Particle shape effects on the stress response of granular packings.

We present measurements of the stress response of packings formed from a wide range of particle shapes. Besides spheres these include convex shapes such as the Platonic solids, truncated tetrahedra, and triangular bipyramids, as well as more complex, non-convex geometries such as hexapods with various arm lengths, dolos, and tetrahedral frames. All particles were 3D-printed in hard resin. Well-defined initial packing states were established through preconditioning by cyclic loading under given confinement pressure. Starting from such initial states, stress-strain relationships for axial compression were obtained at four different confining pressures for each particle type. While confining pressure has the largest overall effect on the mechanical response, we find that particle shape controls the details of the stress-strain curves and can be used to tune packing stiffness and yielding. By correlating the experimentally measured values for the effective Young's modulus under compression, yield stress and energy loss during cyclic loading, we identify trends among the various shapes that allow for designing a packing's aggregate behavior.

Short-term administration of progesterone and estradiol independently alter carotid-vasomotor, but not carotid-cardiac, baroreflex function in young women.

The individual effects of estrogen and progesterone on baroreflex function remain poorly understood. We sought to determine how estradiol (E2) and progesterone (P4) independently alter the carotid-cardiac and carotid-vasomotor baroreflexes in young women by using a hormone suppression and exogenous add-back design. Thirty-two young women were divided into two groups and studied under three conditions: 1) after 4 days of endogenous hormone suppression with a gonadotropin releasing hormone antagonist (control condition), 2) after continued suppression and 3 to 4 days of supplementation with either 200 mg/day oral progesterone (N = 16) or 0.1 to 0.2 mg/day transdermal 17ß-estradiol (N = 16), and 3) after continued suppression and 3 to 4 days of supplementation with both hormones. Changes in heart rate (HR), mean arterial pressure (MAP), and femoral vascular conductance (FVC) were measured in response to 5 s of +50 mmHg external neck pressure to unload the carotid baroreceptors. Significant hormone effects on the change in HR, MAP, and FVC from baseline at the onset of neck pressure were determined using mixed model covariate analyses accounting for P4 and E2 plasma concentrations. Neither P4 (P = 0.95) nor E2 (P = 0.95) affected the HR response to neck pressure. Higher P4 concentrations were associated with an attenuated fall in FVC (P = 0.01), whereas higher E2 concentrations were associated with an augmented fall in FVC (P = 0.02). Higher E2 was also associated with an augmented rise in MAP (P = 0.01). We conclude that progesterone blunts whereas estradiol enhances carotid-vasomotor baroreflex sensitivity, perhaps explaining why no differences in sympathetic baroreflex sensitivity are commonly reported between low and high combined hormone phases of the menstrual cycle.

Flexible partial denture variations. The use of circumferential, combination, and continuous clasp designs.

The new design potential of the flexible partial and its clasp allows for a new treatment approach to the well-established problems of retention, stability, and strength. The 4 main clasp designs include the conventional, the circumferential, the combination, and the continuous clasp. The proper use of these various designs can be a strong foundation upon which to develop the clinical strengths of the flexible partial denture.

When the Islamic State Kills: Ironies of American and ISIS Executions.

These research notes explore the idea of comparing executions in the United States (US) to executions undertaken by the Islamic State of Iraq and Syria (ISIS). Is it possible that America's ostensibly rational, formal, and "clinical" death penalty is more painful for its victims than ISIS victims? I investigate this question by considering the suffering caused by the death penalty in the US, making some informed speculations about ISIS executions, discussing execution in two influential Islamic nations, and observing some ironies these topic raise about the rule of law and capital punishment. My goal with these notes is to spur interest in comparative research on state violence and the death penalty.

Short-term oral progesterone administration antagonizes the effect of transdermal estradiol on endothelium-dependent vasodilation in young healthy women.

