AI language models in human reproduction research: exploring ChatGPT's potential to assist academic writing.

Artificial intelligence (AI)-driven language models have the potential to serve as an educational tool, facilitate clinical decision-making, and support research and academic writing. The benefits of their use are yet to be evaluated and concerns have been raised regarding the accuracy, transparency, and ethical implications of using this AI technology in academic publishing. At the moment, Chat Generative Pre-trained Transformer (ChatGPT) is one of the most powerful and widely debated AI language models. Here, we discuss its feasibility to answer scientific questions, identify relevant literature, and assist writing in the field of human reproduction. With consideration of the scarcity of data on this topic, we assessed the feasibility of ChatGPT in academic writing, using data from six meta-analyses published in a leading journal of human reproduction. The text generated by ChatGPT was evaluated and compared to the original text by blinded reviewers. While ChatGPT can produce high-quality text and summarize information efficiently, its current ability to interpret data and answer scientific questions is limited, and it cannot be relied upon for a literature search or accurate source citation due to the potential spread of incomplete or false information. We advocate for open discussions within the reproductive medicine research community to explore the advantages and disadvantages of implementing this AI technology. Researchers and reviewers should be informed about AI language models, and we encourage authors to transparently disclose their use.

Experimental noise cutoff boosts inferability of transcriptional networks in large-scale gene-deletion studies.

Generating a comprehensive map of molecular interactions in living cells is difficult and great efforts are undertaken to infer molecular interactions from large-scale perturbation experiments. Here, we develop the analytical and numerical tools to quantify the fundamental limits for inferring transcriptional networks from gene knockout screens and introduce a network inference method that is unbiased with respect to measurement noise and scalable to large network sizes. We show that network asymmetry, knockout coverage and measurement noise are central determinants that limit prediction accuracy, whereas the knowledge about gene-specific variability among biological replicates can be used to eliminate noise-sensitive nodes and thereby boost the performance of network inference algorithms.

Strategies for improving outcome of assisted reproduction in women with polycystic ovary syndrome: systematic review and meta-analysis.

