bluuebunny/crossref_metadata_2025 huggingface dataset:
Cyclopiazonic Acid Is a Pathogenicity Factor for Aspergillus flavus and a Promising Target for Screening Germplasm for Ear Rot Resistance
Authors: Chalivendra Subbaiah C. , DeRobertis Catherine , Chang Perng-Kuang , Damann Kenneth E.
Published: March 2017

Aspergillus flavus, an opportunistic pathogen, contaminates maize and other key crops with carcinogenic aflatoxins (AFs). Besides AFs, A. flavus makes many more secondary metabolites (SMs) whose toxicity in insects or vertebrates has been studied. However, the role of SMs in the invasion of plant hosts by A. flavus remains to be investigated. Cyclopiazonic acid (CPA), a neurotoxic SM made by A. flavus, is a nanomolar inhibitor of endoplasmic reticulum calcium ATPases (ECAs) and a potent inducer of cell death in plants. We hypothesized that CPA, by virtue of its cytotoxicity, may serve as a key pathogenicity factor that kills plant cells and supports the saprophytic life style of the fungus while compromising the host defense response. This proposal was tested by two complementary approaches. A comparison of CPA levels among A. flavus isolates indicated that CPA may be a determinant of niche adaptation, i.e., isolates that colonize maize make more CPA than those restricted only to the soil. Further, mutants in the CPA biosynthetic pathway are less virulent in causing ear rot than their wild-type parent in field inoculation assays. Additionally, genes encoding ECAs are expressed in developing maize seeds and are induced by A. flavus infection. Building on these results, we developed a seedling assay in which maize roots were exposed to CPA, and cell death was measured as Evans Blue uptake. Among >40 maize inbreds screened for CPA tolerance, inbreds with proven susceptibility to ear rot were also highly CPA sensitive. The publicly available data on resistance to silk colonization or AF contamination for many of the lines was also broadly correlated with their CPA sensitivity. In summary, our studies show that i) CPA serves as a key pathogenicity factor that enables the saprophytic life style of A. flavus and ii) maize inbreds are diverse in their tolerance to CPA. Taking advantage of this natural variation, we are currently pursuing both genome-wide and candidate gene approaches to identify novel components of maize resistance to Aspergillus ear rot.
Preadmission Oral Corticosteroids Are Associated With Reduced Risk of Acute Respiratory Distress Syndrome in Critically Ill Adults With Sepsis*
Authors: McKown Andrew C. , McGuinn Erin M. , Ware Lorraine B. , Wang Li , Janz David R. , Rice Todd W. , Semler Matthew W.
Published: March 2017

Objectives:

To determine the association between preadmission oral corticosteroid receipt and the development of acute respiratory distress syndrome in critically ill patients with sepsis.

Design:

Retrospective observational study.

Setting:

Medical, surgical, trauma, and cardiovascular ICUs of an academic medical center.

Patients:

A total of 1,080 critically ill patients with sepsis.

Interventions:

None.

Measurements and Main Results:

The unadjusted occurrence rate of acute respiratory distress syndrome within 96 hours of ICU admission was 35% among patients who had received oral corticosteroids compared with 42% among those who had not (p = 0.107). In a multivariable analysis controlling for prespecified confounders, preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome in the 96 hours after ICU admission (odds ratio, 0.53; 95% CI, 0.33–0.84; p = 0.008), a finding that persisted in multiple sensitivity analyses. The median daily dose of oral corticosteroids among the 165 patients receiving oral corticosteroids, in prednisone equivalents, was 10 mg (interquartile range, 5–30 mg). Higher doses of preadmission oral corticosteroids were associated with a lower incidence of acute respiratory distress syndrome (odds ratio for 30 mg of prednisone compared with 5 mg 0.53; 95% CI, 0.32–0.86). In multivariable analyses, preadmission oral corticosteroids were not associated with in-hospital mortality (odds ratio, 1.41; 95% CI, 0.87–2.28; p = 0.164), ICU length of stay (odds ratio, 0.90; 95% CI, 0.63–1.30; p = 0.585), or ventilator-free days (odds ratio, 1.06; 95% CI, 0.71–1.57; p = 0.783).

Conclusions:

Among ICU patients with sepsis, preadmission oral corticosteroids were independently associated with a lower incidence of early acute respiratory distress syndrome.
Reinduction of PD1-inhibitor therapy: first experience in eight patients with metastatic melanoma
Authors: Blasig Hanna , Bender Carolin , Hassel Jessica C. , Eigentler Thomas K. , Sachse Michael M. , Hiernickel Julia , Koop Anika , Satzger Imke , Gutzmer Ralf
Published: March 2017