Very few studies have explored the cardiovascular effects of progesterone in premenopausal women. This study aimed to examine the short-term effects of oral progesterone alone, transdermal estrogen alone, and progesterone and estrogen combined on flow-mediated dilation (FMD) in healthy reproductive-aged women. We suppressed endogenous estrogens and progesterone in 17 premenopausal women for 10-12 days using a gonadotropin-releasing hormone antagonist. On day 4 (hormone suppression condition), subjects were tested (n = 17) and were then supplemented with either 200 mg micronized progesterone (n = 8) orally or 0.1 mg estradiol (n = 9) transdermally per day. On day 7 (progesterone-first or estradiol-first condition), subjects were tested and began supplementation with both hormones (n = 17) and were tested again on day 10 (combined hormone condition). FMD of the brachial artery was assessed using B-mode arterial ultrasound, combined with synchronized Doppler analysis. As a result, significant differences in FMD were observed between hormone suppression (7.85 ± 1.06%) and estrogen-first conditions (10.14 ± 1.40%; P < 0.05). The estradiol-induced increase was abolished when oral progesterone was also supplemented (6.27 ± 0.96%). In contrast, we observed a trend toward a decrease in FMD with unopposed progesterone administration, but no statistically significant differences were found between the progesterone-first (6.66 ± 1.23%), hormone suppression (7.80 ± 1.23%), and combined hormone conditions (7.40 ± 1.29%). In conclusion, these data suggest that short-term oral micronized progesterone administration antagonizes the beneficial effect of transdermal estradiol on FMD.

17ß-estradiol and progesterone independently augment cutaneous thermal hyperemia but not reactive hyperemia.

OBJECTIVE: We examined the impact of estradiol and progesterone on skin LH and RH in 25 healthy women. METHODS: Subjects were studied three times over 10-12 days. Endogenous sex hormones were suppressed with a GnRHa. Subjects were studied on day 4 of suppression (study day 1), three to four days later following treatment with either 17ß-estradiol or progesterone (study day 2), and another three to four days later, following treatment with both estradiol and progesterone (study day 3). Subjects underwent identical LH and RH protocols on all study days. LH is characterized by an initial peak in blood flow, followed by a prolonged plateau. A brief nadir is seen between the phases. RESULTS: Blood flow values are expressed as percent maximum CVC. Estradiol alone increased initial peak CVC from 71 ± 2% to 79 ± 2% (p = 0.001). Progesterone alone increased initial peak CVC from 72 ± 2% to 78 ± 2% (p = 0.046). Neither estradiol nor progesterone increased plateau CVC. No significant changes were seen between study days 2 and 3 for either group. No differences were observed in RH. CONCLUSIONS: Both estradiol and progesterone increased initial peak CVC during LH, without altering plateau CVC. There was no additive effect of estradiol and progesterone.

Fusion loop peptide of the West Nile virus envelope protein is essential for pathogenesis and is recognized by a therapeutic cross-reactive human monoclonal antibody.

West Nile virus is an emerging pathogen that can cause fatal neurological disease. A recombinant human mAb, mAb11, has been described as a candidate for the prevention and treatment of West Nile disease. Using a yeast surface display epitope mapping assay and neutralization escape mutant, we show that mAb11 recognizes the fusion loop, at the distal end of domain II of the West Nile virus envelope protein. Ab mAb11 cross-reacts with all four dengue viruses and provides protection against dengue (serotypes 2 and 4) viruses. In contrast to the parental West Nile virus, a neutralization escape variant failed to cause lethal encephalitis (at higher infectious doses) or induce the inflammatory responses associated with blood-brain barrier permeability in mice, suggesting an important role for the fusion loop in viral pathogenesis. Our data demonstrate that an intact West Nile virus fusion loop is critical for virulence, and that human mAb11 targeting this region is efficacious against West Nile virus infection. These experiments define the molecular determinant on the envelope protein recognized by mAb11 and demonstrate the importance of this region in causing West Nile encephalitis.

Survey of Radiation Oncologists to Assess Interest and Potential Use of a Genetic Test Predicting Susceptibility for the Development of Toxicities After Prostate Cancer Radiation Therapy.

PURPOSE: A genetic test predicting susceptibility for the development of toxicities after prostate cancer radiation therapy is in development. This test intends to help physicians with treatment decision making. METHODS AND MATERIALS: Radiation oncologists were surveyed using a web-based questionnaire to gauge their interest in using a genetic test predictive of increased risk of radiation therapy toxicities as an aid in determining therapy for men with prostate cancer. Responses were summarized using frequencies, and a χ2 test compared responses among participants. Multivariable ordinal regression identified factors associated with anticipated adoption or nonadoption of such a genetic test by radiation oncologists. RESULTS: Among 204 radiation oncologists (64% from the United States, 36% from other countries), 86.3% would order a genetic test and 80.2% said the test would be useful for treatment discussions. There was wide acceptance (76.7%) to offer a genetic test to all patients considering radiation therapy for prostate cancer. Additionally, 98.1% indicated that patients would be receptive to the test information. There were no significant differences in the likelihood of ordering a genetic test based on practice setting, familiarity with scientific literature, time spent on research, or geographic location (all P > .05). CONCLUSIONS: Radiation oncologists who treat prostate cancer are interested in and willing to order a genetic test predictive of susceptibility to radiation therapy toxicity to aid their treatment decision making.

