic toxicity, and the clinical, biological and ultrasound test results confirmed the success of ablative treatment for the majority of patients. Conclusion: An approximately 30% reduction from the nominal dose in the amount of ¹³¹I activity for hemodialysis patients with thyroid cancer appears to strike an appropriate balance between the absence of BM toxicity and therapeutic efficacy. To avoid overirradiation, we recommend pretherapeutic dosimetry studies for metastatic patients to calculate the amount of activity to be administered as well as dosimetry monitoring during the hemodialysis sessions performed after therapeutic dose administration and under the same conditions.

Research Event

Event participants

Alan Doss, President, Kofi Annan Foundation
 

When you register an Oracle table to the metadata, it might fail and generate an error similar to the following: "ERROR: An exception has been encountered...ERROR: Read Access Violation METALIB..."

If a bulk-loading process fails when you use SAS with SAS/ACCESS Interface to Oracle, you will receive the warning: "WARNING: All or some rows were rejected/discarded.: The actual error is "SQL*Loader-2026: The load was aborted because SQL

When the problem occurs, you are unable to perform any workflow actions in a SAS solution that uses SAS Workflow Services.

A sign-on to a grid-enabled environment fails while it is trying to communicate with the client host. The following errors then appear in the SAS log:

When you run the Copy Files task in SAS Enterprise Guide and there is no connection to a SAS server, it fails with the following error: "ERROR: Target folder does not exist or cannot be accessed."

In SAS  High-Performance Risk, a STRESS task might fail with a message like the following in the SAS log while the compute server is sending the ScenarioCF/Value data to the HPRisk Engine:

When you attempt to save a report distribution in SAS Visual Analytics Designer, you might see the error shown in the following display:  imgalt="" src="{fusion_65868_1_distributionerror.png}" />

In type 2 diabetes, β-cells endure various forms of cellular stress, including oxidative stress and endoplasmic reticulum stress, secondary to increased demand for insulin production and extracellular perturbations, including hyperglycemia. Chronic exposure to stress causes impaired insulin secretion, apoptosis, and loss of cell identity, and a combination of these processes leads to β-cell failure and severe hyperglycemia. Therefore, a better understanding of the molecular mechanisms underlying stress responses in β-cells promises to reveal new therapeutic opportunities for type 2 diabetes. In this perspective, we discuss posttranscriptional control of gene expression as a critical, but underappreciated, layer of regulation with broad importance during stress responses. Specifically, regulation of mRNA translation occurs pervasively during stress to activate gene expression programs; however, the convenience of RNA sequencing has caused translational regulation to be overlooked compared with transcriptional controls. We highlight the role of RNA binding proteins in shaping selective translational regulation during stress and the mechanisms underlying this level of regulation. A growing body of evidence indicates that RNA binding proteins control an array of processes in β-cells, including the synthesis and secretion of insulin. Therefore, systematic evaluations of translational regulation and the upstream factors shaping this level of regulation are critical areas of investigation to expand our understanding of β-cell failure in type 2 diabetes.

6 November 2019 , Volume 95, Number 6

21 February 2020

Active maintenance of β-cell identity through fine-tuned regulation of key transcription factors ensures β-cell function. Tacrolimus, a widely used immunosuppressant, accelerates onset of diabetes after organ transplantation, but underlying molecular mechanisms are unclear. Here we show that tacrolimus induces loss of human β-cell maturity and β-cell failure through activation of the BMP/SMAD signaling pathway when administered under mild metabolic stress conditions. Tacrolimus-induced phosphorylated SMAD1/5 acts in synergy with metabolic stress–activated FOXO1 through formation of a complex. This interaction is associated with reduced expression of the key β-cell transcription factor MAFA and abolished insulin secretion, both in vitro in primary human islets and in vivo in human islets transplanted into high-fat diet–fed mice. Pharmacological inhibition of BMP signaling protects human β-cells from tacrolimus-induced β-cell dysfunction in vitro. Furthermore, we confirm that BMP/SMAD signaling is activated in protocol pancreas allograft biopsies from recipients on tacrolimus. To conclude, we propose a novel mechanism underlying the diabetogenicity of tacrolimus in primary human β-cells. This insight could lead to new treatment strategies for new-onset diabetes and may have implications for other forms of diabetes.

We know that the number of people living with multiple health conditions is rising year on year, and yet training, guidelines, organisations and physical spaces in healthcare still largely focus on single diseases or organ systems. The means that patients in the NHS are often treated as if their conditions exist in isolation, and that their care...