Significant progress has been made in the treatment of metastatic melanoma during the last years. Approval of immune-checkpoint inhibitors and targeted therapies has been achieved recently. The sequencing of these therapies is an important issue. Here, we report our experience with the treatment and retreatment with PD1-inhibitors (PD1i) in eight patients. The patients (two female and seven male with a median age of 70 years, all melanoma stage IV, M1c) underwent a first treatment period with PD1i for a median of 5.5 months. Three (37.5%) patients had a stable disease as best response, two (25%) showed progression, two (25%) showed partial response, and one (12.5%) achieved complete remission. PD1i was discontinued due to disease progression in seven patients and due to side effects (pancreatitis) in one patient. Patients were subsequently treated with ipilimumab (n=2), or chemotherapy (n=4), or no other medical treatment (n=2). All eight patients were subsequently retreated with PD1i for a median of 2.5 months. One (12.5%) developed a partial response, whereas in three patients (37.5%) the disease was stabilized. PD1i have shown a high and durable response rate in the first-line treatment of metastatic melanoma. Our study suggests PD1i retreatment as a reasonable option for selected patients. Further investigations are needed to verify the value of PD1i re-exposure and to identify subgroups of patients who can benefit.
The Experience of Intense Pain
Authors: Kiser-Larson Norma
Published: March 2017

Personal stories of illness give depth to otherwise clinical descriptions of diagnoses. This article offers an autobiographical narrative of complications after total knee replacement surgery. Diagnosis and nursing management of acute compartment syndrome, nociceptive and neuropathic origins of pain, pharmacologic and nursing interventions for pain, the use of prayer in illness, and compassionate caring from a Christian perspective are discussed.
Cardiovascular Risks in Long Distance Runners
Authors: Witham Bethany Rolfe , Babbitt Keven
Published: March 2017

Distance running has become increasingly popular since the 1970s. Despite the health benefits, long-distance running has been associated with an increased risk for cardiac events. Healthcare professionals should be familiar with distance running cardiac risk factors and preparticipation screening recommendations from the American Heart Association, and should screen and educate patients during healthcare encounters. Nurses are particularly well suited to educate runners on risks and symptoms of cardiac dysfunction.
Increasing Utilization of Minimally Invasive Hysterectomy
Authors: WALTERS MARK D. , RIDGEWAY BERI M.
Published: March 2017

Once the decision to perform a hysterectomy has been made, the type and route of hysterectomy must be chosen, and efforts made to accomplish the surgery as safely as possible. Hysterectomy can be performed vaginally, abdominally with laparoscopic or robotic assistance, or open. The main goal of gynecologic surgeons should be to lower the rate of open abdominal hysterectomy and increase use of both vaginal and laparoscopic hysterectomy in their patients. We discuss efforts to accomplish a greater use of minimally invasive hysterectomy.
VITRECTOMY FOR INTERMEDIATE AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH TANGENTIAL VITREOMACULAR TRACTION
Authors: Ziada Jean , Hagenau Felix , Compera Denise , Wolf Armin , Scheler Renate , Schaumberger Markus M. , Priglinger Siegfried G. , Schumann Ricarda G.
Published: March 2017

Purpose:

To describe the morphologic characteristics of the vitreomacular interface in intermediate age-related macular degeneration associated with tangential traction due to premacular membrane formation and to correlate with optical coherence tomography (OCT) findings and clinical data.

Methods:

Premacular membrane specimens were removed sequentially with the internal limiting membrane from 27 eyes of 26 patients with intermediate age-related macular degeneration during standard vitrectomy. Specimens were processed for immunocytochemical staining of epiretinal cells and extracellular matrix components. Ultrastructural analysis was performed using transmission electron microscopy. Spectral domain optical coherence tomography images and patient charts were evaluated in retrospect.

Results:

Immunocytochemistry revealed hyalocytes and myofibroblasts as predominant cell types. Ultrastructural analysis demonstrated evidence of vitreoschisis in all eyes. Myofibroblasts with contractile properties were observed to span between folds of the internal limiting membrane and vitreous cortex collagen. Retinal pigment epithelial cells or inflammatory cells were not detected. Mean visual acuity (Snellen) showed significant improvement from 20/72 ± 20/36 to 20/41 ± 20/32 (P < 0.001) after a mean follow-up period of 19 months (median, 17 months). During this period, none of the eyes required anti–vascular endothelial growth factor therapy.

Conclusion:

Fibrocellular premacular proliferation in intermediate age-related macular degeneration predominantly consists of vitreous collagen, hyalocytes, and myofibroblasts with contractile properties. Vitreoschisis and vitreous-derived cells appear to play an important role in traction formation of this subgroup of eyes. In patients with intermediate age-related macular degeneration and contractile premacular membrane, release of traction by vitrectomy with internal limiting membrane peeling results in significantly functional and anatomical improvement.
Use of Crossed Polarizers to Enhance Images of the Eyelids
Authors: O'Sullivan Ryan , Tom Lisa M. , Bunya Vatinee Y. , Nyberg William C. , Massaro-Giordano Mina , Daniel Ebenezer , Smith Eli , Brainard David H. , Gee James , Maguire Maureen G. , Stone Richard A.
Published: March 2017

Purpose:

To describe imaging of the external eye with Crossed Polarizers to enhance clinically important features in digital photographs of the eyelids.

Methods:

External photographs with and without crossed polarizing filters were taken of patients with blepharitis and controls with no clinical eye pathology.

Results:

Photographing eyelid skin through Crossed Polarizers decreased reflections on the skin surface and improved visualization of eyelid telangiectasias and blood vessels in patients with a broad range of skin pigmentation and ethnicities.

