bluuebunny/crossref_metadata_2025 huggingface dataset:
QSAR Study of Aromatic Organochalcogens with Glutathione Peroxidase – like Antioxidant Activity
Authors: Nikolic Katarina M.
Published: September 2006

The molecular orbital energies and atomic Electron Densities (ED) of compounds that mimic the action of Glutathione Peroxidase (GPx), such as derivatives of α‐(phenylselenenyl) keton (PhSeR1) and aromatic organochalcogens [YPh(X)1–2PhY], were calculated by ab initio Hartree‐Fock/3‐21G (d)gas basis set. Single and multiple linear regression models for two types of aromatic chalcogens were obtained with R2>0.75 and $\rm{ q_{{\rm{pre}}}^2 }$>0.63. For the α‐(phenylselenenyl) keton and derivatives that react with Glutathione (GSH) via mixed selenenyl‐sulfide compounds (RSeSG), a high correlation was obtained between the calculated LUMO (PhSeR1) energies and experimentally measured GPx like antioxidant activities. Thus, it is recommended to use the LUMO (PhSeR1) energies of novel derivatives (PhSeR1) of α‐(phenylselenenyl) keton in the prediction of GPx like catalytic antioxidant activities. For the aromatic organochalcogens [YPh(X)1–2PhY] that react with GSH mainly via chalcogen‐oxide intermediates, the Electrochemical Oxidation Potential (Epa) values on the glassy carbon electrode in aqueous media, the HOMO [YPh(X)1–2PhY] energies, and the ED on chalcogens [ED(X)] were selected as good predictors of GPx like catalytic antioxidant activities.
Neural Network Based QSPR Study for Predicting pKa of Phenols in Different Solvents
Authors: Jover Jesús , Bosque Ramón , Sales Joaquim
Published: September 2006

Computational Neural Network (CNN) based QSPR methodology is applied to a multicomponent system: the prediction of pKa of phenols in different solvents. The system is composed of 94 phenols, 10 solvents, and 276 experimental pKa values. The phenols are characterized by the habitual molecular descriptors, while the solvents are described by a number of physical properties and by several parameters of the most used multiparametric polarity solvent scales. The proposed model, non‐linearly derived, contains seven descriptors; five of them belong to the solutes and the other two to the solvents. Good results are obtained with a Root‐Mean‐Square Error (RMSE) and correlation coefficients (R2) of 0.71 (0.982), 0.83 (0.977), and 0.95 (0.975) for the training, prediction, and cross validation sets, respectively. The robustness of the model is also in accord with the statistical results obtained from particular subsets of phenols with and without ortho‐substituents and those obtained from the subsets of values of pKa determined in protic or in aprotic solvents and also in each solvent. The descriptors of the model encode information that reflects characteristics of the molecules of the solutes and the solvents clearly related to the interactions acting in the dissociation process.
A comparison of adaptive allocation rules for group‐sequential binary response clinical trials
Authors: Morgan Caroline C. , Stephen Coad D.
Published: September 2006

In clinical trials to compare two or more treatments with dichotomous responses, group‐sequential designs may reduce the total number of patients involved in the trial and response‐adaptive designs may result in fewer patients being assigned to the inferior treatments. In this paper, we combine group‐sequential and response‐adaptive designs, extending recent work on sample size re‐estimation in trials to compare two treatments with normally distributed responses, to analogous binary response trials. We consider the use of two parameters of interest in the group‐sequential design, the log odds ratio and the simple difference between the probabilities of success. In terms of the adaptive sampling rules, we study two urn models, the drop‐the‐loser rule and the randomized Pólya urn rule, and compare their properties with those of two sequential maximum likelihood estimation rules, which minimize the expected number of treatment failures. We investigate two ways in which adaptive urn designs can be used in conjunction with group‐sequential designs. The first method updates the urn at each interim analysis and the second method continually updates the urn after each patient response, assuming immediate patient responses. Our simulation results show that the group‐sequential design, which uses the drop‐the‐loser rule, applied fully sequentially, is the most effective method for reducing the expected number of treatment failures and the average sample number, whilst still maintaining the nominal error rates, over a range of success probabilities. Copyright © 2006 John Wiley & Sons, Ltd.
Quantifying the treatment effect explained by markers in the presence of measurement error
Authors: Sarkar Somnath , Qu Yongming
Published: September 2006

Surrogate markers or intermediate markers are important in identifying subjects with high risk of a serious disease or for monitoring disease progression of a subject on treatment. Quantifying the proportion of treatment effect (PTE) explained by markers has been studied extensively. Due to reasons such as biological variation, limited machine precision, etc. markers are generally measured with error. The estimated PTE ignoring the measurement error could be biased, which may lead to incorrect conclusions. In this article, we adjust for the measurement error using regression calibration to construct a less biased estimator of excess relative odds, a quantity to measure the treatment effect explained by markers. The method is applied to data from a clinical study in osteoporosis. Copyright © 2006 John Wiley & Sons, Ltd.
Evidence‐based sample size calculations based upon updated meta‐analysis
Authors: Sutton Alexander J. , Cooper Nicola J. , Jones David R. , Lambert Paul C. , Thompson John R. , Abrams Keith R.
Published: September 2006

Meta‐analyses of randomized controlled trials (RCTs) provide the highest level of evidence regarding the effectiveness of interventions and as such underpin much of evidence‐based medicine. Despite this, meta‐analyses are usually produced as observational by‐products of the existing literature, with no formal consideration of future meta‐analyses when individual trials are being designed.

