Effects of cinnamaldehyde or monensin on performance of weaned Holstein dairy heifers.

The objective of this 70-d study was to determine the effects of the essential oil cinnamaldehyde compared with the ionophore monensin on performance of weaned Holstein dairy heifers. Eighty-four Holstein dairy heifers (91 ± 3.33 d of age; 109 ± 7.55 kg) were housed in a naturally ventilated curtain sidewall, straw-bedded barn in 12 pens with 7 heifers/pen (3.98 m2/head). Heifers were randomly assigned to 1 of 4 treatments in a completely randomized design: (1) control (CON; carrier, 908 g of ground corn), (2) monensin sodium [MON; 1 mg/kg of body weight (BW) + carrier], (3) cinnamaldehyde (CIN1; 1 mg/kg of BW + carrier), or (4) cinnamaldehyde (CIN2; 2 mg/kg of BW + carrier). The treatments were hand-mixed into a 20% crude protein (CP) whole shelled corn and protein pellet mix fed at 2.21 kg/heifer daily. Heifers had access to free-choice hay and water daily. Initial BW and hip heights were taken at the start of the study and every other week thereafter until calves reached 23 wk of age. Blood samples were also taken on each weigh day to determine plasma urea nitrogen, glucose, and insulin-like growth factor-1 concentrations. Fecal samples were taken from the same 3 heifers/pen initially and then at d 28, 56, and 70 of the study for coccidia counts. Cinnamaldehyde had no performance effects on growth, hay intake, hip height, or blood metabolites compared with MON or CON. Average daily gains were 0.98, 0.99, 1.01, and 1.03 kg/d, and average hay intakes per pen were 17.08, 16.34, 18.11, and 17.60 kg/d for CON, MON, CIN1, and CIN2, respectively. Fecal samples by pens indicated the presence of viable coccidia, but the counts were low and not consistent across heifers within each pen. No benefits were associated with supplementing cinnamaldehyde or monensin into grain mixes for weaned heifers.

Highly relativistic radiation belt electron acceleration, transport, and loss: Large solar storm events of March and June 2015.

Two of the largest geomagnetic storms of the last decade were witnessed in 2015. On 17 March 2015, a coronal mass ejection-driven event occurred with a Dst (storm time ring current index) value reaching -223 nT. On 22 June 2015 another strong storm (Dst reaching -204 nT) was recorded. These two storms each produced almost total loss of radiation belt high-energy (E ≳ 1 MeV) electron fluxes. Following the dropouts of radiation belt fluxes there were complex and rather remarkable recoveries of the electrons extending up to nearly 10 MeV in kinetic energy. The energized outer zone electrons showed a rich variety of pitch angle features including strong "butterfly" distributions with deep minima in flux at α = 90°. However, despite strong driving of outer zone earthward radial diffusion in these storms, the previously reported "impenetrable barrier" at L ≈ 2.8 was pushed inward, but not significantly breached, and no E ≳ 2.0 MeV electrons were seen to pass through the radiation belt slot region to reach the inner Van Allen zone. Overall, these intense storms show a wealth of novel features of acceleration, transport, and loss that are demonstrated in the present detailed analysis.

An impenetrable barrier to ultrarelativistic electrons in the Van Allen radiation belts.

Early observations indicated that the Earth's Van Allen radiation belts could be separated into an inner zone dominated by high-energy protons and an outer zone dominated by high-energy electrons. Subsequent studies showed that electrons of moderate energy (less than about one megaelectronvolt) often populate both zones, with a deep 'slot' region largely devoid of particles between them. There is a region of dense cold plasma around the Earth known as the plasmasphere, the outer boundary of which is called the plasmapause. The two-belt radiation structure was explained as arising from strong electron interactions with plasmaspheric hiss just inside the plasmapause boundary, with the inner edge of the outer radiation zone corresponding to the minimum plasmapause location. Recent observations have revealed unexpected radiation belt morphology, especially at ultrarelativistic kinetic energies (more than five megaelectronvolts). Here we analyse an extended data set that reveals an exceedingly sharp inner boundary for the ultrarelativistic electrons. Additional, concurrently measured data reveal that this barrier to inward electron radial transport does not arise because of a physical boundary within the Earth's intrinsic magnetic field, and that inward radial diffusion is unlikely to be inhibited by scattering by electromagnetic transmitter wave fields. Rather, we suggest that exceptionally slow natural inward radial diffusion combined with weak, but persistent, wave-particle pitch angle scattering deep inside the Earth's plasmasphere can combine to create an almost impenetrable barrier through which the most energetic Van Allen belt electrons cannot migrate.