Conclusions:

The use of Crossed Polarizers in imaging the external eye reduces reflections and glare from the eyelid skin and margins, thereby allowing for a more detailed evaluation of underlying structures and analysis of images. These findings suggest that including Crossed Polarizers in clinical photography has informative applications for assessing eyelid disease.
Effect of Sleep Position on the Ocular Surface
Authors: Alevi David , Perry Henry D. , Wedel Alexander , Rosenberg Eric , Alevi Limor , Donnenfeld Eric D.
Published: March 2017

Purpose:

Dry eye disease is a multifactorial disease with numerous well-documented risk factors. However, to date, sleep position has not been associated with this condition. After observing patients in our practice, we believe that the sleep position in some cases may significantly affect dry eye and meibomian gland dysfunction (MGD).

Methods:

This is a single-centered, cross-sectional, noninterventional, institutional review board–approved, single-masked, nonrandomized study of 100 patients whose complaints were related to dry eye disease and a control group of 25 age-matched asymptomatic patients. Two questionnaires were used: one to analyze patients' sleep habits and the other to assess patients' Ocular Surface Disease Index. Dry eye severity was graded based on the MGD stage, fluorescein corneal staining and lissamine green staining, Schirmer 1 testing, tear osmolarity levels, and clinical examination.

Results:

A statistically significant difference was shown with back sleeping compared with left side sleeping using lissamine green staining (analysis of variance, P = 0.005). The Ocular Surface Disease Index score was also found to be elevated in patients who slept on their right or left side (36.4 and 34.1, respectively) as opposed to back sleepers (26.7) with P < 0.05. There was no statistically significant correlation found between the sleep position and degree of MGD.

Conclusions:

In addition to current treatment, patients who sleep on their side or face down might see a reduction in dry eye and MGD if they change their sleep pattern to the supine position.
In Vitro Evaluation of the Drug Reservoir Function of Human Amniotic Membrane Using Moxifloxacin as a Model Drug
Authors: Yelchuri Madhavi Latha , Madhavi Bhagyashree , Gohil Nilam , Sajeev Hitha Sara , Venkatesh Prajna Namperumalsamy , Srinivasan Senthilkumari
Published: March 2017

Purpose:

To evaluate the in vitro, extended drug reservoir function of human amniotic membrane (HAM) of different thicknesses impregnated with moxifloxacin.

Methods:

HAM buttons (12 mm) were soaked with freshly prepared 0.5% wt/vol topical moxifloxacin at different soaking time intervals: 3 hours (group I), 6 hours (group II), 12 hours (group III), 24 hours (group IV), and 48 hours (group V). They were then transferred into 1 mL of fresh simulated tear fluid (pH-7.4) and incubated at 37°C. The release kinetics of moxifloxacin was studied by analyzing the amount of drug in simulated tear fluid collected at different time intervals from each pretreated HAM for 3 weeks. In another experiment, thin and thick HAMs were selected based on weight and soaked with moxifloxacin for 24 hours, and the release kinetics was studied for 7 weeks. All samples were stored at −80°C until analysis by high-performance liquid chromatography.

Results:

No significant difference was observed between different soaking times and the release of moxifloxacin. The cumulative amount of moxifloxacin released from thick HAM was found to be statistically significant compared with thin HAM (P < 0.05).

Conclusions:

Our in vitro data showed that the sustained release of moxifloxacin from HAM was achieved up to 7 weeks. The entrapment efficiency of moxifloxacin was significantly higher in thicker HAM than in thin HAM. Moxifloxacin-impregnated HAM application can be considered in bacterial keratitis to provide sustained drug delivery through a biological bandage system for up to a period of 7 weeks.
Repeat Keratoplasty for Failed Deep Anterior Lamellar Keratoplasty in Keratoconus: Incidence, Indications, and Outcomes
Authors: Feizi Sepehr , Javadi Mohammad Ali , Khajuee-Kermani Pejman , Jafari Roya
Published: March 2017

Purpose:

To analyze the incidence, indications, and clinical outcomes of penetrating keratoplasty (PK) and repeat deep anterior lamellar keratoplasty (DALK) after failed DALK for keratoconus.

Methods:

This retrospective interventional case series reviewed the medical records of patients with keratoconus who underwent DALK and were followed up for at least 1 year. Patients who underwent PK or repeat DALK for failed DALK were identified. The incidence, indications, and clinical outcomes after repeat keratoplasty were assessed.

Results:

A total of 382 consecutive eyes with keratoconus underwent DALK over a 9-year period. Graft failure was observed in 14 eyes (3.7%). The reasons for the graft failure included nonhealing epithelial defects (n = 1), pseudoanterior chamber (n = 2), patient dissatisfaction with vision (n = 4), interface opacification (n = 4), high astigmatism (n = 1), and recurrence of keratoconus in the graft (n = 2). Of these 14 eyes with graft failure, 12 eyes underwent PK (n = 11) or repeat DALK (n = 1). At the most recent examination, which was performed 49.7 ± 25.2 months after the secondary graft, all regrafts were clear. There was no significant difference between eyes with clear first grafts and eyes that underwent PK or repeat DALK in visual outcomes at the final examination. Graft rejection was the most common complication, which was encountered in 75% of the regrafts.