Basing the sample size of a new trial on the results of an updated meta‐analysis which will include it, may sometimes make more sense than powering the trial in isolation. A framework for sample size calculation for a future RCT based on the results of a meta‐analysis of the existing evidence is presented.

Both fixed and random effect approaches are explored through an example. Bayesian Markov Chain Monte Carlo simulation modelling is used for the random effects model since it has computational advantages over the classical approach. Several criteria on which to base inference and hence power are considered. The prior expectation of the power is averaged over the prior distribution for the unknown true treatment effect. An extension to the framework allowing for consideration of the design for a series of new trials is also presented.

Results suggest that power can be highly dependent on the statistical model used to meta‐analyse the data and even very large studies may have little impact on a meta‐analysis when there is considerable between study heterogeneity. This raises issues regarding the appropriateness of the use of random effect models when designing and drawing inferences across a series of studies. Copyright © 2006 John Wiley & Sons, Ltd.
Ordered Assembly of α‐Quinquethiophene on a Copper Oxide Nanotemplate
Authors: Cicoira Fabio , Miwa Jill A. , Melucci Manuela , Barbarella Giovanna , Rosei Federico
Published: September 2006

The organic semiconductor α‐quinquethiophene (T5) is used as the active layer in organic field‐effect transistors. We have investigated the adsorption of T5 on the (110) surface of copper and on the CuO nanotemplate formed by the high‐temperature exposure of Cu(110) to molecular oxygen. The results were obtained with high‐resolution scanning tunneling microscopy (STM) under ultra‐high‐vacuum (UHV) conditions. The adsorption of T5 on copper is an important model system because it mimics the active‐layer–electrode interface in organic devices. The molecules were observed to adsorb onto both the pristine Cu(110) surface and the CuO nanotemplate, showing a greater affinity for the pristine copper surface. Surprisingly, however, the T5 molecules assembled with a much higher degree of long‐range order on the oxygen‐passivated portion of the surface.
Observational Assessment of Surgical Teamwork: A Feasibility Study
Authors: Undre Shabnam , Healey Andrew N. , Darzi Ara , Vincent Charles A.
Published: September 2006

Background

Teamwork is fundamental to effective surgery, yet there are currently no measures of teamwork to guide training, evaluate team interventions or assess the impact of teamwork on outcomes. We report the first steps in the development of an observational assessment of teamwork and preliminary findings.

Method

We observed 50 operations in general surgery from a single operating theater using a measure of teamwork specifically developed for use in the operating theater. The OTAS (Observational Teamwork Assessment for Surgery) comprises a procedural task checklist centered on the patient, equipment and communications tasks and ratings on team behavior constructs, namely: communication, co‐operation, co‐ordination, shared‐leadership and monitoring.

Results

Ratings of overall team performance were reasonably high, though variable, but there was evidence that clinically significant steps were being missed which at the very least eroded safety margins. There was, for instance, a frequent failure to check both surgical and anesthetic equipment and a failure to confirm the procedure verbally, patient notes were missing in about one‐eighth of the cases and delays or changes occurred in over two‐thirds of the cases.

Conclusions

This study takes an initial step towards developing measures of team performance in surgery that are defined in relation to tasks and behaviors of the team. The observational method of assessment is feasible and can provide a wealth of potentially valuable research data. However, for these measures to be used for formal assessment, more research is needed to make them robust and standardized.
Distinct Recurrence Pattern and Outcome of Adenocarcinoma of the Gastric Cardia in Comparison with Carcinoma of Other Regions of the Stomach
Authors: Saito Hiroaki , Fukumoto Youji , Osaki Tomohiro , Fukuda Kenji , Tatebe Shigeru , Tsujitani Shunichi , Ikeguchi Masahide
Published: September 2006

Background

Carcinoma arising in the cardioesophageal junction is a distinct clinical entity compared with tumors located in other regions of the stomach. The prognosis for adenocarcinoma of the upper stomach is considered to be relatively poorer than carcinomas of the more distal stomach. We have therefore investigated patients with carcinoma of the gastric cardia in order to evaluate the underlying cause of this poor prognosis.

Materials and Methods

Clinicopathologic features and postoperative prognosis of 101 patients with carcinoma of the cardia were evaluated and compared with findings on 1884 patients with tumors in other regions of the stomach.

Results

Tumors of the cardia had a mean size of 6.8 cm, which was significantly larger than the mean size of 5.9 cm for tumors found in the middle‐ and lower third of the stomach. The incidence of serosal invasion, lymph node metastasis, and lymphatic and blood vessel invasion was higher in association with adenocarcinoma of the cardia than with adenocarcinoma in remaining parts of the stomach. In the analysis of patients who had undergone curative resection, the 5‐year survival rates were 61.6, 79.1, and 82.6% in patients with carcinoma of the cardia, upper one‐third, and remaining middle‐ and lower one‐third of the stomach, respectively, and the differences were statistically significant. Multivariate analysis indicated that adenocarcinoma of the gastric cardia is an independent prognostic factor. With regard to the site of recurrence, both lymph node and hematogenous recurrence were observed more frequently in the cardia than in the remaining parts of the stomach.