The associations between diet quality, Body Mass Index (BMI) and Health and Activity Limitation Index (HALex) in the Geisinger Rural Aging Study (GRAS).

OBJECTIVES: To determine the associations between diet quality, body mass index (BMI), and health-related quality of life (HRQOL) as assessed by the health and activity limitation index (HALex) in older adults. DESIGN: Multivariate linear regression models were used to analyze associations between Dietary Screening Tool (DST) scores, BMI and HALex score, after controlling for gender, age, education, living situation, smoking, disease burden and self-vs. proxy reporting. SETTING: Geisinger Rural Aging Study, Pennsylvania. PARTICIPANTS: 5,993 GRAS participants were mailed HRQOL and DST questionnaires with 4,009 (1,722 male, 2,287 female; mean age 81.5 ± 4.4) providing complete data. RESULTS: HALex scores were significantly lower for participants with dietary intakes categorized as unhealthy (<60) (0.70, 95% CI 0.69, 0.72, p<0.05) or borderline (60-75) (0.71, 95% CI 0.70, 0.73, p<0.05) compared to those scoring in the healthy range (>75) (0.75, 95% CI 0.73, 0.77) based on DST scores. HALex scores were significantly lower for underweight (0.67, 95% CI 0.63, 0.72, p<0.05), obese class II (0.68, 95% CI 0.66, 0.71, p<0.05) and class III participants (0.62 95% CI 0.57, 0.67, p<0.05) compared to those with BMI 18.5-24.9. CONCLUSIONS: Poor diet quality, as assessed by the DST, is associated with lower HRQOL in adults ≥ 74 years of age.

Visual and non-visual factors associated with patient satisfaction and quality of life in LASIK.

PURPOSE: The aim of this study was to determine how laser in situ keratomileusis (LASIK) affects quality of life (QOL) and to identify factors that may affect satisfaction after LASIK. METHODS: A total of 104 patients with a mean age of 29±6, treated with LASIK for myopia and astigmatism, were enrolled in a prospective study. High (90%) and low (10%) contrast visual acuity (CVA) were measured under photopic and scotopic conditions before surgery and at 3 months later. A multidimensional QOL scale (Institute for Eye Research multidimensional QOL scale), which assesses psychological characteristics, personality traits, cosmesis, frequency, and tolerance to disturbing visual and ocular symptoms, and overall satisfaction with vision correction, was also used. Paired rank tests were used to compare preoperative and postoperative vision and QOL scores. Correlations and a multiple linear regression were used to describe the relationship between CVA, QOL, and satisfaction after LASIK. RESULTS: Significant postoperative changes included increased satisfaction following LASIK (P<0.001), reduced frequency of visual and ocular symptoms (P<0.001), and change in psychological characteristics (P=0.033). The change in satisfaction with LASIK can be predicted by a combination of preoperative satisfaction, postoperative frequency of disturbing visual and ocular symptoms, postoperative mean spherical equivalent, and postoperative scotopic high CVA (R (2)=0.725, P<0.05). CONCLUSIONS: Satisfaction with LASIK is related to visual function, preoperative expectations, psychological characteristics, and uncorrected CVA achieved. An increased sense of subjective well-being, adaptability, and self-efficacy was evident after LASIK. Patients reported a more optimistic attitude to life and increase perceived QOL after surgery.

Pre-operative Quality of Life and psychological factors that influence patient decision making in LASIK.