Conclusions:

The prognosis for repeat keratoplasty was excellent, and the outcomes of secondary grafts were comparable to those of primary DALK grafts. However, the rate of rejection with secondary grafts was high, necessitating close follow-up after PK and repeat DALK performed for failed DALK.
Meibomian Gland Dysfunction in Patients With Chemotherapy-Induced Lacrimal Drainage Obstruction
Authors: Eom Youngsub , Baek Sehyun , Kim Hyo Myung , Song Jong Suk
Published: March 2017

Purpose:

To investigate the relationship between chemotherapy-induced lacrimal drainage (LD) obstruction and obstructive meibomian gland dysfunction.

Methods:

Twenty patients who had received chemotherapy were divided into 2 groups, according to the presence of LD obstruction: the LD obstruction group (n = 10) and control group (n = 10). Upper and lower meibomian gland loss was evaluated using noncontact meibography, and tear film lipid layer thickness was measured using an interferometer. The mean values of the right and left eyes of each patient were used to compare parameters between both groups.

Results:

The LD obstruction group had higher levels of meibomian gland loss in both upper (42.9% ± 16.4%) and lower meibomian glands (80.1% ± 16.7%) than did the control group (17.3% ± 6.7% and 22.8% ± 13.0%, respectively) (P < 0.001 and P < 0.001, respectively). In the LD obstruction group, meibomian gland loss in the lower eyelid was significantly higher than that in the upper eyelid (P < 0.001). The lipid layer was significantly thinner in the LD obstruction group (28.4 ± 9.7 nm) than it was in the control group (72.9 ± 22.5 nm) (P < 0.001).

Conclusions:

Patients with chemotherapy-induced LD obstruction had greater meibomian gland loss and thinner lipid layers than did patients without LD obstruction. Chemotherapeutic agents that induce LD obstruction can also block the meibomian gland orifice, resulting in obstructive meibomian gland dysfunction through the same mechanism.
Fever and Hip Pain
Authors: Waseem Muhammad , Kumari Divya , Toledano Talya
Published: March 2017

Hip pain in febrile children always raises concern for septic arthritis. Pyomyositis is a rare cause of hip pain. Because it involves muscles around the joint, it may have a similar presentation as a septic hip. This entity therefore has the potential for posing a diagnostic dilemma when physicians face a limping child with fever. We report a child who presented with fever and hip pain and has pyomyositis of the obturator internus muscle. This case underscores the need to consider the possibility of alternative etiologies in a limping child.
Translating Comparative Effectiveness Research Into Practice: Effects of Interventions on Lifestyle, Medication Adherence, and Self-care for Type 2 Diabetes, Hypertension, and Obesity Among Black, Hispanic, and Asian Residents of Chicago and Houston, 2010 to 2013
Authors: Rashid Jamila R. , Leath Brenda A. , Truman Benedict I. , Atkinson Donna Durant , Gary Lisa C. , Manian Nanmathi
Published: March 2017

Context:

In the United States, racial/ethnic minorities account for disproportionate disease and death from type 2 diabetes, hypertension, and obesity; however, interventions with measured efficacy in comparative effectiveness research are often not adopted or used widely in those communities.

Objective:

To assess implementation and effects of comparative effectiveness research–proven interventions translated for minority communities.

Design:

Mixed-method assessment with pretest–posttest single-group evaluation design.

Setting:

US Department of Health and Human Services, Office of Minority Health, research contractor, and advisory board; health centers, including a federally qualified community health center in Chicago, Illinois; and public housing facilities for seniors in Houston, Texas.

Participants:

A total of 97 black, Hispanic, and Asian participants with any combination of health care provider–diagnosed type 2 diabetes, hypertension, or obesity.

Interventions:

Virtual training institutes where intervention staff learned cultural competency methods of adapting effective interventions. Health educators delivered the Health Empowerment Lifestyle Program (HELP) in Chicago; community pharmacists delivered the MyRx Medication Adherence Program in Houston.

Main Outcome Measures:

Participation rates, satisfaction with interventions during January to April 2013, and pre- to postintervention changes in knowledge, diet, and clinical outcomes were analyzed through July 2013.

Results:

In Chicago, 38 patients experienced statistically significant reductions in hemoglobin A1c and systolic blood pressure, increased knowledge of hypertension management, and improved dietary behaviors. In Houston, 38 subsidized housing residents had statistically nonsignificant improvements in knowledge of self-management and adherence to medication for diabetes and hypertension but high levels of participation in pharmacist home visits and group education classes.

Conclusion:

Adaptation, adoption, and implementation of HELP and MyRx demonstrated important postintervention changes among racial/ethnic participants in Chicago and Houston. The communities faced similar implementation challenges across settings, targets of change, and cities. Available resources were insufficient to sustain benefits with measurable impact on racial/ethnic disparities beyond the study period. Results suggest the need for implementation studies of longer duration, greater power, and salience to policies and programs that can sustain longterm interventions on a community-wide scale.
Early Evaluation Findings From a Federally Funded Training Program: The Public Health Associate Program
Authors: Sobelson Robyn K. , Young Andrea C. , Wigington Corinne J. , Duncan Heather
Published: March 2017

Objective:

The Centers for Disease Control and Prevention (CDC) created the Public Health Associate Program (PHAP) to establish a continuous source of public health professionals who can deliver frontline services at the federal, state, tribal, local, and territorial levels. The article describes preliminary evaluation findings for PHAP.