OBJECTIVES: To identify, appraise and summarize the current evidence regarding the efficacy of strategies aimed at improving assisted reproductive techniques in women with polycystic ovary syndrome (PCOS). METHODS: A comprehensive literature search of the standard medical databases was performed. The last electronic search was run in July 2015. The primary outcome measures were live birth/ongoing pregnancy and ovarian hyperstimulation syndrome (OHSS). The secondary outcome measures were clinical pregnancy and miscarriage. RESULTS: We screened 1021 records and completely assessed 173, finally including 66 studies in the quantitative analysis. Many different interventions were assessed, however the overall quality of the studies was low. We observed moderate-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (relative risk (RR), 0.95 (95% CI, 0.84-1.08)), or clinical pregnancy (RR, 1.02 (95% CI, 0.91-1.15)) when comparing antagonist and agonist protocols for ovarian stimulation. Additionally, we found low-quality evidence that metformin improves live birth/ongoing pregnancy (RR, 1.28 (95% CI, 1.01-1.63)) and clinical pregnancy rates (RR, 1.26 (95% CI, 1.04-1.53)) when compared with placebo or no intervention. We further found low-quality evidence that there is no clinically relevant difference in live birth/ongoing pregnancy rates (RR, 1.03 (95% CI, 0.80-1.34)) and clinical pregnancy rates (RR, 0.99 (95% CI, 0.81-1.22)) when comparing human menopausal gonadotropin for inducing ovulation and artificial preparation with estradiol valerate for endometrial preparation for frozen embryo transfer (FET). Low-quality evidence suggests that mannitol compared with no intervention (RR, 0.54 (95% CI, 0.39-0.77)) and antagonist protocols compared with agonist protocols (RR, 0.63 (95% CI, 0.49-0.80)) reduce rates of OHSS. CONCLUSION: There is low- to moderate-quality evidence suggesting that antagonist protocols are preferable to agonist ones, because they reduce the incidence of OHSS without interfering with clinical pregnancy and live birth for women with PCOS. Additionally there is low-quality evidence pointing to a benefit of metformin supplementation on clinical pregnancy and live birth; and that ovulation induction and administration of estradiol seem to be equally effective for endometrial preparation before FET for women with PCOS. For all other interventions, the evidence is of very low quality, not allowing any meaningful conclusions to be drawn. Estrategias para mejorar el resultado de la reproducción asistida en mujeres con síndrome de ovario poliquístico: revisión sistemática y metaanálisis RESUMEN OBJETIVOS: Identificar, evaluar y resumir la evidencia actual sobre la eficacia de las estrategias para mejorar las técnicas de reproducción asistida en mujeres con síndrome de ovario poliquístico (SOP). MÉTODOS: Se realizó una búsqueda exhaustiva de literatura en las bases de datos médicas estándar. La última búsqueda electrónica se realizó en julio de 2015. Las medidas de resultado primarias fueron los nacimientos vivos/embarazos en curso y el síndrome de hiperestimulación ovárica (SHO). Las medidas de resultado secundarias fueron el embarazo confirmado ecográficamente y el aborto. RESULTADOS: Se cribaron 1021 registros, de los que se evaluaron por completo 173, para finalmente incluir 66 estudios en el análisis cuantitativo. Aunque se evaluaron muchas intervenciones diferentes, en general la calidad de los estudios fue baja. Se observó evidencia de calidad moderada de que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (riesgo relativo (RR): 0,95 (IC 95%, 0,84-1,08)), o de embarazos confirmados ecográficamente (RR: 1,02 (IC 95%, 0,91-1,15)), cuando se comparan los protocolos de antagonistas y agonistas para la estimulación ovárica. Además, se encontró evidencia de baja calidad en que la metformina mejora las tasas de nacimientos vivos/embarazos en curso (RR: 1,28 (IC 95%, 1,01-1,63)) y de embarazos confirmados ecográficamente (RR: 1,26 (IC 95%, 1,04-1,53)) en comparación con un placebo o la no intervención. Se encontró también evidencia de baja calidad en que no hay diferencias relevantes clínicamente en las tasas de nacimientos vivos/embarazos en curso (RR: 1,03 (IC 95%, 0,80-1,34)) y las tasas de embarazos confirmados ecográficamente (RR: 0,99 (IC 95%, 0.81-1,22)) al comparar la gonadotropina menopáusica humana para la inducción de la ovulación y la preparación artificial con el valerato de estradiol para preparar el endometrio para la transferencia de embriones congelados (TEC). La baja calidad de la evidencia sugiere que el manitol, en comparación con la no intervención (RR: 0,54 (IC 95%, 0,39-0,77)), y los protocolos de antagonistas, en comparación con los protocolos de agonistas (RR: 0,63 (IC 95%, 0,49-0,80)), reducen las tasas de SHO. CONCLUSIÓN: Hay evidencia de calidad baja a moderada que sugiere que los protocolos de antagonistas son preferibles a los de agonistas, ya que reducen la tasa de SHO sin interferir con el embarazo confirmado ecográficamente y los nacimientos vivos en las mujeres con SOP. Además, existe evidencia de baja calidad que indica un beneficio del uso de metformina como aporte suplementario en embarazos confirmados ecográficamente y en nacimientos vivos; y que la inducción de la ovulación y la administración de estradiol parecen ser igualmente eficaces para la preparación del endometrio antes de la TEC en mujeres con SOP. Para el resto de procedimientos, la evidencia es de muy baja calidad, y por ello no permite extraer conclusiones importantes.

Maternal and neonatal outcomes in pregnant women with PCOS: comparison of different diagnostic definitions.