Western Bureau: Some displaced Iberostar employees in Rose Hall, St James, are angry with their employer, charging that they have been unable to benefit from the Government’s COVID-19 relief programme because of the hotel’s failure to pay over...

Inflammation contributes to ventricular remodeling after myocardial ischemia, but its role in nonischemic heart failure is poorly understood. Local tissue inflammation is difficult to assess serially during pathogenesis. Although ¹⁸F-FDG accumulates in inflammatory leukocytes and thus may identify inflammation in the myocardial microenvironment, it remains unclear whether this imaging technique can isolate diffuse leukocytes in pressure-overload heart failure. We aimed to evaluate whether inflammation with ¹⁸F-FDG can be serially imaged in the early stages of pressure-overload–induced heart failure and to compare the time course with functional impairment assessed by cardiac MRI. Methods: C57Bl6/N mice underwent transverse aortic constriction (TAC) (n = 22), sham surgery (n = 12), or coronary ligation as an inflammation-positive control (n = 5). MRI assessed ventricular geometry and contractile function at 2 and 8 d after TAC. Immunostaining identified the extent of inflammatory leukocyte infiltration early in pressure overload. ¹⁸F-FDG PET scans were acquired at 3 and 7 d after TAC, under ketamine-xylazine anesthesia to suppress cardiomyocyte glucose uptake. Results: Pressure overload evoked rapid left ventricular dilation compared with sham (end-systolic volume, day 2: 40.6 ± 10.2 μL vs. 23.8 ± 1.7 μL, P < 0.001). Contractile function was similarly impaired (ejection fraction, day 2: 40.9% ± 9.7% vs. 59.2% ± 4.4%, P < 0.001). The severity of contractile impairment was proportional to histology-defined myocardial macrophage density on day 8 (r = –0.669, P = 0.010). PET imaging identified significantly higher left ventricular ¹⁸F-FDG accumulation in TAC mice than in sham mice on day 3 (10.5 ± 4.1 percentage injected dose [%ID]/g vs. 3.8 ± 0.9 %ID/g, P < 0.001) and on day 7 (7.8 ± 3.7 %ID/g vs. 3.0 ± 0.8 %ID/g, P = 0.006), though the efficiency of cardiomyocyte suppression was variable among TAC mice. The ¹⁸F-FDG signal correlated with ejection fraction (r = –0.75, P = 0.01) and ventricular volume (r = 0.75, P < 0.01). Western immunoblotting demonstrated a 60% elevation of myocardial glucose transporter 4 expression in the left ventricle at 8 d after TAC, indicating altered glucose metabolism. Conclusion: TAC induces rapid changes in left ventricular geometry and contractile function, with a parallel modest infiltration of inflammatory macrophages. Metabolic remodeling overshadows inflammatory leukocyte signal using ¹⁸F-FDG PET imaging. More selective inflammatory tracers are requisite to identify the diffuse local inflammation in pressure overload.

OBJECTIVE

To characterize the status of cardiometabolic risk factors after late relapse of type 2 diabetes mellitus (T2DM) and to identify factors predicting relapse after initial diabetes remission following bariatric surgery to construct prediction models for clinical practice.

Poverty and poor or non-existent health insurance coverage might worsen the effects of heart failure, the American Heart Association said Thursday.

OBJECTIVE

To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

OBJECTIVE

Although blood pressure variability is increasingly appreciated as a risk factor for cardiovascular disease, its relationship with heart failure (HF) is less clear. We examined the relationship between blood pressure variability and risk of HF in two cohorts of type 2 diabetes participating in trials of glucose and/or other risk factor management.

The Trump administration failed to conduct effective screening of passengers from South Korea and Italy for the coronavirus when those countries were experiencing rapid expansion in COVID-19 cases.

OBJECTIVE

We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up.

[S.i.] : [publisher not identified]

The Minneapolis district—with large achievement gaps between white and black students—is enlisting parents from communities of color to help it gather broader and better feedback on how to improve.

Emilia Athayde, Assis Azevedo, Michelli Barros, Víctor Leiva.

Source: Brazilian Journal of Probability and Statistics, Volume 33, Number 2, 301--328.

Abstract:
The Birnbaum–Saunders (BS) distribution has been largely studied and applied. A random variable with BS distribution is a transformation of another random variable with standard normal distribution. Generalized BS distributions are obtained when the normally distributed random variable is replaced by another symmetrically distributed random variable. This allows us to obtain a wide class of positively skewed models with lighter and heavier tails than the BS model. Its failure rate admits several shapes, including the unimodal case, with its change-point being able to be used for different purposes. For example, to establish the reduction in a dose, and then in the cost of the medical treatment. We analyze the failure rates of generalized BS distributions obtained by the logistic, normal and Student-t distributions, considering their shape and change-point, estimating them, evaluating their robustness, assessing their performance by simulations, and applying the results to real data from different areas.