Design:

The evaluation's primary purposes are to assess the quality and effectiveness of PHAP, determine its value and impact, and provide information to continuously improve the program. Because the evaluation is both formative and summative and focuses on aggregate outputs and outcomes of PHAP, the methodology is complex and builds over time as different cohorts cycle into and out of the program. Results presented are outcomes of various Web-based surveys and reporting systems.

Participants:

Four PHAP cohorts, consisting of 579 individuals, participated in 1 or more of the evaluation activities described in this article.

Results:

The majority of participants report satisfaction with their PHAP experiences, and 74% of recent graduates indicate they are continuing their careers or education in public health immediately after program completion. Seventy-eight percent of recent PHAP graduates who accept a job in public health are employed by the federal government. One year post-PHAP, 74% of alumni report that PHAP has been influential in their careers.

Conclusion:

CDC's investment in PHAP has increased the capacity and capabilities of the public health workforce. Results presented are early indicators of program quality, effectiveness, and impact. Today's public health workers are asked to do more with less, in the face of a dynamic array of complex public health challenges. PHAP offers public health agencies assistance in tackling these losses and challenges.
Early Childhood Education to Promote Health Equity: A Community Guide Economic Review
Authors: Ramon Ismaila , Chattopadhyay Sajal K. , Barnett W. Steven , Hahn Robert A.
Published: March 2017

Context:

A recent Community Guide systematic review found that early childhood education (ECE) programs improve educational, social, and health-related outcomes and advance health equity because many are designed to increase enrollment for high-risk children. This follow-up economic review examines how the economic benefits of center-based ECE programs compare with their costs.

Evidence Acquisition:

Kay and Pennucci from the Washington State Institute for Public Policy, whose meta-analysis formed the basis of the Community Guide effectiveness review, conducted a benefit-cost analysis of ECE programs for low-income children in Washington State. We performed an electronic database search using both effectiveness and economic key words to identify additional cost-benefit studies published through May 2015. Kay and Pennucci also provided us with national-level benefit-cost estimates for state and district and federal Head Start programs.

Evidence Synthesis:

The median benefit-to-cost ratio from 11 estimates of earnings gains, the major benefit driver for 3 types of ECE programs (ie, state and district, federal Head Start, and model programs), was 3.39:1 (interquartile interval [IQI] = 2.48-4.39). The overall median benefit-to-cost ratio from 7 estimates of total benefits, based on all benefit components including earnings gains, was 4.19:1 (IQI = 2.62-8.60), indicating that for every dollar invested in the program, there was a return of $4.19 in total benefits.

Conclusions:

ECE programs promote both equity and economic efficiency. Evidence indicates there is positive social return on investment in ECE irrespective of the type of ECE program. The adoption of a societal perspective is crucial to understand all costs and benefits of ECE programs regardless of who pays for the costs or receives the benefits.
SyMRI of the Brain
Authors: Hagiwara Akifumi , Warntjes Marcel , Hori Masaaki , Andica Christina , Nakazawa Misaki , Kumamaru Kanako Kunishima , Abe Osamu , Aoki Shigeki
Published: March 2017

Conventional magnetic resonance images are usually evaluated using the image signal contrast between tissues and not based on their absolute signal intensities. Quantification of tissue parameters, such as relaxation rates and proton density, would provide an absolute scale; however, these methods have mainly been performed in a research setting. The development of rapid quantification, with scan times in the order of 6 minutes for full head coverage, has provided the prerequisites for clinical use. The aim of this review article was to introduce a specific quantification method and synthesis of contrast-weighted images based on the acquired absolute values, and to present automatic segmentation of brain tissues and measurement of myelin based on the quantitative values, along with application of these techniques to various brain diseases. The entire technique is referred to as “SyMRI” in this review. SyMRI has shown promising results in previous studies when used for multiple sclerosis, brain metastases, Sturge-Weber syndrome, idiopathic normal pressure hydrocephalus, meningitis, and postmortem imaging.
Prenatal Diagnosis of Vesicorectal Fistula
Authors: Correia Patricia , Moreira Marta , Rodrigues Maria , Inocêncio Gonçalo
Published: March 2017

Anorectal malformations are a rare condition difficult to diagnose in the prenatal period. It can be suspected if distal bowel appears dilated in the first-trimester ultrasound or if intraluminal echogenic foci are detected during the second-trimester scan. We report a case with these ultrasound signs (dilated sigmoid at the first trimester and intraluminal echogenic calcifications at the second trimester), in which a vesicorectal fistula image was obtained. This is the first published prenatal image of a vesicorectal fistula.
Impact of Surgical Resection of the Primary Tumor on Overall Survival in Patients With Metastatic Pheochromocytoma or Sympathetic Paraganglioma
Authors: Roman-Gonzalez Alejandro , Zhou Shouhao , Ayala-Ramirez Montserrat , Shen Chan , Waguespack Steven G. , Habra Mouhammed A. , Karam Jose A. , Perrier Nancy , Wood Christopher G. , Jimenez Camilo
Published: March 2017

Objective:

To determine whether primary tumor resection in patients with metastatic pheochromocytoma or paraganglioma (PPG) is associated with longer overall survival (OS).