Conclusions

Our data indicate that the prognosis of patients with adenocarcinoma of the gastric cardia is extremely poor. To improve their prognosis, new treatments in addition to gastrectomy with extensive lymph node dissection are needed.
Assessment of Nutritional Status and Prediction of Postoperative Liver Function from Serum Apolioprotein A‐1 Levels with Hepatectomy
Authors: Katsuramaki Tadashi , Mizuguchi Toru , Kawamoto Masaki , Yamaguchi Kouji , Meguro Makoto , Nagayama Minoru , Nobuoka Takayuki , Kimura Yasutoshi , Furuhata Tomohisa , Hirata Koichi
Published: September 2006

Background

We investigated the usefulness of apolipoprotein A‐1 (apoA) as an indicator of nutritional status, and the correlation of the preoperative apoA level with changes in postoperative liver function following hepatectomy.

Methods

One hundred patients underwent hepatectomy. Serum levels of apoA, prealbumin (prealb), retinol‐binding protein (RBP), lectin‐cholesterol acyltransferase (LCAT), hyarulonate (HA), indocyanine green dye retention at 15 minutes (ICG), and the receptor index of Tc‐GSA scintigraphy (LHL15) were measured at preoperation and on postoperative days (POD) 7 and 14. Partial resection was carried out in 62 cases, segmentectomy in nine cases, and bisegmentectomy in 29 cases. Co‐existent liver conditions were normal liver (NL) in 43 cases, chronic hepatitis (CH) in 29 cases, and liver cirrhosis (LC) in 28 cases.

Results

In most cases the serum apoA level had decreased on POD 7, and recovered on POD 14. There were no significant differences in the changes of apoA between the individual operative procedures. Although preoperative apoA had almost the same value in the NL, CH, and LC cases, apoA in LC cases on POD 14 was the lowest of all cases. The apoA level showed significant correlations with prealb, LCAT, and HA on POD 14. All cases were divided into two groups (group N: apoA over 91 mg/dl; group L: apoA under 90 mg/dl) based on the preoperative serum apoA level. On POD 14, the ICG, LHL15, and HA of group L were significantly deteriorated compared with those of group L.

Conclusion

The serum level of apoA reflects the changes in hepatic protein synthetic ability after hepatectomy; therefore, it may be possible to estimate recovery of nutritional status after hepatectomy from serum apoA. Moreover, we can predict postoperative deterioration of liver function from the preoperative apoA level.
Quality of Life Following Laparoscopic Anterior 90° Versus Nissen Fundoplication: Results from a Multicenter Randomized Trial
Authors: Woodcock Sean A. , Watson David I. , Lally Carolyn , Archer Stephen , Bessell Justin R. , Booth Michael , Cade Richard , Cullingford Graham L. , Devitt Peter G. , Fletcher David R. , Hurley James , Jamieson Glyn G. , Kiroff George , Martin Christopher J. , Martin Ian J. G. , Nathanson Leslie K. , Windsor John A.
Published: September 2006

Background

The short‐term clinical outcomes from a multicenter prospective randomized trial of laparoscopic Nissen versus anterior 90° partial fundoplication have been reported previously. These demonstrated a high level of satisfaction with the overall outcome following anterior 90° fundoplication. However, the results of postoperative objective tests and specific clinical symptoms are not always consistent with an individual patient’s functional status and general well being following surgery, and quality of life (QOL) is also an important outcome to consider following surgery for reflux. Hence, QOL information was collected in this trial to investigate the hypothesis: improvements in QOL following laparoscopic antireflux surgery are greater after anterior 90° partial fundoplication than after Nissen fundoplication.

Methods

Patients undergoing a laparoscopic fundoplication for gastro‐esophageal reflux at one of nine university teaching hospitals in six major cities in Australia and New Zealand were randomized to undergo either laparoscopic Nissen or anterior 90° partial fundoplication. Quality of life before and after surgery was assessed using validated questionnaires – the Short Form 36 general health questionnaire (SF36) and an Illness Behavior Questionnaire (IBQ). Patients were asked to complete these questionnaires preoperatively and at 3, 6, 12 and 24 months postoperatively.

Results

One hundred and twelve patients were randomized to undergo a Nissen fundoplication (52) or a 90° anterior fundoplication (60). Patients who underwent anterior fundoplication reported significant improvements in eight of the nine SF36 scales compared to four of the nine following a Nissen fundoplication. The majority of these improvements occurred early in the postoperative period. With respect to the illness behavior data, there were no significant differences between the two procedures. Both groups had a significant improvement in disease conviction scores at all time points compared to their preoperative scores.

Conclusions

Patients undergoing laparoscopic anterior 90° partial fundoplication reported more QOL improvements in the early postoperative period than patients undergoing a Nissen fundoplication. However, the QOL outcome for both procedures was similar at later follow‐up.
Benefits of a Synbiotic Formula (Synbiotic 2000Forte®) in Critically Ill Trauma Patients: Early Results of a Randomized Controlled Trial
Authors: Kotzampassi Katerina , Giamarellos‐Bourboulis Evagellos J. , Voudouris Antonios , Kazamias Pantelis , Eleftheriadis Efthimios
Published: September 2006

Background

Since probiotics are considered to exert beneficial health effects by enhancing the host’s immune response, we investigated the benefits of a synbiotics treatment on the rate of infections, systemic inflammatory response syndrome (SIRS), severe sepsis, and mortality in critically ill, mechanically ventilated, multiple trauma patients. Length of stay in the intensive care unit (ICU) and number of days under mechanical ventilation were also evaluated.