Hongbin Zhang, Lang Wu.

Source: The Annals of Applied Statistics, Volume 13, Number 4, 2140--2157.

Abstract:
For a time-to-event outcome with censored time-varying covariates, a joint Cox model with a linear mixed effects model is the standard modeling approach. In some applications such as AIDS studies, mechanistic nonlinear models are available for some covariate process such as viral load during anti-HIV treatments, derived from the underlying data-generation mechanisms and disease progression. Such a mechanistic nonlinear covariate model may provide better-predicted values when the covariates are left censored or mismeasured. When the focus is on the impact of the time-varying covariate process on the survival outcome, an accelerated failure time (AFT) model provides an excellent alternative to the Cox proportional hazard model since an AFT model is formulated to allow the influence of the outcome by the entire covariate process. In this article, we consider a nonlinear mixed effects model for the censored covariates in an AFT model, implemented using a Monte Carlo EM algorithm, under the framework of a joint model for simultaneous inference. We apply the joint model to an HIV/AIDS data to gain insights for assessing the association between viral load and immunological restoration during antiretroviral therapy. Simulation is conducted to compare model performance when the covariate model and the survival model are misspecified.

Veteran musher Lance Mackey has had his 21st place finish in this year's Iditarod Trail Sled Dog Race vacated because of a failed drug test, race officials announced Thursday.

Digital camera specialist DxOMark on Thursday released a comprehensive review of the front-facing selfie camera on Apple's iPhone 11, finding the device to offer good, if not great, performance compared to competing smartphones.

Washington, D.C. Newsroom, May 7, 2020 / 07:55 am (CNA).- Pope Francis has accepted the resignation of Bishop Joseph Binzer, Cincinnati's auxiliary bishop, who was accused in August of failing to act on allegations made against a priest. 

A statement from the Holy See press office May 7 said the pope had accepted the 65-year-old bishop’s resignation but gave no reason for the decision. 

In a statement released by the Archdiocese of Cincinnati, Archbishop Dennis Schnurr said the pope accepted Binzer’s resignation after conversations between the bishop and the Holy See. 

The archdiocese also included a brief statement from Binzer in which he said he was “deeply sorry for my role in addressing the concerns raised about Father Drew, which has had a negative impact on the trust and faith of the people of the Archdiocese of Cincinnati.”  

“In April, having studied this matter since last summer, the Holy See informed me that it agreed with this assessment. As a result, and after much prayer and reflection, I offered my resignation from the Office of Auxiliary Bishop of the Archdiocese of Cincinnati,” said Binzer. ”I believe this to be in the best interest of the archdiocese.”

Archbishop Schnurr said that although retired, Binzer will continue to serve in the archdiocese with the title of “Auxiliary Bishop Emeritus.” 

“What exactly that ministry will look like will be determined after discussions between Bishop Binzer, the Priest Personnel Board, and me,” Schnurr said. “In this difficult and unfortunate time, please keep Bishop Binzer and all the people of the archdiocese in your prayers.”

Archbishop Schnurr removed Binzer from his position as head of priest personnel in August, after CNA presented officials with its investigation into claims that Binzer failed to pass on reports that a priest had engaged in inappropriate behavior with teenage boys.

In August last year, Schnurr told CNA that “We obviously made serious mistakes in our handling of this matter, for which we are very sorry.”

While Schnurr’s public comments did not address Binzer’s role directly, senior sources in the archdiocese told CNA in August that Schnurr had “gone nuclear” when he discovered the situation.

“The archbishop was as mad as I have ever seen him. When he was told that Bishop Binzer had withheld information, well, he used words I have never heard him use before,” one senior source told CNA, saying Schnurr called Binzer’s actions a “firestorm” for the archdiocese.

In September, 2019, an archdiocesan spokesperson told CNA that Schnurr had sent a "full report to Rome on the whole case and he is waiting for the Vatican’s response,” and he expected "a full investigation” to be conducted by the Vatican.

Binzer later resigned as a member of the U.S. bishops’ conference committee for the protection of children and young people, on which he represented Region VI.