Background:

Patients with metastatic PPG have poor survival outcomes. The impact of surgical resection of the primary tumor on OS is not known.

Methods:

We retrospectively studied patients with metastatic PPG treated at the University of Texas, MD Anderson Cancer Center from January 2000 through January 2015. Kaplan-Meier analysis with log-rank tests was used to compare OS among patients undergoing primary tumor resection and patients not treated surgically. Propensity score method was applied to adjust for selection bias using demographic, clinical, biochemical, genetic, imaging, and pathologic information.

Results:

A total of 113 patients with metastatic PPG were identified. Eighty-nine (79%) patients had surgery and 24 (21%) patients did not. Median OS was longer in patients who had surgery than in patients who did not [148 months, 95% confidence interval (CI) 112.8–183.2 months vs 36 months, 95% CI 27.2–44.8 months; P < 0.001].

Fifty-three (46%) patients had synchronous metastases; of these patients, those who had surgery had longer OS than those who did not (85 months, 95% CI 64.5–105.4 months vs 36 months, 95% CI 29.7–42.3 months; P < 0.001). Patients who had surgery had a similar ECOG performance status to the ones who did not (P = 0.1798, two sample t test; P = 0.2449, Wilcoxon rank sum test). Univariate and propensity score analysis confirmed that patients treated with surgery had longer OS than those not treated surgically irrespective of age, race, primary tumor size and location, number of metastatic sites, and genetic background (log-rank P < 0.001).

In patients with hormonally active tumors (70.8%), the symptoms of catecholamine excess improved after surgery. However, the tumor burden was a more important determinant of OS than hormonal secretion.

Conclusions:

Primary tumor resection in patients with metastatic PPG appeared to be associated with improved OS. In patients with hormonally active tumors, surgical resection led to better blood pressure control.
A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress
Authors: McMurchy Alicia N. , Stempor Przemyslaw , Gaarenstroom Tessa , Wysolmerski Brian , Dong Yan , Aussianikava Darya , Appert Alex , Huang Ni , Kolasinska-Zwierz Paulina , Sapetschnig Alexandra , Miska Eric , Ahringer Julie
Published: March 2017

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set ofC. elegansheterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibitingcep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among these factors and pathways underlies the importance of safeguarding the genome through multiple means.
Crystal structure of diaquabis(4-cyanopyridine-κN)bis(thiocyanato-κN)iron(II) 4-cyanopyridine disolvate
Authors: Jochim Aleksej , Jess Inke , Näther Christian
Published: March 2017

The asymmetric unit of the title compound, [Fe(NCS)2(C6H4N2)2(H2O)2]·2C6H4N2, comprises one FeIIcation occupying an inversion centre as well as one thiocyanate anion, one water molecule and two 4-cyanopyridine molecules in general positions. The iron cations are coordinated by two N-bonded thiocyanate anions, two (pyridine)N-bonded 4-cyanopyridine ligands and two water molecules into discrete complexes. The resulting coordination polyhedron can be described as a slightly distorted octahedron. The discrete complexes are connected through centrosymmetric pairs of (pyridine)C—H...N(cyano) hydrogen bonds into chains that are further linked into a three-dimensional network through intermolecular O—H...N hydrogen bonds involving the 4-cyanopyridine solvent molecules.
Crystal structures ofN-(4-chlorophenyl)-2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide andN-(3-chlorophenyl)-2-[(4,6-diaminopyrimidin-2-yl)sulfanyl]acetamide
Authors: Subasri S. , Kumar Timiri Ajay , Sinha Barij Nayan , Jayaprakash Venkatesan , Viswanathan Vijayan , Velmurugan Devadasan
Published: March 2017

The title compounds, C12H12ClN5OS, (I), and C12H12ClN5OS, (II), are 2-[(diaminopyrimidin-2-yl)sulfanyl]acetamides. Compound (II), crystallizes with two independent molecules (AandB) in the asymmetric unit. In each of the molecules, in both (I) and (II), an intramolecular N—H...N hydrogen bond forms anS(7) ring motif. The pyrimidine ring is inclined to the benzene ring by 42.25 (14)° in (I), and by 59.70 (16) and 62.18 (15)° in moleculesAandB, respectively, of compound (II). In the crystal of (I), molecules are linked by pairs of N—H...N hydrogen bonds, forming inversion dimers with anR22(8) ring motif. The dimers are linkedviabifurcated N—H...O and C—H...O hydrogen bonds, forming corrugated layers parallel to theacplane. In the crystal of (II), theAmolecules are linked through N—H...O and N—H...Cl hydrogen bonds, forming layers parallel to (100). TheBmolecules are also linked by N—H...O and N—H...Cl hydrogen bonds, also forming layers parallel to (100). The parallel layers ofAandBmolecules are linkedviaN—H...N hydrogen bonds, forming a three-dimensional structure.
Self-reported reasons for voluntary abstinences by adolescent cannabis users
Authors: Marandure Blessing Ngonidzashe , Graham Hermine L.
Published: March 2017

Purpose

Factors influencing cannabis use have been previously identified mainly using multivariate approaches. However, there is a dearth of information collected from the perspective of the adolescent cannabis user, in particular for voluntary abstinences. The paper aims to discuss these issues.