Method

Sixty‐five patients were randomized to receive once daily for 15 days a synbiotic formula (Synbiotic 2000Forte, Medipharm, Sweden) or maltodextrin as placebo. The synbiotic preparation consisted of a combination of four probiotics (1011 CFU each):Pediococcus pentosaceus 5–33:3, Leuconostocmesenteroides 32–77:1, L.paracasei ssp.paracasei 19; and L. plantarum 2,362; and inulin, oat bran, pectin, and resistant starch as prebiotics. Infections, septic complications, mortality, days under ventilatory support, and days of stay in ICU were recorded.

Results

Synbiotic‐treated patients exhibited a significantly reduced rate of infections (P = 0.01), SIRS, severe sepsis (P = 0.02), and mortality. Days of stay in the ICU (P = 0.01) and days under mechanical ventilation were also significantly reduced in relation to placebo (P = 0.001).

Conclusion

The administration of this synbiotic formula in critically ill, mechanically ventilated, multiple trauma patients seems to exert beneficial effects in respect to infection and sepsis rates and to improve the patient’s response, thus reducing the duration of ventilatory support and intensive care treatment.
Prophylactic Antibiotics in Chest Trauma: A Meta‐analysis of High‐quality Studies
Authors: Sanabria Alvaro , Valdivieso Eduardo , Gomez Gabriel , Echeverry Gabriel
Published: September 2006

Background

Use of antibiotics in patients with isolated chest trauma is controversial. Available studies offer contradictory results because of small sample sizes. However, information provided by recent randomized controlled trials (RCT) included in a systematic review and meta‐analysis could help solve the controversy. We performed a systematic review using high‐quality information related to the use of antibiotics in patients with a chest tube.

Methods

We developed a systematic review to evaluate the effectiveness of prophylactic antibiotics in chest‐trauma patients. Studies included were class I RCT comparing prophylactic antibiotics versus placebo in patients with isolated chest trauma. Main outcomes were posttraumatic empyema and pneumonia.

Results

Five Class I studies were selected. There were statistically significant differences regarding the frequency of posttraumatic empyema (RR 0.19) and pneumonia (RR 0.44) in favor of the use of prophylactic antibiotics when compared with placebo.

Conclusions

The use of prophylactic antibiotics in patients with chest trauma decreases the incidence of posttraumatic empyema and pneumonia.
Management of Right Colon Diverticulitis: A 10‐Year Experience
Authors: Yang Horng‐Ren , Huang Huai‐Hsu , Wang Yu‐Chun , Hsieh Chi‐Hsun , Chung Ping‐Kuei , Jeng Long‐Bin , Chen Ray‐Jade
Published: September 2006

Background

Controversies abound as regards the optimal treatment for patients with diverticulitis of the right colon.

Methods

This is a retrospective review of 113 patients with a diagnosis of right colonic diverticulitis who received treatment at the China Medical University Hospital from July 1994 to June 2004.

Results

Medical therapy was undertaken in 56 patients diagnosed preoperatively with uncomplicated diverticulitis. All but one patient was successfully treated with bowel rest and antibiotics. Of the 51 patients with a preoperative diagnosis of acute appendicitis, 32 received appendectomy along with postoperative antibiotic therapy, 8 received diverticulectomy in addition to appendectomy, and 11 received colectomy. In all, 17 patients required right hemicolectomy or ileocecal resection due to diverticulitis‐related complications or suspected malignancy. Of the 87 (56−1+32) patients who responded to conservative treatment, 11 developed recurrent diverticulitis. All 11 patients were successfully treated with medical therapy, and 2 subsequently received elective right hemicolectomy. Of the 9 patients who received medical treatment alone at the second attack, 2 suffered a third attack. Both were successfully managed with medical therapy.

Conclusions

For uncomplicated diverticulitis of the right colon diagnosed preoperatively, antibiotic therapy with bowel rest is an effective treatment. Once it is encountered during surgery for presumed acute appendicitis, a conservative approach involving prophylactic appendectomy and postoperative antibiotics is recommended. For patients with recurrent diseases, medical treatment is still safe and efficient. Colectomy is indicated when complications occur or when malignancy is strongly suspected.
Effect of Prevailing Local Treatment Options of Breast Cancer on Survival Outside Controlled Clinical Trials: Experience of a Specialist Breast Unit in North India
Authors: Tewari Mallika , Pradhan S. , Kumar M. , Shukla H. S.
Published: September 2006

Background

This study aimed at analyzing different treatments of breast cancer (BC) prevalent in the region, their effect on patients’ survival, and discusses the most suitable method within available resources.

Methods

The study was set up at a tertiary care hospital in north India. We retrospectively reviewed data of 473 female BC patients who attended the departments of Surgical Oncology and Radiotherapy from January 1997 to December 1999. Patients with cTNM stage IV and inoperable stage III were included; those who defaulted or were lost to follow‐up were excluded. Out of 473 patients, 372 were selected. The selected patients were divided into groups on the basis of place and type of local treatment they received: (1) local excision only, (2) standard breast conservation therapy (BCT), (3) total mastectomy (TM) + axillary lymph node dissection + radiotherapy (RT), and (4) modified radical mastectomy (MRM) + RT. Data regarding recurrence and survival were analyzed in December 2005. Minimum follow‐up was 6 years.