Clinical Pharmacokinetics and Safety of ALZ-801, a Novel Prodrug of Tramiprosate in Development for the Treatment of Alzheimer's Disease.

BACKGROUND: ALZ-801 is an orally available, valine-conjugated prodrug of tramiprosate. Tramiprosate, the active agent, is a small-molecule ß-amyloid (Aß) anti-oligomer and aggregation inhibitor that was evaluated extensively in preclinical and clinical investigations for the treatment of Alzheimer's disease (AD). Tramiprosate has been found to inhibit ß-amyloid oligomer formation by a multi-ligand enveloping mechanism of action that stabilizes Aß42 monomers, resulting in the inhibition of formation of oligomers and subsequent aggregation. Although promising as an AD treatment, tramiprosate exhibited two limiting deficiencies: high intersubject pharmacokinetic (PK) variability likely due to extensive gastrointestinal metabolism, and mild-to-moderate incidence of nausea and vomiting. To address these, we developed an optimized prodrug, ALZ-801, which retains the favorable efficacy attributes of tramiprosate while improving oral PK variability and gastrointestinal tolerability. In this study, we summarize the phase I bridging program to evaluate the safety, tolerability and PK for ALZ-801 after single and multiple rising dose administration in healthy volunteers. METHODS: Randomized, placebo-controlled, phase I studies in 127 healthy male and female adult and elderly volunteers included [1] a single ascending dose (SAD) study; [2] a 14-day multiple ascending dose (MAD) study; and [3] a single-dose tablet food-effect study. This program was conducted with both a loose-filled capsule and an immediate-release tablet formulation, under both fasted and fed conditions. Safety and tolerability were assessed, and plasma and urine were collected for liquid chromatography-mass spectrometry (LC-MS) determination and non-compartmental PK analysis. In addition, we defined the target dose of ALZ-801 that delivers a steady-state plasma area under the curve (AUC) exposure of tramiprosate equivalent to that studied in the tramiprosate phase III study. RESULTS: ALZ-801 was well tolerated and there were no severe or serious adverse events (AEs) or laboratory findings. The most common AEs were transient mild nausea and some instances of vomiting, which were not dose-related and showed development of tolerance after continued use. ALZ-801 produced dose-dependent maximum plasma concentration (C max) and AUC exposures of tramiprosate, which were equivalent to that after oral tramiprosate, but with a substantially reduced intersubject variability and a longer elimination half-life. Administration of ALZ-801 with food markedly reduced the incidence of gastrointestinal symptoms compared with the fasted state, without affecting plasma tramiprosate exposure. An immediate-release tablet formulation of ALZ-801 displayed plasma exposure and low variability similar to the loose-filled capsule. ALZ-801 also showed excellent dose-proportionality without accumulation or decrease in plasma exposure of tramiprosate over 14 days. Based on these data, 265 mg of ALZ-801 twice daily was found to achieve a steady-state AUC exposure of tramiprosate equivalent to 150 mg twice daily of oral tramiprosate in the previous phase III trials. CONCLUSIONS: ALZ-801, when administered in capsule and tablet forms, showed excellent oral safety and tolerability in healthy adults and elderly volunteers, with significantly improved PK characteristics over oral tramiprosate. A clinical dose of ALZ-801 (265 mg twice daily) was established that achieves the AUC exposure of 150 mg of tramiprosate twice daily, which showed positive cognitive and functional improvements in apolipoprotein E4/4 homozygous AD patients. These bridging data support the phase III development of ALZ-801in patients with AD.

The pathology of extrapulmonary small cell carcinoma.