Design/methodology/approach

In total, 38 cannabis users were identified from a sample of 261 adolescents recruited from schools. They completed open-ended questions identifying reasons for voluntary abstinences. Thematic analysis was used to assess their responses.

Findings

Voluntary abstinences by cannabis users were influenced by both internal and external factors. These were the user’s state of mind, an attempt to quit, negative effects of cannabis, prior to important events, prior to family interactions and peers.

Research limitations/implications

The results show that adolescent cannabis users are flexible in their approach to using cannabis, being able to briefly stop when the situation warrants it. However, the study is limited by a lack of in depth and rich data, limiting the scope of the analysis.

Originality/value

This is the first study to identify reasons for voluntary abstinences from the user’s perspective in adolescent cannabis users.
How can schools help to reduce the harm associated with teenage substance use? Development of a theoretically driven whole-school approach
Authors: Markham Wolfgang A. , Bonell Chris , Fletcher Adam , Aveyard Paul
Published: March 2017

Purpose

Substance use prevalence varies considerably between schools, but to date, whole school approaches for reducing substance use have only been moderately effective. The purpose of this paper is to develop a novel multifaceted whole-school approach to reduce substance use primarily among teenagers aged 11-14 years.

Design/methodology/approach

The outlined approach is premised on the proposal that schools can reduce the harms associated with substance use by promoting school connectedness and improving the school-related experiences of weakly connected and disconnected students. The aim of this approach is to develop students’ autonomy so that they may act in their real and long-term interests. This may be attained by promoting the realisation of essential human capacities for: practical reasoning – through valued opportunities for cognitive development and affiliation – through valued opportunities for affective development that advance students sense of acceptance within school. Schools may achieve this, it is proposed, by providing outlined forms of appropriate formal support and formal control that are augmented by particular features of school organisation, curriculum and pedagogic practice, which are also described.

Findings

A theoretically driven understanding of a whole school approach for reducing teenage substance use is outlined.

Originality/value

The outlined approach may usefully inform the development of future whole school interventions aiming to reduce problematic substance use among school students. Additional potential benefits include more successful student life trajectories.
A method for evaluating treatment quality using in vivo EPID dosimetry and statistical process control in radiation therapy
Authors: Fuangrod Todsaporn , Greer Peter B. , Simpson John , Zwan Benjamin J. , Middleton Richard H.
Published: March 2017

Purpose

Due to increasing complexity, modern radiotherapy techniques require comprehensive quality assurance (QA) programmes, that to date generally focus on the pre-treatment stage. The purpose of this paper is to provide a method for an individual patient treatment QA evaluation and identification of a “quality gap” for continuous quality improvement.

Design/methodology/approach

A statistical process control (SPC) was applied to evaluate treatment delivery using in vivo electronic portal imaging device (EPID) dosimetry. A moving range control chart was constructed to monitor the individual patient treatment performance based on a control limit generated from initial data of 90 intensity-modulated radiotherapy (IMRT) and ten volumetric-modulated arc therapy (VMAT) patient deliveries. A process capability index was used to evaluate the continuing treatment quality based on three quality classes: treatment type-specific, treatment linac-specific, and body site-specific.

Findings

The determined control limits were 62.5 and 70.0 per cent of the χ pass-rate for IMRT and VMAT deliveries, respectively. In total, 14 patients were selected for a pilot study the results of which showed that about 1 per cent of all treatments contained errors relating to unexpected anatomical changes between treatment fractions. Both rectum and pelvis cancer treatments demonstrated process capability indices were less than 1, indicating the potential for quality improvement and hence may benefit from further assessment.

Research limitations/implications

The study relied on the application of in vivo EPID dosimetry for patients treated at the specific centre. Sampling patients for generating the control limits were limited to 100 patients. Whilst the quantitative results are specific to the clinical techniques and equipment used, the described method is generally applicable to IMRT and VMAT treatment QA. Whilst more work is required to determine the level of clinical significance, the authors have demonstrated the capability of the method for both treatment specific QA and continuing quality improvement.

Practical implications

The proposed method is a valuable tool for assessing the accuracy of treatment delivery whilst also improving treatment quality and patient safety.

Originality/value

Assessing in vivo EPID dosimetry with SPC can be used to improve the quality of radiation treatment for cancer patients.
Markov chain decision model for urinary incontinence procedures
Authors: Kumar Sameer , Ghildayal Nidhi , Ghildayal Neha
Published: March 2017

Purpose

Urinary incontinence (UI) is a common chronic health condition, a problem specifically among elderly women that impacts quality of life negatively. However, UI is usually viewed as likely result of old age, and as such is generally not evaluated or even managed appropriately. Many treatments are available to manage incontinence, such as bladder training and numerous surgical procedures such as Burch colposuspension and Sling for UI which have high success rates. The purpose of this paper is to analyze which of these popular surgical procedures for UI is effective.