STUDY QUESTION: Does the prevalence of adverse maternal and neonatal outcomes vary in women diagnosed with polycystic ovary syndrome (PCOS) according to different definitions? SUMMARY ANSWER: A comparison of different criteria revealed that there is a substantial risk for perinatal complications in PCOS women, regardless of the used definition. WHAT IS KNOWN ALREADY: Pregnant women with PCOS are susceptible to perinatal complications. At present, there are three main definitions for PCOS. So far, we are aware of only one study, which found that the elevated risk for complications varied widely depending on the different phenotypes and features but only considered a relatively small sample size for some of the phenotypes. STUDY DESIGN, SIZE, DURATION: Retrospective matched cohort study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Data of primiparous women with PCOS according to ESHRE/ASRM 2003 criteria and healthy controls giving birth to neonates ≥500 g were included. A total of 885 women were analysed: out of 177 women with PCOS, 85 (48.0%) met the National Institutes of Health (NIH) 1990 criteria, another 14 (7.9%) featured the additional phenotypes defined by The Androgen Excess and PCOS Society (AE-PCOS) 2006 criteria, 78 (44.1%) were classified as PCOS exclusively by the ESHRE/ASRM 2003 definition, and 708 represented the control group. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of adverse maternal (49.4 versus 64.3 versus 60.3%, P = 0.313) and neonatal (27.1 versus 35.7 versus 23.1%, P = 0.615) outcomes did not differ within the three PCOS groups (ESHRE/ASRM, NIH, AE-PCOS, respectively). Compared with healthy controls, the risk for maternal complications was increased in PCOS patients [odds ratio (OR) 2.57; 95% confidence interval (CI) 1.82-3.64; P < 0.001] while there was no difference in neonatal complications (OR 0.83; 95% CI 0.56-1.21; P = 0.343). LIMITATIONS, REASONS FOR CAUTION: A limitation of our study is its retrospective design and the relatively small sample size, particularly in the AE-PCOS subgroup. WIDER IMPLICATIONS OF THE FINDINGS: Since women with PCOS have, regardless of the used definition, a high risk of maternal and neonatal complications they should be informed and advised to follow regular checks in units where problems can be detected early to allow specialized care. STUDY FUNDING/COMPETING INTERESTS: Marietta Blau Grant (Austrian Agency for International Cooperation in Education and Research; OeAD-GmbH) and mobility scholarship (Medical University of Graz).

Surveillance for respiratory health care-associated infections among inpatients in 3 Kenyan hospitals, 2010-2012.

BACKGROUND: Although health care-associated infections are an important cause of morbidity and mortality worldwide, the epidemiology and etiology of respiratory health care-associated infections (rHAIs) have not been documented in Kenya. In 2010, the Ministry of Health, Kenya Medical Research Institute, and Centers for Disease Control and Prevention initiated surveillance for rHAIs at 3 hospitals. METHODS: At each hospital, we surveyed intensive care units (ICUs), pediatric wards, and medical wards to identify patients with rHAIs, defined as any hospital-onset (≥3 days after admission) fever (≥38°C) or hypothermia (<35°C) with concurrent signs or symptoms of acute respiratory infection. Nasopharyngeal and oropharyngeal specimens were collected from these patients and tested by real-time reverse transcription polymerase chain reaction for influenza and 7 other viruses. RESULTS: From April 2010-September 2012, of the 379 rHAI cases, 60.7% were men and 57.3% were children <18 years old. The overall incidence of rHAIs was 9.2 per 10,000 patient days, with the highest incidence in the ICUs. Of all specimens analyzed, 45.7% had at least 1 respiratory virus detected; 92.2% of all positive viral specimens were identified in patients <18 years old. CONCLUSION: We identified rHAIs in all ward types under surveillance in Kenyan hospitals. Viruses may have a substantial role in these infections, particularly among pediatric populations. Further research is needed to refine case definitions and understand rHAIs in ICUs.

Etiology and perinatal outcome of polyhydramnios.

PURPOSE: To determine causes of polyhydramnios and the respective perinatal outcome. MATERIALS AND METHODS: We retrospectively analyzed cases with polyhydramnios at the Medical University Graz, Austria from 2003 - 2011. Inclusion criteria were single deepest pocket ≥ 8  cm, amniotic fluid index ≥ 25  cm, each of the latter parameters > 95th percentile or subjective impression. Etiologies, including TORCH infection, diabetes and congenital malformations, as well as perinatal outcome were evaluated. RESULTS: Out of 860 singleton pregnancies with polyhydramnios, 2.9 % had positive TORCH serology, 8.5 % had congenital anomalies, 19.8 % had maternal diabetes, and 68.8 % were idiopathic. The most common fetal anomalies were cardiac defects (32.9 %). Elective caesarean sections were more common in the groups with malformations and maternal diabetes. Low birth weight combined with severe polyhydramnios or maternal diabetes was associated with malformations. CONCLUSION: Diagnosis of polyhydramnios should prompt glucose-tolerance testing, detailed sonography including fetal echocardiography, and TORCH serology. Especially pregnancies with polyhydramnios and small fetuses as well as those with maternal diabetes should be carefully evaluated for malformations.