Extrapulmonary small cell carcinomas (EPSCCs) are uncommon malignant neoplasms with a reported incidence of 0.1% to 0.4% in the United States. Since their first description in 1930, they have been seen in nearly every organ system. Like their more common pulmonary counterparts, EPSCCs are thought to arise from a multipotential stem cell. However, there is recent molecular evidence that small cell elements may arise as a late-stage phenomenon in the genetic progression of more organ-typical carcinomas. The morphologic, immunohistochemical, and ultrastructural features are similar to those described in pulmonary small cell carcinomas (PSCCs). The differential diagnosis of EPSCC includes PSCC, other neuroendocrine tumors, small round blue cell tumors, metastatic melanoma, lymphoma, and poorly differentiated non-small cell carcinomas. Molecular alterations reported to occur in EPSCCs include abnormalities described in PSCC and changes found in carcinomas more typically encountered in the organ from which they arise. In this article we discuss the pathology of EPSCC with a review of theories of histogenesis, sites of occurrence, diagnostic features, differential diagnosis, molecular alterations, and clinical behavior.

Monoclonal antibodies specific for Bacteroides fragilis enterotoxins BFT1 and BFT2 and their use in immunoassays.

We have developed 22 mouse IgG1 monoclonal antibodies (mAbs) against Bacteroides fragilis zinc metalloprotease toxins 1 and 2 (BFT1 and BFT2). Mice were immunized with recombinant BFT1 or BFT2 proteins with metalloprotease activity. Eight of the mAbs bind specifically to BFT1. One mAb, 2H6, binds specifically to BFT2. The remaining 13 mAbs bind to both BFT1 and BFT2. The eight BFT1-specific mAbs recognize at least five different epitopes on the toxin. Four of the BFT1-specific mAbs neutralized rBFT1 metalloprotease activity. Only one of these four mAbs, 1D9, neutralizes the cytotoxic effect of BFT1. Here, we describe the development of enzyme-linked immunosorbent assays (ELISAs) to detect BFT1 or BFT2 toxin in an isotype-specific manner. The sandwich ELISAs have a detection limit of 20 to 40 ng/ml when purified recombinant BFT protein is diluted into PBS. The sandwich ELISA can be used to distinguish and quantify levels of rBFT1 and rBFT2 in stool. This ELISA can be an important tool to investigate the association between BFT expression by enterotoxigenic B. fragilis and diseases such as diarrhea, inflammatory bowel disease and colorectal cancer.

Glia induce dendritic growth in cultured sympathetic neurons by modulating the balance between bone morphogenetic proteins (BMPs) and BMP antagonists.

Dendritic growth in cultured sympathetic neurons requires specific trophic interactions. Previous studies have demonstrated that either coculture with glia or exposure to recombinant bone morphogenetic proteins (BMPs) is both necessary and sufficient to induce dendrite formation. These observations led us to test the hypothesis that BMPs mediate glial-induced dendritic growth. In situ hybridization and immunocytochemical studies indicate that the spatiotemporal expression of BMP5, -6, and -7 in rat superior cervical ganglia (SCG) is consistent with their proposed role in dendritogenesis. In vitro, both SCG glia and neurons were found to express BMP mRNA and protein when grown in the presence or absence of the other cell type. However, addition of ganglionic glia to cultured sympathetic neurons causes a marked increase in BMP proteins coincident with a significant decrease in follistatin and noggin. Functional assays indicate that glial-induced dendritic growth is significantly reduced by BMP7 antibodies and completely inhibited by exogenous noggin and follistatin. These data suggest that glia influence the rapid perinatal expansion of the dendritic arbor in sympathetic neurons by increasing BMP activity via modulation of the balance between BMPs and their antagonists.

1D5 and 6F11: An immunohistochemical comparison of two monoclonal antibodies for the evaluation of estrogen receptor status in primary breast carcinoma.

The optimal monoclonal antibody to examine steroid hormone receptor status of primary breast carcinoma has yet to be defined. Estrogen receptor status was evaluated in 592 cases using routinely prepared paraffin-embedded tissue samples from primary breast carcinomas with the 1D5 (DAKO, Carpinteria, CA) and 6F11 (Novocastra, Newcastle upon Tyne, England) monoclonal antibodies. The stains were compared, assessing the percentage of positive cells stained and their intensity. They also were examined for nonspecific cytoplasmic staining and fixation artifact. In addition, a cost analysis for their production was performed. Overall, 1D5 and 6F11 showed a 97.5% concordance rate. 6F11 stained a significantly higher percentage of cells (P < .0001), more intensely (P < .0001), with less nonspecific cytoplasmic staining (P < .0001). There was no significant difference in fixation artifact between the 2 clones. The cost of antibody used for preparing a 1D5-stained slide was 86% more than for preparing a 6F11-stained slide (dollars 14.27 vs dollars 7.67).