Design/methodology/approach

This research employs randomized, prospective studies to obtain robust cost and utility data used in the Markov chain decision model for examining which of these surgical interventions is more effective in treating women with stress UI based on two measures: number of quality adjusted life years (QALY) and cost per QALY. Treeage Pro Healthcare software was employed in Markov decision analysis.

Findings

Results showed the Sling procedure is a more effective surgical intervention than the Burch. However, if a utility greater than certain utility value, for which both procedures are equally effective, is assigned to persistent incontinence, the Burch procedure is more effective than the Sling procedure.

Originality/value

This paper demonstrates the efficacy of a Markov chain decision modeling approach to study the comparative effectiveness analysis of available treatments for patients with UI, an important public health issue, widely prevalent among elderly women in developed and developing countries. This research also improves upon other analyses using a Markov chain decision modeling process to analyze various strategies for treating UI.
If your market is a competitive dogfight, think like a cat
Authors: Sherman Leonard
Published: March 2017

Purpose

The article helps answer one of the most urgent questions facing corporate leaders: how can a company trapped in a competitive market innovate successful new products that are meaningfully different?

Design/methodology/approach

The article explains how to implement three business-strategy frameworks that have emerged, all of which provide useful guidance to entrepreneurs and corporate innovators seeking to identify meaningfully differentiated products and services that deliver a compelling consumer value proposition.

Findings

The three strategy frameworks reviewed in this article provide insightful perspectives on how companies can break away from the pack to create sizeable opportunities for profitable growth, even in industries that are struggling with sluggish demand and slim profit margins.

Practical implications

Be prepared to disrupt your own business when the inevitable onset of Red Ocean market conditions begins to diminish your prospects for continued profitable growth.

Originality/value

A comprehensive look at product and service differentiation strategies that can focus the hunt for breakthrough innovations.
Partnering with AI: how organizations can win over skeptical managers
Authors: Kolbjørnsrud Vegard , Amico Richard , Thomas Robert J.
Published: March 2017

Purpose

According to the authors’ research, while top-level executives look forward to the potential of artificial intelligent systems in their firms, line managers are much more skeptical. This article advises on i8mplementation strategy.

Design/methodology/approach

Drawing on findings from Accenture’s survey of 1,770 managers in 14 countries and interviews with 37 senior executives responsible for digital transformation, the authors have identified patterns in managers’ attitudes and offer strategies for effective adoption of the new technology.

Findings

When managers have a say and involvement in initial training efforts, they gain a sense of ownership throughout the learning process as well as familiarity with intelligent systems.

Practical implications

The introduction of AI will put a premium on “soft” skills such as collaboration, creativity and good judgment, which may be just as important, if not more important, than technical skills in the future.

Originality/value

The emergence of artificial intelligence (AI) promises to transform the nature of work and the relationship among human beings and machines in organizations. When the authors asked whether leaders would be comfortable with AI monitoring and evaluating their work, 42 percent of the top managers in our survey strongly agreed, while only 15 percent of first-line managers shared the same sentiment.” This research discovered that top executives cannot assume that mid- and lower-level managers will share their appreciation for AI.
Thymoma‐associated multi‐organ autoimmunity: A case of graft‐versus‐host disease‐like erythroderma complicated by Good syndrome successfully treated by thymectomy
Authors: Fukushima Ayano , Ichimura Yoshiko , Obata Shoko , Kinoshita‐Ise Misaki , Fujio Yumi , Takeno Mitsuhiro , Konohana Izumi
Published: March 2017

Thymoma‐associated multi‐organ autoimmunity disease (TAMA) is a rare paraneoplastic disorder, clinicopathologically similar to graft‐versus‐host disease (GVHD). Many reported cases follow a difficult course; half of them die from serious infectious diseases subsequent to immunosuppression induced by chemotherapy for unresectable thymoma, or intensive therapies including systemic steroids for complicating autoimmune diseases and GVHD‐like symptoms. We report a patient whose skin symptoms were improved subsequently to total thymectomy. The patient also presented with hypogammaglobulinemia, which led to the diagnosis of complicated Good syndrome. Taking account of her immunodeficient condition, antibiotics and i.v. immunoglobulin were administrated promptly on onset of bacterial pneumonia, which was successfully treated. According to a review of the published work, treatments with systemic steroids for skin symptoms have limited effects and may contribute to serious infection. Our case indicates that successful treatment of thymoma itself may lead to the amelioration of the disease. The management priority should be given to the treatment of thymoma and the control of subsequent immune abnormality other than GVHD‐like erythroderma.
Arguing a fortiori
Authors: d'Almeida Luís Duarte
Published: March 2017

Courts and lawyers often argue a fortiori. Sometimes they actually use the Latin phrase to indicate that their conclusions do not just follow, but ‘follow a fortiori’ from certain premises. These are taken to be inferences of a distinct and important kind. But how exactly are they distinct, and why are they important? Despite their popularity, a fortiori arguments are not well understood and have not drawn much attention from legal theorists. This paper pursues two goals. The first is to bring out the form of a fortiori arguments, articulating those assumptions that, though typically left unstated, are necessary elements of arguments of this kind. The second goal is to say something about the point of such arguments, and to characterise the sort of context in which an arguer will have reason to deploy an a fortiori rather than an inference of a different type.