Procedure-related complications after genetic amniocentesis and chorionic villus sampling.

PURPOSE: Amniocentesis (AC) and chorionic villus sampling (CVS) play an important role in the diagnosis of genetic anomalies. The aim of this study was to evaluate presentable numbers of procedure-related complications of genetic interventions in a tertiary referral hospital. MATERIALS AND METHODS: The pregnancy outcome of women who underwent genetic AC or CVS during 2003-2010 at the Department of Obstetrics and Gynecology, Medical University of Graz, Austria, was analyzed retrospectively. The primary outcome was miscarriage or membrane rupture after an invasive procedure. Only singleton gestations were included. RESULTS: 1,569 AC procedures and 334 CVS procedures (234 transabdominal, 99 transcervical, 1 with undocumented route) were performed. Of these, 57 cases were excluded from further analysis because of severe anomalies. Complete outcome data were available for 93.17% of cases. In 164 (8.89%) cases the pregnancy was terminated due to genetic anomalies or severe malformations. In the remaining collective 10 of 1,342 (0.75%) AC procedures, 3 of 150 (2.00%) transabdominal CVS procedures and 2 of 64 (3.13%) transcervical CVS procedures lead to complications resulting in miscarriage < 24 weeks (n = 13) or rupture of membranes (n = 2) within 2 weeks after procedure. Complication rates were significantly higher after CVS than after AC (OR 3.19). CONCLUSION: Over an observation period of seven years, the complication rates after AC, transabdominal CVS and transcervical CVS were 0.75%, 2.00% and 3.13%, respectively. These results are comparable to recent international investigations.

Laparoscopic techniques for investigating the equine oviduct.

REASONS FOR PERFORMING STUDY: The diagnostic and therapeutic options for oviduct disorders in the mare are limited. The current best techniques require exploratory surgery under general anaesthesia or flank laparotomy. HYPOTHESIS: The orthograde flushing of the oviduct for diagnostic or therapeutic options is possible using laparoscopic techniques in the standing sedated mare. METHODS: Development of a laparoscopic technique for catheterisation of the infundibulum and flushing of the oviduct (sterile methylene blue solution) in the standing sedated mare was examined in 2 experiments. The first involved a transvaginal laparoscopic approach, the second a laparoscopic flank approach. Passage of fluid into the uterus was assessed by post operative hysteroscopy. RESULTS: In Experiment I, visualisation of the infundibulum was possible (left side 7/8 cases, right side in 6/8 cases). The beginning of the oviductal ampulla could be seen in 3 of 8 cases on the left side. An adequate opening of the infundibulum and visualisation or catheterisation of the abdominal ostium were not possible. In Experiment II, catheterisation of the ampulla was successful in 7 of 11 cases, and in 5 of these 7 cases the injected fluid could be identified in the uterus by post operative hysteroscopy. CONCLUSION: A transvaginal laparoscopic approach to the oviduct is not appropriate for oviductal flushing in the mare. However, a laparoscopic flank-approach permits investigation and flushing of the oviduct. POTENTIAL RELEVANCE: Laparoscopic flushing could become a practical method for diagnosis and therapy of oviduct disorders and a minimally invasive technique for collection of young embryos or the transfer of gametes (GIFT).

Minimal cross-infection risk through Icare rebound tonometer probes: a useful tool for IOP-screenings in developing countries.