Melanosis of the uterine cervix: a case report.

BACKGROUND: Melanosis of the uterine cervix is a rare, benign, melanocytic lesion of the cervix. A review of the English-language literature revealed 11 other reported cases. CASE: A 52-year-old African American woman who presented for evaluation and treatment of menorrhagia was found to have an irregular, pigmented cervical lesion. The ectocervical biopsy showed melanosis characterized by hyperkeratosis, acanthosis and prominent elongation of rete with abundant basilar pigmentation. Immunohistochemical staining showed scattered, basally situated, S-100 protein-positive melanocytes. CONCLUSION: The existence of this entity is further evidence of a spectrum of melanocytic lesions, including blue nevi and primary melanomas, known to occur within the cervix proper.

Villous adenocarcinoma of the colon and rectum: a clinicopathologic study of 36 cases.

Some colorectal adenocarcinomas show villous architecture with morphologic similarities to tubulovillous or villous adenomas. We reviewed 420 consecutive colorectal adenocarcinoma resection specimens and found that 95 tumors (23%) showed areas of villous architecture. Thirty-six tumors (8.6%) in 35 patients showed more than 50% villous architecture and were designated villous adenocarcinomas. Only 42% of the villous adenocarcinomas showed severe atypia and only 44% of the available pre-resection biopsies of these tumors were diagnosed as adenocarcinoma. Epithelial islands in desmoplastic stroma (EIDS) may be helpful in the diagnosis of these tumors. EIDS were found in 97% of the resection specimens for villous adenocarcinomas and none of 62 resection specimens for tubulovillous or villous adenomas. The presence of EIDS showed a 67% sensitivity, 100% specificity, and 100% predictive value in the diagnosis of villous adenocarcinoma in a blinded review of villous tumors. On review of the pre-resection biopsies of villous adenocarcinoma without a final diagnosis of adenocarcinoma, 40% showed EIDS. Clinical follow-up of the 35 patients with villous adenocarcinoma showed that only one died of colorectal adenocarcinoma (median follow-up, 46 months). This sole patient dying of colorectal adenocarcinoma showed a synchronous advanced stage of nonvillous adenocarcinoma at the time of diagnosis. Villous adenocarcinoma is a diagnostically challenging subset of colorectal adenocarcinoma, which appears to be associated with a favorable prognosis. Classifying these tumors as a special type of colorectal cancer may facilitate the development of diagnostic adjuncts and optimal treatment protocols.

Beneficial effects of intraventricularly administered BMP-7 following a striatal 6-hydroxydopamine lesion.

The present study was undertaken to investigate the effects of bone morphogenetic protein-7 (BMP-7), also named osteogenic protein-1 (OP-1), on the progression of a striatal 6-hydroxydopamine (6-OHDA) lesion. BMP-7, a member of the transforming growth factor-beta (TGF-beta) superfamily of proteins, has been shown to have protective effects in other animal models of neuronal damage. In this study, male Fischer 344 rats received striatal 6-OHDA lesions followed 1 week later by an intraventricular dose of BMP-7. No significant effect of BMP-7 treatment on spontaneous locomotor activity was observed, however BMP-7 significantly increased the density of tyrosine hydroxylase (TH) immunoreactivity (TH-ir) in the substantia nigra (SN) pars compacta, in the lesioned hemisphere [31.7+/-5.2 (optical density (O.D.) arbitrary units) control vs. 50.2+/-4.3 O.D. BMP-7-treated; p<0.05]. Interestingly, BMP-7 significantly increased TH-ir in the SN of the non-lesioned hemisphere (pars reticulata: 14.8+/-1.19 O.D. control vs. 36+/-2.6 O.D. BMP-7-treated, p<0.05; pars compacta: 29.0+/-4.9 O.D. control vs. 64.4+/-6.9 O.D. BMP-7-treated, p<0.001). A significant increase in DA concentration in the contralateral, non-lesioned hemisphere was also noted (113.2 ng/g control vs. 198.2 ng/g BMP-7-treated, p<0.01). In contrast to other intraventricularly administered neurotrophic factors, BMP-7 was not associated with an increase in the sensitivity to pain. These results suggest that BMP-7 is able to act as a dopaminotrophic agent without unwanted side effects and as such may be a useful pharmacological tool in the treatment of Parkinson's disease in humans.