Results

Overall recurrence rates were significantly higher in patients operated elsewhere (P <0.0001). Of 194 operated at our Breast Unit, 25 (14.6%) of 171 MRM patients and none of 23 BCT had recurrence. Of 178 patients operated elsewhere, 44 (100%), 6 (42.9%), 41 (41%), and 8 (40%) developed recurrence in groups 1, 2, 3, and 4 respectively. Overall survival was significantly better in patients with MRM at our unit versus TM outside (93.6% vs. 80%).

Conclusions

Several types of treatment from improper local excision alone, BCT, TM, to a carefully done MRM are prevalent here. Properly done, MRM yields significant local control with survival benefit and appears to remain the gold standard in management of our BC patients.
Who Will Care for Iraq’s Wounded Warriors? Health Policy and National Security
Authors: Bowersox Jon C. , Al‐Ainachi Shakir
Published: September 2006

Introduction

Since 2003, Iraq has struggled to build a single national health system administered by the Iraqi Ministry of Health, but politics, lack of leadership, and a cultural bias against treating soldiers in civilian hospitals have hindered access to care for members of Iraq’s armed forces who are wounded in combat.

Methods

U.S. surgeons are providing trauma care for Iraqi soldiers in American field hospitals, with more than 80% of hospital bed days occupied by Iraqis. At the same time, Iraqi hospitals have been treating the many civilian casualties of violence, and the Ministry of Health has greatly improved its emergency response and management capabilities over the past year.

Results

Ministry of Health hospitals have adequate surgical capabilities and bed capacity to care for both civilian and security forces casualties. Faltering attempts to develop a national health policy that provides comprehensive care for Iraqi Security Forces will jeopardize Iraq’s ability to assume responsibilities for the country’s national defense, and could delay the withdrawal of Coalition military forces from Iraq.

Conclusions

It is imperative that leadership of the new government of Iraq and the international surgical community strongly endorse the implementation of a single health care system for all Iraqis.
Hepatectomy for Colorectal Liver Metastases with Macroscopic Intrabiliary Tumor Growth
Authors: Sugiura Teiichi , Nagino Masato , Oda Koji , Ebata Tomoki , Nishio Hideki , Arai Toshiyuki , Nimura Yuji
Published: September 2006

Objectives

We set out to clarify the clinicopathologic characteristics of colorectal liver metastases with macroscopic intrabiliary tumor growth and to determine optimal surgical management.

Methods

Over 15 years, 6 of 103 patients undergoing hepatectomy for colorectal liver metastases had macroscopic intrabiliary tumor growth and were analyzed retrospectively.

Results

We performed 11 operations for the 6 patients, consisting of 10 hepatectomies (including 1 hepatopancreatoduodenectomy) and 1 pancreatoduodenectomy. Three patients survived more than 5 years: 1 died of pulmonary emphysema with no sign of recurrence 101 months after initial hepatectomy; the 2 others were alive with no sign of recurrence at 74 and 145 months after initial hepatectomy. Median survival time of all 6 patients was 87.5 months. Histologically, intrabiliary tumor growth had two components: intraluminal and intraepithelial extension. In the proximal direction, distance between these two components ranged from 4–10 mm.

Conclusion

Aggressive surgical treatment can improve chances of long‐term survival for patients with macroscopic intrabiliary growth of colorectal liver metastasis. Although nonanatomic limited resection is a common procedure for colorectal liver metastasis, anatomic hepatobiliary resection is recommended.
Cultivating Systemic Capacity: The Rhode Island Tobacco Control Enhancement Project
Authors: Florin Paul , Celebucki Carolyn , Stevenson John , Mena Jasmine , Salago Dawn , White Andrew , Harvey Betty , Dougal Marianela
Published: September 2006

This paper describes the Rhode Island Tobacco Control Enhancement Project (TCEP), a state‐university‐community technical assistance system. TCEP was developed under the auspices of the Rhode Island Department of Health's Tobacco Control program and was designed to build capacity among nine community‐based organizations to mount comprehensive tobacco control interventions in five diverse communities within the state. This paper: (1) provides a description of community mobilization; (2) presents a logic model for planning and decision making used by state‐university‐community partners; (3) describes training, technical assistance services and implementation; and, (4) describes the evaluation and program improvement activities used to support on‐going project development.
A Record of Holocene Climate Change from Lake Geochemical Analyses in Southeastern Arabia
Authors: Parker Adrian G. , Goudie Andrew S. , Stokes Stephen , White Kevin , Hodson Martin J. , Manning Michelle , Kennet Derek
Published: September 2006

Lacustrine sediments from southeastern Arabia reveal variations in lake level corresponding to changes in the strength and duration of Indian Ocean Monsoon (IOM) summer rainfall and winter cyclonic rainfall. The late glacial/Holocene transition of the region was characterised by the development of mega-linear dunes. These dunes became stabilised and vegetated during the early Holocene and interdunal lakes formed in response to the incursion of the IOM at approximately 8500 cal yr BP with the development of C3 dominated savanna grasslands. The IOM weakened ca. 6000 cal yr BP with the onset of regional aridity, aeolian sedimentation and dune reactivation and accretion. Despite this reduction in precipitation, the lake was maintained by winter dominated rainfall. There was a shift to drier adapted C4 grasslands across the dune field. Lake sediment geochemical analyses record precipitation minima at 8200, 5000 and 4200 cal yr BP that coincide with Bond events in the North Atlantic. A number of these events correspond with changes in cultural periods, suggesting that climate was a key mechanism affecting human occupation and exploitation of this region.
Biological activity of bovine milk on proliferation of human intestinal cells
Authors: Purup Stig , Vestergaard Mogens , O Pedersen Lone , Sejrsen Kris
Published: September 2006