PURPOSE: To assess pre-operative visual function, psychological factors, personality traits and satisfaction in myopic patients seeking laser-assisted in situ keratomileusis (LASIK). METHODS: Eligible patients seeking LASIK (n=183) and successful contact lens wearers (n=23) not interested in LASIK completed the Institute for Eye Research Quality of Life (QOL) Scale. Of the 183 patients seeking LASIK who completed the QOL instrument before LASIK, 30 declined the procedure and 153 underwent LASIK. One hundred and two patients who underwent LASIK attended their 3-month post-operative follow-up appointment and 51 patients failed to present for their post-operative follow-up appointment. Multiple comparisons (One-way Analysis of Variance (ANOVA)) were conducted to determine differences in visual function, psychological factors, personality traits and satisfaction between patient groups. RESULTS: Successful soft contact lens (SCL) wearers reported better functional vision (P=0.001), felt more attractive (P=0.007), had a lower frequency of disturbing visual and ocular symptoms (P=0.027) and higher overall satisfaction with their current optical correction (P<0.001) than patients seeking LASIK. LASIK patients lost to follow-up showed higher self-efficacy, adaptability and well-being than the patients who completed their appointments and those who declined surgery (P<0.05). CONCLUSIONS: Psychological characteristics, the perception of visual and ocular symptoms and satisfaction with the current method of optical correction play an important role in the decision to undergo LASIK. The IER QOL Scale is a valid and reliable instrument able to discriminate between different groups seeking choices for myopic correction. Psychological factors may influence the level of satisfaction with LASIK.

Driving behavior under the influence of cannabis or cocaine.

OBJECTIVE: The purpose of this study is first to describe perceptions of driving under the influence of cannabis or cocaine among clients in treatment and, second, to assess whether these perceptions are related to the frequency of driving under the influence of cannabis or cocaine. METHODS: A questionnaire was administered to clients in treatment for abuse of either cocaine or cannabis, many of whom also had a problem with alcohol; additional groups of clients consisted of those in smoking cessation and gambling programs (N = 1021). Open-ended and close-ended questions were used to assess self-reported effects of cannabis or cocaine on driving and frequency of driving under the influence of cannabis, cocaine, or alcohol. RESULTS: Two dimensions of driving behavior under the influence of cocaine or cannabis were found in both qualitative and quantitative analyses: 1) physical effects and 2) reckless styles of driving. Common physical effects for both drugs were heightened nervousness, greater alertness, and poorer concentration. In terms of driving behavior, cautious or normal driving was commonly reported for cannabis, whereas reckless or reduced driving ability was frequently reported for cocaine. When comparing negative physical effects and reckless style of driving with frequency of driving under the influence of cannabis or cocaine, increased negative physical effects from cannabis were inversely related to frequency of driving under the influence of cannabis (p = .001), but other relationships were not significant. CONCLUSIONS: The findings indicate that both cannabis and cocaine have detrimental but different effects on driving. The negative physical effects of cannabis may reduce the likelihood of driving under the influence of cannabis.

Predicting violence among cocaine, cannabis, and alcohol treatment clients.

In this study, the relationship between the use of various substances, selected psychosocial characteristics, and violence was examined. Groups of subjects in treatment for a primary problem with cocaine (n=300), cannabis (n=128), alcohol (n=110), other drugs (33), tobacco (n=249) or gambling (n=199) completed a self-administered questionnaire. The questionnaire included questions on various psychosocial scales (i.e., aggressive personality, chronic stress, sleep problems, impulsivity, disrespect for the law and social supports), frequency of drug and alcohol use, and violence in the past year. For the univariate analyses, all of the drug and psychosocial variables were significantly related to violence. In the multivariate analyses, frequency of cocaine and alcohol use, disrespect for the law, aggressive personality, age and sex were significantly related to violence. The findings point to multi-causal explanations; however, both alcohol and cocaine use appear to play a significant role in explaining violence.

Theoretical analysis of accommodation amplitude and ametropia correction by varying refractive index in Phaco-Ersatz.