Cycle fecundity in controlled ovarian hyperstimulation and intrauterine insemination. Influence of the number of mature follicles at hCG administration.

OBJECTIVE: To determine if cycle fecundity in controlled ovarian hyperstimulation (COH) with intrauterine insemination (IUI) cycles is influenced by the number of mature follicles at the time of hCG administration. STUDY DESIGN: Retrospective data analysis of 75 infertility patients undergoing 164 consecutive COH/IUI cycles with FSH and/or hMG in a university-affiliated private infertility center. Cycles were compared for number of mature follicles (> or = 15 mm) and peak serum estradiol levels, total number of ampules and days of gonadotropin use, and clinical pregnancy rate. RESULTS: There was a statistically significant increase in cycle fecundity when three to four mature follicles were stimulated. Peak estradiol levels were significantly different in the groups, as predicted from the number of follicles. The groups were not statistically different in age or etiology of infertility. Group A (1-2 mature follicles) required significantly more FSH/hMG than group B (3-4 follicles) or group C (> or = 5 follicles). CONCLUSION: In COH/IUI cycles, three to four mature follicles yield improved cycle fecundity as compared to that in cycles with a smaller or larger number of follicles. These findings may help identify patients who will be more successful in conceiving with COH/IUI versus those who should be counseled to use other assisted reproductive technologies.

Evaluation of dietary patterns in dogs with cardiac disease.

OBJECTIVE: To determine the dietary patterns and intake of nutrients of concern in dogs with cardiac disease. DESIGN: Prospective study. ANIMALS: 82 dogs with dilated cardiomyopathy (DCM) or chronic valvular disease. PROCEDURE: Owners of dogs were contacted and given a standardized telephone questionnaire regarding diet and a 24-hour food recall to determine daily intake of calories, protein, fat, sodium, potassium, and magnesium. RESULTS: Among the 82 dogs, 71% had no congestive heart failure (CHF), and 29% had CHF or a history of CHF. Sixty-one percent of dogs had concurrent diseases. Anorexia was or had been evident in 34% of dogs and was significantly more common in the CHF group and in dogs with DCM. Most dogs (92%) received some treats and table food, with a median percentage of daily calories from treats of 19% (range, 0% to 100%). Most owners (57%) that administered pills used human or pet foods for pill administration. Most dogs ate more than the Association of American Feed Control Officials (AAFCO) minimum values for fat and protein. Daily sodium intake varied from 14 to 384 mg/100 kcal, compared with the AAFCO minimum of 17 mg/100 kcal. A median of 25% of total daily sodium came from treats and table food (range, 0% to 100%). Dogs with CHF ate significantly more sodium, compared with dogs with no CHF. CONCLUSIONS AND CLINICAL RELEVANCE: Dietary intake for dogs with cardiac disease is highly variable and often not optimal.

Characteristics of scheduled bleeding manipulation with combined hormonal contraception in university students.

BACKGROUND: There is a lack of information concerning the decision factors and sources of information influencing women who purposefully deviate from the prescribed use of their combined hormone contraceptives to exert elective control of their scheduled bleeding. STUDY DESIGN: A self-administered email survey of scheduled bleeding practices and beliefs was distributed to 11,900 female students at the University of Oregon. Assessment of survey participant characteristics, scheduled bleeding manipulation features and attitudes and knowledge toward hormonal contraception was analyzed. RESULTS: Of 1719 respondents to the survey, 1374 (79.9%) reported using combined hormonal contraception currently or recently. Approximately 17% of these women altered their scheduled bleeding pattern by deviating from package instructions. Of these, 50% indicated they delayed or skipped their scheduled bleeding for convenience or personal choice. Within this group, 47% of women indicated they learned to modify their scheduled bleeding from health care professionals, while 30% indicated such knowledge was obtained from family or friends. Characteristics that decreased the likelihood of this practice included being of Asian race, use of hormonal contraceptive for bleeding cycle regulation, following a regular exercise program, and personal preference for a monthly cycle. CONCLUSIONS: The majority of university females who choose to modify their scheduled bleeding cycle with combined hormonal contraceptives do so for convenience rather than to avoid menstrual symptoms, and many learn from nonmedical sources. There is some disparity between the preferences of menstruation frequency and actual scheduled bleeding pattern behaviors, suggesting potential for improvement in patient education.