To evaluate the bioactivity of bovine milk from different stages of lactation on human intestinal tissue, a human fetal small intestinal cell line was used as a model system. Milk samples representing six stages of lactation: days 1, 2–3, 6–7 and weeks 12 and 24 after parturition, 1 week before drying off, and milk-like secretion from two stages of the dry period: 7 weeks and 3–4 weeks before expected calving, were collected from 64 Holstein Friesian cows. The whey fraction of the milk or milk-like secretion was added to the culture medium in concentrations ranging from 0·078% to 10%. The growth-promoting activity of whey was measured by determining the incorporation of [3H]thymidine into DNA for the last 24 h of the culture period. Whey fractions from all six stages of lactation stimulated growth of intestinal cells. The growth-promoting activity of colostrum or milk significantly decreased within the first week after calving. The growth-promoting activity in mature milk increased gradually during lactation to reach a level significantly higher than that obtained with colostrum. The growth-promoting activity of whey from milk-like secretion collected after drying off was lower than that of colostrum. Whey from different stages of lactation contained significantly different concentrations of TGF-β1 (0·5–27 ng/ml) and TGF-β2 (12–1219 ng/ml). However, neither the differences in TGF-β1 and TGF-β2, nor the differences in IGF-I and IGF-binding proteins could fully explain the differences in growth-promoting activity of colostrums or milk from different stages of lactation, suggesting that other factors were also involved. The present study showed that bovine milk contained a number of biologically active components that affected growth and development of human intestinal tissue. The results showed that the growth-promoting activity of colostrum and milk was dependent on the stage of lactation in accordance with previous results obtained with mammary epithelial cells. The changes in growth-promoting activity with stage of lactation were probably related to changes in concentrations of several growth factors.
Effect of a metabolically created systemic acidosis on calcium homeostasis and the diurnal variation in urine pH in the non-lactating pregnant dairy cow
Authors: Roche John R , Dalley Dawn E , O'Mara Frank P
Published: September 2006

Reducing the dietary cation-anion difference (DCAD) has been shown to be an effective means of preventing parturient paresis in confinement systems where cows are offered a total mixed ration containing DCAD-reducing mineral compounds (anionic salts). Such a supplementation strategy is not possible in cows being group fed forages precalving, and little is known about the effect of supplementing these cows with large amounts of anionic salts twice daily.

Eight non-lactating, pregnant Holstein-Friesian cows were allocated to two levels of DCAD (−20 and +18 meq/100 g DM) for 24 d, with an intensive Ca balance undertaken in metabolism stalls following a 2-week acclimatization to diet. The basal diet was 3 kg DM of crushed barley and 7 kg DM of pasture-hay. Urine and faeces were collected separately, weighed daily for 5 d and analysed for Ca content. Urinary Ca, creatinine and hydroxyproline concentration and plasma Ca concentration were determined during the period of the balance study. The diurnal pattern in urine and rumen pH was determined over 2 d. Decreasing DCAD reduced (P<0·001) the pH of urine, and increased (P<0·05) Ca absorption. Plasma Ca concentration was not affected by DCAD, and DCAD did not affect the output of urinary hydroxyproline, a marker of bone resorption. Twice-daily supplementation of anionic salts was sufficient to reduce the pH of blood and increase gastrointestinal Ca absorption. There was no diurnal variation in the pH of urine, suggesting that time of sampling to determine efficacy of DCAD in reducing systemic pH was not important.
Natural and recombinant bovine somatotropin: immunodetection with a sandwich ELISA
Authors: Castigliego Lorenzo , Iannone Giorgio , Grifoni Goffredo , Rosati Remo , Gianfaldoni Daniela , Guidi Alessandra
Published: September 2006

Bovine Somatotropin (bST) is a peptide hormone secreted by the anterior pituitary gland and its recombinant form (rbST) is used for artificially boosting milk yield in cows. Identification of rbST is difficult in that there is little difference from the pituitary bST (pbST). In this work, we further studied the possibility of immunologically discriminating between rbST and pbST. With this purpose, we produced mouse monoclonal antibodies using, as antigen, a peptide mimicking the N-terminus of rbST from Monsanto (rbST-M) conjugated to keyhole limpet haemocyanin (KLH) and polyclonal antibodies in rabbits immunized with the whole bST or rbST-M. Hence, we developed a sandwich ELISA with the obtained antibodies for detection and quantification of bST in serum and compared its performance on the two worldwide commercialized rbSTs: rbST-M and rbST from LG Life Science (rbST-LG). The lowest detection limit of the assay was 0·05 ng/ml for rbST-M, 0·10 ng/ml for rbST-LG and 0·15 ng/ml for pbST. Furthermore, the assay showed the capability to amplify the signal in the presence of rbSTs, recognizing more efficiently rbST-M and rbST-LG than pbST (ECn pbST/ECn rbST: 3 and 1·6 respectively). Its employment for measuring bST levels in sera from bovines administered with rbST LG allowed us to detect exceptional values due to the treatment itself and probably further increased as a consequence of the higher affinity for rbSTs of our monoclonal antibody.
Effects of melatonin on the yield and composition of milk from grazing dairy cows in New Zealand
Authors: Auldist Martin J , Turner Sally-Anne , McMahon Chris D , Prosser Colin G
Published: September 2006