Phaco-Ersatz is a surgical procedure for restoring accommodation in which the presbyopic crystalline lens is replaced by a flexible polymer gel in the lens capsule. We assessed the feasibility of simultaneously correcting ametropia while restoring accommodation using Phaco-Ersatz by utilizing polymer gel of the appropriate refractive index. Computation results using paraxial equations and ray tracing on two model eyes indicate that although this approach might be feasible for the hypermetrope, its usefulness for correcting myopia is limited, principally due to significant reductions in the resultant amplitude of accommodation.

Ophthalmoscopic contact lenses for transpupillary thermotherapy.

Ophthalmoscopic contact lenses for transpupillary thermotherapy (TTT) must provide effective visualization of retinal treatment sites and transmission of infrared diode laser radiation. Selection and proper use of retinal laser lenses requires knowledge of their lateral magnification, laser beam magnification factor, field of view and resolution. Optical performance is analyzed for Goldmann-type lenses and a series of inverted image lenses of differing magnification. Goldmann lenses have the highest resolution, but inverted image lenses of comparable magnification have 2.5 times or more their field of view. Inverted image lenses of similar magnification can differ in resolution. They require 2-4% more incident laser power to produce the same retinal irradiance as a Goldmann lens, but this difference is small in comparison to other clinical variables. Tilting an ophthalmoscopic contact lens up to 15 degrees causes little distortion in the circularity of the retinal spot formed by a laser beam or difference in retinal irradiance across the spot. Inverted image lenses produce higher anterior segment irradiances than Goldmann-type lenses, but anterior segment injuries are less likely in TTT than conventional visible light, short-pulse retinal photocoagulation because of the comparatively low irradiances used in TTT and the decreased absorption of diode laser infrared radiation in ocular media and melanin.

Altered HOX and WNT7A expression in human lung cancer.

HOX genes encode transcription factors that control patterning and cell fates. Alterations in HOX expression have been clearly implicated in leukemia, but their role in most other malignant diseases remains unknown. By using degenerate reverse transcription-PCR and subsequent real-time quantitative assays, we examined HOX expression in lung cancer cell lines, direct tumor-control pairs, and bronchial epithelial cultures. As in leukemia, genes of the HOX9 paralogous group and HOXA10 were frequently overexpressed. For HOXB9, we confirmed that elevated RNA was associated with protein overexpression. In some cases, marked HOX overexpression was associated with elevated FGF10 and FGF17. During development, the WNT pathway affects cell fate, polarity, and proliferation, and WNT7a has been implicated in the maintenance of HOX expression. In contrast to normal lung and mortal short-term bronchial epithelial cultures, WNT7a was frequently reduced or absent in lung cancers. In immortalized bronchial epithelial cells, WNT7a was lost concomitantly with HOXA1, and a statistically significant correlation between the expression of both genes was observed in lung cancer cell lines. Furthermore, we identified a homozygous deletion of beta-catenin in the mesothelioma, NCI-H28, associated with reduced WNT7a and the lowest overall cell line expression of HOXA1, HOXA7, HOXA9, and HOXA10, whereas HOXB9 levels were unaffected. Of note, both WNT7a and beta-catenin are encoded on chromosome 3p, which undergoes frequent loss of heterozygosity in these tumors. Our results suggest that alterations in regulatory circuits involving HOX, WNT, and possibly fibroblast growth factor pathways occur frequently in lung cancer.

Maximizing qualitative responses about smoking in structured interviews.

This article addresses the important methodological issue of whether face-to-face or self-administered interviews elicit better qualitative data on reasons for smoking and quitting among 173 current and former smokers. The data are from a study of smoking behaviors among 601 African American and Latina women age 14 to 21 years recruited from family planning clinics in Los Angeles from 1995 to 1996. Results suggest that responses to closed questions about smoking behavior are similar in both methods but that self-administered surveys elicit more responses to open-ended questions than face-to-face interviews. The authors encourage the use of self-administered surveys in smoking research because they are cheaper to administer, yield similar data on closed-question items, and elicit richer and more provocative responses to open-ended questions.

DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC.

DEF-3(g16/NY-LU-12) encodes a novel RNA binding protein isolated by positional cloning from an SCLC homozygous deletion region in 3p21.3 and, in parallel, as a differentially expressed gene during myelopoiesis from FDCPmix-A4 cells. DEF-3(g16/NY-LU-12) is ubiquitously expressed during mouse embryogenesis and in adult organs while human hematopoietic tissues showed differential expression. The mouse and human proteins are highly conserved containing two RNA recognition motifs (RRMs) and other domains associated with RNA binding and protein-protein interactions. A database search identified related proteins in human, rat, C. elegans and S. pombe including the 3p21.3 co-deleted gene, LUCA15. Recombinant proteins containing the RRMs of DEF-3(g16/NY-LU-12) and LUCA15 specifically bound poly(G) RNA homopolymers in vitro. These RRMs also show similarity to those of the Hu protein family. Since anti-Hu RRM domain antibodies are associated with an anti-tumor effect and paraneoplastic encephalomyelitis, we tested sera from Hu syndrome patients with the RRMs of DEF-3(g16/NY-LU-12) and LUCA15. These were non-reactive. Thus, DEF-3(g16/NY-LU-12) and LUCA15 represent members of a novel family of RNA binding proteins with similar expression patterns and in vitro RNA binding characteristics. They are co-deleted in some lung cancers and immunologically distinct from the Hu proteins.

Introduction: the three phases of harm reduction. An examination of emerging concepts, methodologies, and critiques.

The prevention and reduction of harm related to the use and distribution of psychoactive substances has gone through three stages in the last 35 years of this century. The first saw the articulation of public health concerns for the legal drugs, alcohol and tobacco, and the provision of methadone to heroin users. The second phase, building on the public health lessons of other infectious diseases, focused on illicit drugs and the importance of specific strategies for the prevention of HIV transmission among injection drug users. The third, emerging phase is the shift toward an integrated public health perspective in the convergence of approaches to both licit and illicit drugs. The success of harm reduction as a unifying concept will depend on its innovative application in both prohibitory and regulatory frameworks, and careful evaluation of its effectiveness in a variety of cultural contexts. The papers in this special issue illustrate the types of research and critical thinking that are essential for the continued evolution of the harm-reduction paradigm.

Analysis of TEL proteins in human leukemias.

Chromosomal translocations involving the human 12p13 band frequently affect the TEL gene, usually resulting in gene fusion between TEL and genes encoding proteins of various types. The most frequent 12p13 translocation is the t(12;21)(p13;q22), which recombines TEL with the AML1 gene on chromosome 21 and is frequently associated with deletion of the untranslocated TEL allele. Using antisera against different parts of TEL and against the AML1 proteins, we undertook Western blot and immunofluorescence analyses of leukemic samples with and without 12p13 abnormalities. In t(12;21) samples, TEL-AML1 was detected as several protein species in the nuclei, whereas the AML1-TEL protein, was inconsistently expressed. AML1 was found to be expressed but no normal TEL proteins were detected. A survey of the TEL proteins in a panel of human leukemic samples without t(12;21) revealed a variation in the ratio of TEL protein isoforms. We also analysed a leukemic cell line bearing a t(12;22)(p13;q11) that was found to affect the 5' untranslated (UT) region of TEL and to be associated with inactivation of the untranslocated TEL allele. No MN1-TEL fusion could be detected upon RT-PCR analysis, in contrast to the previously investigated t(12;22). Strikingly, extremely low levels of apparently normal TEL proteins, expressed from the translocated allele, were detected by Western blot analysis. These results suggest that the level of TEL expression can be important for leukemogenesis.

Evaluation of a population-based measure of quality of life: the Health and Activity Limitation Index (HALex).