AIMS: Recently, a new rebound tonometer has been introduced into the market, which might be useful for glaucoma screenings in developing countries. Disposable probes, that are potentially reusable, are recommended by the manufacturer. Our study aimed to address the question of microbial transmission risks if the probes are reused. METHODS: IOP measurements were obtained from 100 healthy eyes. The used probes were inoculated on broth and culture media. In addition, 10 probes were analyzed using environmental scanning electron microscopy in saturated hydrogen-steam atmosphere after usage and wipe disinfection technique with Sekusept 4% solution or Isopropanol 70%. RESULTS: No bacterial or fungal growth could be detected in any of the inoculated agar plates or broth tubes. No microorganisms, clumps of cells, or single intact epithelium cells were detected in any of the probes using environmental scanning electron microscopy. Cell debris was detected on seven probes; three probes were completely free of any residual cell elements. CONCLUSION: Transmission of possibly infective material through reused probes is significantly less than for reusable Goldmann probes if the same sterilization protocols are applied. Re-usage of the probes appears safe and is helpful in avoiding unnecessary costs.

[Biometry in cataract camps. Experiences from north Kenya]. / Biometrie in Katarakt-Camps. Erfahrungen aus Nordkenia.

BACKGROUND: Biometry has the potential to improve refractive outcomes of cataract surgery in developing countries. However, the procedure is difficult to carry out in remote areas. PATIENTS AND METHODS: The feasibility of automated biometry using portable devices was assessed in an eye camp in a remote Kenyan community and reasons for failure were documented. PC-IOLs in the range of 17-27 dioptres (dpt) were implanted and a model was created to predict spherical refractive error if a standard 22 dpt lens had been used. RESULTS: In 104 out of 131 eyes (80%) biometry was possible. Failure to obtain K-readings in eyes with coexisting corneal pathology was the main limiting factor. The calculated mean IOL strength to achieve emmetropia was 21.56 dpt with a SD=1.96 (min: 14.78 dpt, max: 27.24 dpt). If 22 dpt lenses had been implanted around 20% would have had an error of more than 2 dpt and 7% an error of more than 3 dpt. CONCLUSION: Biometry is a challenging procedure in remote areas where comorbidities are common. However, without biometry and implantation of different IOL powers poor refractive outcome can be expected in around 20% of patients.

[Training program for vitreoretinal surgery in Nairobi, Kenya from 2000 - 2006]. / Trainingsprogramm zur vitreoretinalen Chirurgie in Nairobi, Kenia, in den Jahren 2000 - 2006.

BACKGROUND: After the U. S. Embassy bombing in 1998 in Nairobi, Kenya, a relief operation was immediately initiated by the Department of Ophthalmology of the Ludwig Maximilians University (LMU) Munich, Germany. Surgical devices and material (such as a vitrectomy unit, silicon oil, perfluorodecalin, intraocular lenses, sutures) were supplied to operate on 42 ocular-injured victims of this bombing attack. Apart from these specific operations in Kenya, there is a big need for vitreoretinal surgery in East Africa, as in all other developing countries. Therefore, a vitreoretinal training program was started in 2000 in Nairobi, Kenya. We report about the first 7 years of collaboration between the Ludwig Maximilians University of Munich, Germany and the University of Nairobi in cooperation with the Kenyatta National Hospital, Kenya. MATERIAL AND METHODS: The training program was based on an annual project week in which the author (CLS) carried out vitreoretinal surgery himself and assisted and supervised surgery done by the local Kenyan colleagues at the Kenyatta National Hospital. Within the observation period of the present work (2000 - 2006) the following data were collected: number and kind of surgery, indications, surgeons, grading of eye pathology and the surgical procedure, time to prepare for surgery and duration of surgery. RESULTS: In total, 293 vitreoretinal surgeries were performed during the observation period. Surgeries carried out by the local Kenyan colleagues independently, without intervention of the author, increased from 29.4 % (2000) to 78.6 % (2006). Due to a constant development in the learning process during the project week more severe cases were treated and preparation time for surgery from the nursing side has shortened. CONCLUSIONS: By initiating a project week with high frequency surgery, supported by a highly experienced visiting surgeon, vitreoretinal surgery can be successfully set up in an ophthalmic clinic of a developing country. This approach has some advantages when compared to long-period projects, especially for the purposes of sustainability. However, to be successful it requires systematic planning which is described in this article.

Effects of tryptophan supplementation on plasma tryptophan and related hormone levels in heifers and dairy cows.