The aim was to determine whether administration of melatonin would alter the yield and composition of milk from grazing dairy cows in summer. Twelve sets of spring-calving identical twin Friesian cows were used in the experiment. In late-November (late spring), one twin from each set was given slow-release melatonin implants behind the ears (108 mg melatonin/cow). Two further implantations occurred at 4-weekly intervals to maintain increased circulating concentrations of melatonin for 12 weeks. The other twin served as a control. Milk yield and composition were measured twice prior to treatment and then four times over the following 12 weeks. Concentrations of melatonin, prolactin and insulin-like growth factor 1 (IGF-1) were measured in blood plasma twice before treatment and then either seven (melatonin and prolactin) or three (IGF-1) further times during the experiment. Management procedures for all cows were similar and cows grazed a daily pasture allowance of approximately 30 kg DM/cow as their sole feed source. In melatonin-treated cows there was a decrease in mean concentrations of prolactin in plasma, but concentrations of IGF-1 did not change. Melatonin reduced milk yield by 6 weeks after treatment and by the end of the 12-week experimental period milk yield in melatonin-treated cows had fallen by 23%. Melatonin also reduced concentrations of lactose in milk, but increased concentrations of fat, protein and casein, changes that were broadly similar to those that occur in late lactation in seasonally calving dairy cows. Thus, the results suggest that some of the variation in the volume and quality of milk throughout the season in New Zealand dairy systems may be due to changes in photoperiod mediated by increased concentrations of plasma melatonin in association with decreased concentrations of plasma prolactin.
Associations between somatic cell counts at calving or prior to drying-off and clinical mastitis in the remaining or subsequent lactation
Authors: Whist Anne Cathrine , Østerås Olav
Published: September 2006

Data from 350 herds enrolled in the Norwegian Dairy Herd Recording System (NDHRS) were used to investigate the associations between the first two cow-milk somatic cell counts (SCC) test-days’ results after calving or the three last SCC test-days prior to drying off in the first lactation and the hazard ratio (HR) of clinical mastitis (CM) during the remaining first or the subsequent second lactation respectively. Altogether, 9519 first lactations and 6046 second lactations were included. Cox regression analyses adjusted for herd frailty effect were used. In the first lactation, SCC>40000 cells/ml on the first or second test-day was significantly associated with an increased risk of a CM event in the remaining first lactation. HR, compared with 10000 cells/ml, increased from 1·6 (1·4) for SCC of 40000–60000 cells/ml to 6·9 (4·2) for SCC >800000 cells/ml, when using the first (second) SCC test-day in the first lactation. Cows with a geometric mean of the three last SCC test-days between 50000 and 100000 cells/ml and between 401000 and 800000 cells/ml in the first lactation had HR of CM during the second lactation of 1·3 and 2·8 respectively compared with a reference group of 10000–20000 cells/ml. If a CM episode in the first lactation occurred, the HR for having a CM event during the second lactation was 1·5. There was a significant frailty effect which disappeared if the incidence rate of CM at herd level was included in the model.
Associations between lameness and production, feeding and milking attendance of Holstein cows milked with an automatic milking system
Authors: Bach Alex , Dinarés Martí , Devant Maria , Carré Xavier
Published: September 2006

A longitudinal study involving 73 primiparous (PP) and 47 multiparous (MP) Holstein cows was conducted over an 8-month period to assess the associations between locomotion score (LCS) and milk production, dry matter intake (DMI), feeding behaviour, and number of visits to an automatic milking system (AMS). Twice weekly, all cows were locomotion scored (scale 1–5) by the same observer. Individual eating behaviour and individual feed consumption at each cow visit to the feed troughs, individual milk production, the time of milking, and the number of milkings for each cow were recorded for the day of locomotion scoring and the day before and after. Dependent variables, such as milk yield, DMI, etc. were modelled using a mixed-effects model with parity, LCS, days in milk (DIM), the exponential of −0·05 DIM, and the interaction between parity and LCS, as fixed effects and random intercepts and random slopes for the linear and the exponential of −0·05DIM effects within cow. LCS did not affect time of attendance at feed troughs, but affected the location that cows occupied in the feed troughs. The time devoted to eating and DMI decreased with increasing LCS. Milk production decreased with LCS>3. The number of daily visits to the AMS also decreased with increasing LCS. The cows with high LCS were fetched more often than the cows with low LCS. Overall, PP cows were more sensitive to the effects of increasing LCS than were MP cows. The decrease in milk production observed with increasing LCS seemed to be affected similarly by the decrease in DMI and by the decrease in number of daily visits to the AMS. A further economic loss generated by lame cows with AMS will be associated with the additional labour needed to fetch them.
GATA factors in vertebrate heart development and disease
Authors: Brewer Alison , Pizzey John
Published: September 2006