CNA reported in August last year that Binzer was told in 2013 about allegations concerning a recently suspended priest, Fr. Geoff Drew, and failed to disclose them to Cincinnati Archbishop Dennis Schnurr and other archdiocesan officials.

While the archdiocesan victims’ assistance coordinator, who reported to Binzer, was aware of the allegation, the information was not made known to the diocesan priest personnel board or Archbishop Schnurr. 

In 2015, similar allegations were again made against Drew. The matter was forwarded to Butler County officials, who determined that the activity was not criminal. Again, Binzer reported neither the complaints nor the investigation to the archbishop or informed the priest personnel board.

Sources in the archdiocesan chancery told CNA in August that Binzer met with Drew twice, was assured by him that he would reform his conduct, and considered this sufficient.

In early 2018, Drew applied for a transfer to St. Ignatius of Loyola Parish in Green Township, which is attached to the largest Catholic school in the archdiocese.

As head of priest personnel, Binzer was in charge of the process that considers requests and proposals for reassignment, in conjunction with the priest personnel board.

Neither the board nor the archbishop were made aware of the multiple complaints against Drew, and the transfer was approved.

The allegations were also reportedly not recorded by Binzer in the priest’s personnel file that would have been available to the archdiocesan personnel board as part of the process.

A month after Drew’s arrival at St. Ignatius, a parishioner at Drew’s former parish resubmitted the 2015 complaints about the priest, but this time it was also brought to the attention of Archbishop Schnurr.

Also in 2018, Binzer received an additional complaint of similarly inappropriate contact by Drew, dating to his time as a high school music teacher, before his ordination as a priest. 

Following a diocesan investigation, Drew was ordered to attend counselling with a psychologist.

On July 23, Drew was removed from ministry, when it emerged that he had sent a series of inappropriate text messages to a 17-year-old. 

Chancery sources told CNA in August that it was only after the recent incident at St. Ignatius that archdiocesan officials discovered that the otherwise undisclosed complaints about Drew had been made to Binzer, and that the auxiliary bishop had failed to report them to other diocesan officials, or raise them during the decision to approve his transfer in 2018.

CNA Staff, Apr 22, 2020 / 05:02 pm (CNA).- A Sri Lankan priest criticized the government’s response to last year’s Easter bombings, saying the failure to thoroughly investigate has amounted to a betrayal of the people.

Father Nishantha Cooray spoke to Aid to the Church in Need (ACN) on the first anniversary of the bombings that targeted numerous sites across the country, including three churches, on April 21, 2019. The Easter attacks claimed over 259 lives and injured at least 500 more.

Police made 135 arrests following the attacks. Former president of Sri Lanka Maithripala Sirisena created a presidential commission to look into the perpetrators behind the bombings. Current President Gotabaya Rajapaksa appointed a similar committee.

But Cooray, who ministered at victims’ funerals, argued that the actions undertaken so far are inadequate. He warned that if the government does not take the investigation more seriously, it could lead to more attacks in the future.

“Although we have completed one year [since the bombings], no acceptable step has been taken in arresting the persons involved in the crime,” he said.

The priest argued that politicians made promises of a thorough investigation, and gained votes by doing so, but have not followed through on these promises.

“The newly elected government started the second chapter of the same book with the same writing style… They did not want to hurt the Muslim politicians,” he said.

“Now, we feel as if we are betrayed. Just to arouse the emotions of the people, the representatives of the government say something about the investigations [into the bombings]. It is only a good slogan for the next election.”

The Catholic Bishops' Conference of Sri Lanka has appealed to the government to appoint an independent commission to conduct an impartial inquiry.

Commemorating the attacks on their one-year anniversary, parishes in Sri Lanka rang church bells, encouraged people to observe a two-minute period of silence, and lit lamps in memory of the dead victims.

While public Masses have been canceled in Sri Lanka because of the COVID-19 pandemic, Cardinal Malcolm Ranjith of Colombo live-streamed Easter Mass on April 12. During the live stream, Ranjith voiced forgiveness for the attackers.

“[W]e meditated on Christ's teachings and loved them, forgave them and had pity on them,” he said, according to Vatican News.

“We did not hate them and return them the violence. Resurrection is the complete rejection of selfishness,” the cardinal said.

 

A Christian football coach experiences what he says is the best gift from God, something “so much more than winning”.

A welder's life is renewed in Kaharlyk, Ukraine through a new business opportunity with OM.

Mardi Gras in New Orleans has always had a gothic element. The voodoo culture dates from the African American diaspora, though it’s now mostly for tourists. But this year there was an authentically macabre dimension to Fat Tuesday.