This study was conducted to investigate the effects of rumen-protected tryptophan (125 g tryptophan per day) in heifers and dairy cows. Blood samples from dairy cows and heifers were collected for 24h in 3-h intervals on the day before tryptophan supplementation, on day 2, 5 and 7 of tryptophan supplementation, and in heifers additionally on d 14 after tryptophan supplementation was ceased. Plasma tryptophan, melatonin, serotonin, and prolactin concentrations were determined. Tryptophan plasma concentrations on d 5 were augmented at day (11:00 h) and nighttime (02:00 h), (P<0.05) in response to tryptophan supplementation in heifers by 119% and in dairy cows by 47%, respectively, as compared with d 0. Melatonin increased (P<0.05) in response to tryptophan supplementation in heifers, but not in cows. The effect of tryptophan supplementation on plasma tryptophan and melatonin was reversible as demonstrated in heifers on d 14 after cessation of tryptophan supplementation. Serotonin and prolactin in plasma did not respond to tryptophan supplementation. However, milk yield during morning milking increased significantly in tryptophan supplemented cows on d 1, 3 and 4 as compared to the day before tryptophan supplementation. Additional blood samples were taken during afternoon milking in cows at 1-min intervals for the analyses of oxytocin and prolactin on the day before the start and on d 7 of tryptophan supplementation. Milk flow curves were recorded during milking. No effect of tryptophan supplementation on the milking related release of oxytocin and prolactin and on any characteristic of milk flow was observed. In conclusion, tryptophan supplementation caused increased plasma tryptophan in cows and heifers and plasma melatonin in heifers. However, plasma serotonin, prolactin and oxytocin release in cows remained unchanged by tryptophan supplementation. Milk yield at morning milking increased slightly and transiently in response to tryptophan supplementation.

Exponential decay of GC content detected by strand-symmetric substitution rates influences the evolution of isochore structure.

The distribution of guanine and cytosine nucleotides throughout a genome, or the GC content, is associated with numerous features in mammals; understanding the pattern and evolutionary history of GC content is crucial to our efforts to annotate the genome. The local GC content is decaying toward an equilibrium point, but the causes and rates of this decay, as well as the value of the equilibrium point, remain topics of debate. By comparing the results of 2 methods for estimating local substitution rates, we identify 620 Mb of the human genome in which the rates of the various types of nucleotide substitutions are the same on both strands. These strand-symmetric regions show an exponential decay of local GC content at a pace determined by local substitution rates. DNA segments subjected to higher rates experience disproportionately accelerated decay and are AT rich, whereas segments subjected to lower rates decay more slowly and are GC rich. Although we are unable to draw any conclusions about causal factors, the results support the hypothesis proposed by Khelifi A, Meunier J, Duret L, and Mouchiroud D (2006. GC content evolution of the human and mouse genomes: insights from the study of processed pseudogenes in regions of different recombination rates. J Mol Evol. 62:745-752.) that the isochore structure has been reshaped over time. If rate variation were a determining factor, then the current isochore structure of mammalian genomes could result from the local differences in substitution rates. We predict that under current conditions strand-symmetric portions of the human genome will stabilize at an average GC content of 30% (considerably less than the current 42%), thus confirming that the human genome has not yet reached equilibrium.

Incontinentia lactis: physiology and anatomy conducive to milk leakage in dairy cows.