This paper briefly discusses the rationale and methods for developing and evaluating the Health and Activity Limitation Index (HALex), a generic measure of health that consists of two attributes: perceived health and activity limitation. Using a multiattribute utility scoring system, information from these attributes was combined to form a single score that represents health-related quality of life (QoL) on a 0.0-1.0 continuum. The construct and incremental validity are evaluated using data from a sample of over 40,000 adults who participated in the 1990 US National Health Interview Survey. The health state distributions for known groups, defined in terms of personal or lifestyle characteristics such as sex, age and smoking status, were comparable to those for similarly defined states that have been studied by other researchers. Of the regression models examined in this analysis, age, years of schooling and being in a high-risk group based on body mass index (BMI) were found to have the largest impact on health as measured by the HALex. Although this measure was developed to be combined with mortality data to form a quality-adjusted life year (QALY) for detecting changes in the health of the US population from 1990 to 2000, it may also be useful for inclusion in clinical studies, in particular as the national data are readily available for use as norms.

Pre-clinical evaluation of probes to detect t(8;21) AML minimal residual disease by fluorescence in situ hybridization.

The 8;21 translocation in acute myeloid leukemia (AML) results in a consistent fusion transcript, AML1/ETO. Long-term clinical remission occurs in some patients despite incomplete eradication of AML1/ETO as demonstrated by RT-PCR, thus limiting the usefulness of this assay. An important future goal will be to determine if there is a level of minimal residual disease (MRD) in patients below which relapse is unlikely. For the detection of MRD, we have developed reagents for fluorescence in situ hybridization (FISH) that identify both derivative 8 and 21 chromosomes with a high analytical sensitivity. In t(8;21) AML cells, two fused signals were detected in addition to the normal 8 and 21 alleles. The sensitivity and specificity of this probe mixture were analyzed in cell lines and patient bone marrows. One and two randomly juxtaposed signals were observed in 2.4 and 0.04% of normal cells, respectively. However, these were easily differentiated from t(8;21) cells by the absence of signals from the normal alleles. Using as criteria the presence of two fused signals plus the normal alleles, we observed no false positives among 5,000 normal cells. The probe correctly identified 20/20 patients with t(8;21) AML and 10/10 non-t(8;21) patients. In cell dilution experiments, the analytical sensitivity of this reagent was equal to that of the X chromosome and Y chromosome alpha-satellite probes. These optimized probes should facilitate the quantitative assessment and study of MRD in t(8;21) AML.

ETO and AML1 phosphoproteins are expressed in CD34+ hematopoietic progenitors: implications for t(8;21) leukemogenesis and monitoring residual disease.

To study acute myelogenous leukemia 1 (AML1) transcription factor, ETO protein, and t(8;21) AML chimeric AML1/ ETO protein in normal hematopoiesis and in leukemia, we raised rabbit antisera to a bacterially expressed polypeptide containing amino acid residues 1 to 220 of ETO and to synthetic peptides extending from residues 528 to 548 of ETO and 32 to 50 of AML1. The latter was selected to have little chance of cross-reactivity with other members of the PEBP2 alpha family. With affinity-purified reagents, we observed immunofluorescent staining for both AML1 and ETO in the nucleus of HEL, K562, and Kasumi-1 leukemic cell lines, the last from a t(8;21) AML. Biochemical analysis confirmed specificity of the antibodies and the nuclear localization of the antigens, the latter being exclusive for AML1 and primary for ETO. Immunoprecipitations of metabolically labeled 32P-proteins from Kasumi-1 cells show that AML1 and ETO are phosphorylated on serine and threonine. Investigations with normal bone marrow reveal AML1 and ETO are coexpressed in megakaryocytes and that each is expressed in a portion of the approximately 10-microns-diameter cells residing there. Using a CD34+ enriched population mobilized to peripheral blood, we found AML1 and, unexpectedly, ETO present in these cells. Because of this, we conclude that the expression of ETO in hematopoietic cells is not by itself leukemogenic. Also, because ETO would not be exclusively expressed as part of chimeric AML1/ETO in leukemic patients, its presence cannot be used to monitor t(8;21) AML residual disease.