Vertebrate heart formation is dependent upon complex hierarchical gene regulatory networks, which effect both the specification and differentiation of cardiomyocytes and subsequently cardiac morphogenesis. GATA-4, -5 and -6 comprise an evolutionarily conserved subfamily of transcription factors, which are expressed within the precardiac mesoderm from early stages in its specification and continue to be expressed within the adult heart. We review here the functional roles of individual GATA transcription factors in cardiac development, normal homeostasis and disease. We also review the cellular mechanisms employed to regulate the expression and downstream targets of the different GATA factors.
Enantioselective Synthesis of l‐Homophenylalanine by Whole Cells of Recombinant Escherichia coli Expressing l‐Aminoacylase and N‐Acylamino Acid Racemase Genes from Deinococcus radiodurans BCRC12827
Authors: Hsu Shih‐Kuang , Lo Hsueh‐Hsia , Kao Chao‐Hung , Lee Dong‐Sheng , Hsu Wen‐Hwei
Published: September 2006

l‐Homophenylalanine (l‐HPA) is a chiral unnatural amino acid used in the synthesis of angiotensin converting enzyme inhibitors and many pharmaceuticals. To develop a bioconversion process with dynamic resolution of N‐acylamino acids for the l‐HPA production, N‐acylamino acid racemase (NAAAR) and l‐aminoacylase (LAA) genes were cloned from Deinococcus radiodurans BCRC12827 and expressed in Escherichia coli XLIBlue. The recombinant enzymes were purified by nickel‐chelate chromatography, and their biochemical properties were determined. The NAAAR had high racemization activity toward chiral N‐acetyl‐homophenylalanine (NAc‐HPA). The LAA exhibited strict l‐enantioselection to hydrolyze the NAc‐l‐HPA. A stirred glass vessel containing transformed E. coli cells expressing D. radiodurans NAAAR and LAA was used for the conversion of NAc‐d‐HPA to l‐HPA. Unbalance activities of LAA and NAAAR were found in E. coli cell coexpressing laa and naaar genes, which resulted in the accumulation of an intermediate, NAc‐l‐HPA, in the early stage of conversion and a low productivity of 0.83 mmol l‐HPA/L h. The results indicated that low activity of LAA present in the biomass is the rate‐limiting factor in l‐HPA production. In the case of two whole cells with separately expressed enzyme, the enzymatic activities of LAA and NAAAR could be balanced by changing the loading of individual cells. When the activities of two enzymes were fixed at 3600 U/L, 99.9% yield of l‐HPA could be reached in 1 h, with a productivity of 10 mmol l‐HPA/L h. The cells can be reused at least six cycles at a conversion yield of more than 96%. This is the first NAAAR/LAA process using NAc‐HPA as substrate and recombinant whole cells containing Deinococcus enzymes as catalysts for the production of l‐HPA to be reported.
Plasmid DNA Delivery by d‐Alanine‐Deficient Listeria monocytogenes
Authors: Simon Benjamin E. , Ybarra Noel , Bonneval Aimée O. , Barry Ronald A.
Published: September 2006

Optimal DNA vaccine efficacy requires circumventing several obstacles, including low immunogenicity, a need for adjuvant, and the costs of purifying injection grade plasmid DNA. Bacterial delivery of plasmid DNA may provide an efficient and low‐cost alternative to plasmid purification and injection. Also, the bacterial vector may exhibit potential as an immune adjuvant in vivo. Thus, we elected to examine the use of cell‐wall‐deficient Listeria monocytogenes as a DNA delivery vehicle in vitro. First, the d‐alanine‐deficient (Δdal‐dat) L. monocytogenes strain DP‐L3506, which undergoes autolysis inside eukaryotic host cells in the absence of d‐alanine, was transformed with a plasmid encoding green fluorescent protein (GFP) under control of the CMV promoter (pAM‐EGFP). Then COS‐7 and MC57G cell lines were infected with the transformed DP‐L3506 at various multiplicities of infection (MOI) in the presence or absence of d‐alanine. Subsequent GFP expression was observed in both cell lines by 24 h post‐infection with DP‐L3506(pAM‐EGFP). Notably, no GFP positive cells were observed when d‐alanine was omitted. Although transfection efficiency initially increased as a result of d‐alanine supplementation, high concentration or long‐term supplementation led to sustained bacterial growth that killed the infected host cells, resulting in fewer GFP‐expressing cells. Thus, efficient DNA delivery by transformed bacteria must balance bacterial invasion and survival with target cell health and survival.
Radial diffusion of geomagnetically trapped protons observed by the Galileo Energetic Particle Detector
Authors: Alinejad Naser , Armstrong Thomas P.
Published: September 2006

The Galileo spacecraft encountered the Earth once on 8 December 1990 (Earth‐I) and again on 8 December 1992 (Earth‐II). These flybys provided excellent opportunities to evaluate the performance of the Energetic Particle Detector (EPD) and establish analysis procedures in a relatively well‐known environment. Further, because Galileo's Earth flyby trajectories were very rapid and nearly radial, the radiation belt measurements provided an excellent “snapshot” of trapped radiation. Because of the rapid flyby and the 20‐s spin period of Galileo, great care had to be taken to remove time aliasing from the pitch angle distributions. Large anisotropies were also present due to intrinsic density gradients. Spherical harmonics were fitted to the pitch and phase distributions in order to obtain fluxes from which phase space densities could be computed. The phase space density (PSD) was calculated from the fitted count rate for the particles (protons) that conserve the first and second adiabatic invariants. The values of 10.0, 15.0, 20.0, 25.0 30.0, 35.0, 40.0, 45.0, and 50.0 MeV/G were used for the first adiabatic invariant, and the values of 0.10, 0.15, 0.20, 0.25, 0.30, and 0.50 G0.5 RE were used for the second adiabatic invariant to determine the PSD from Earth‐I and Earth‐II observations. The extracted PSDs were examined for radial diffusion. Results show there is no unique global dependency of the diffusion coefficient to L, except for a limited region of the first and second adiabatic invariants.