Incontinentia lactis is a possible predisposing factor for an elevated level of intramammary infection. The goal of the present study was to investigate possible causes of incontinentia lactis in dairy cows. Two farms that differed in breed composition, but that had similar average milk yields were studied: herd A, 28 kg/d, 31 Red Holstein cows; and herd B, 26 kg/d, 16 Brown Swiss cows. Herd A was classified into 2 groups: incontinentia lactis (ILA group) and control, whereas herd B was exclusively a control herd. Milk samples that represented foremilk and the main milk fraction were collected during 4 milking sessions. In addition, milk leakage samples from the ILA group were collected at different time intervals from 0 to 5 h before milking. Measurements of the teat, milk flow, fractions of cisternal and alveolar milk, intramammary pressure, and blood oxytocin pattern also were obtained. The ILA cows did not have differences in fat content between milk leakage and cisternal milk fraction. Milk fat content, however, increased during milking in response to continuous milk ejection (1.95, 1.99, and 4.61% for milk leakage, cisternal, and main milk samples, respectively). Teat canals were 9% shorter in the ILA cows, which showed greater milk yield, peak, and average flow rates. Quarter cisternal milk yield of ILA cows tended to be greater (0.50 vs. 0.23 and 0.28 kg for ILA and controls from herds A and B, respectively), whereas percentages of cistern milk and alveolar milk did not differ from controls. The greater pressure in the ILA group, both before and after manual udder stimulation (ILA: 4.0 and 6.4 kPa; control: 2.0 and 5.0 kPa, respectively), could be an important cause for the leakage. Nevertheless, the increase in IMP that occurred after udder preparation affirms that milk ejection occurred in response to the tactile teat stimulation, but not before the onset of leakage. Blood oxytocin concentration in ILA cows was low until the start of udder preparation and increased in response to the milking stimulus (reaffirming the hypothesis that milk leakage occurred in the absence of milk ejection). In conclusion, milk losses by leakage are likely due to the large amount of cisternal milk, which creates pressure and causes leakage, in the absence of milk ejection.

Conjunctival squamous cell carcinoma in patients with human immunodeficiency virus infection seen at two hospitals in Kenya.

OBJECTIVE: To estimate the prevalence and pattern of conjuctival squamous cell carcinoma (CSCC) in patients with HIV infection. DESIGN: A hospital based cross sectional study. SETTING: Kenyatta National Hospital (KNH) and Kikuyu Eye Unit (KEU) during the period November 2003 and May 2004. SUBJECTS: Four hundred and nine HIV positive patients. RESULTS: Four hundred and nine HIV positive patients aged 25 to 53 years were screened. Male to Female ratio was 1:1. One hundred and three had conjunctival growths. Thirty two had histologically proven conjunctiva squamous cell carcinoma (CSCC). Estimated prevalence of CSCC among HIV positive patients was 7.8%. The average duration of growth of the conjunctival masses was 21.8 months. The average size of the lesions at the time of presentation was 6.6 mm. Twenty two (68.8%) patients had primary CSCC, while ten (31.2%) had recurrent lesions. The pattern of the histopathology results was: fifteen (46.9%) patients had poorly differentiated squamous cell carcinoma; nine (28%) had moderately differentiated squamous cell carcinoma; five patients (15.6%) had CIN; two patients (6.3%) had dysplasia and one patient (3.1%) had a well differentiated squamous cell carcinoma. CONCLUSIONS: Prevalence of CSCC in HIV/AIDS patients was 7.8%. Patients present late with advanced lesions. Recurrence rates from previous surgery are high. The often uncharacteristic complaints and findings on presentation complicate the clinical diagnosis. Active search for early manifestations of CSCC in HIV / AIDS patients, complete surgical excision and close follow up is necessary. Alternative treatment methods and techniques like the topical use of antimetabolites should be explored further.

Quantitative data generation for systems biology: the impact of randomisation, calibrators and normalisers.

Systems biology is an approach to the analysis and prediction of the dynamic behaviour of biological networks through mathematical modelling based on experimental data. The current lack of reliable quantitative data, especially in the field of signal transduction, means that new methodologies in data acquisition and processing are needed. Here, we present methods to advance the established techniques of immunoprecipitation and immunoblotting to more accurate and quantitative procedures. We propose randomisation of sample loading to disrupt lane correlations and the use of normalisers and calibrators for data correction. To predict the impact of each method on improving the data quality we used simulations. These studies showed that randomisation reduces the standard deviation of a smoothed signal by 55% +/- 10%, independently from most experimental settings. Normalisation with appropriate endogenous or external proteins further reduces the deviation from the true values. As the improvement strongly depends on the quality of the normaliser measurement, a criteria-based normalisation procedure was developed. Our approach was experimentally verified by application of the proposed methods to time course data obtained by the immunoblotting technique. This analysis showed that the procedure is robust and can significantly improve the quality of experimental data.