Influence of the dealcoholisation by osmotic distillation on the sensory properties of different beer types.

A comparative study was performed to better understand the feasibility of osmotic distillation as a process to produce a low-alcohol beer. Four diverse commercial beers styles were considered. The regular and corresponding dealcoholised beers were compared. The quality attributes and the volatile compounds loss after the dealcoholisation were checked. The work focused on the sensory properties of the obtained samples. A trained panel evaluated how the chosen sensory descriptors were influenced by the treatment. The results of quality attributes and volatile compounds were in line with works previously published by the authors. Interestingly, the results highlighted that beer characterized by malty character is more suitable than pale lager to be dealcoholised by the osmotic distillation process. The low alcohol milk stout and stout flavour profile, especially in terms of taste, was like the corresponding regular beer. Osmotic distillation was demonstrated to be a feasible process to produce low-alcohol beer.

2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety.

Studies have linked the serine-threonine kinase MAP4K4 to the regulation of a number of biological processes and/or diseases, including diabetes, cancer, inflammation, and angiogenesis. With a majority of the members of our lead series (e.g., 1) suffering from time-dependent inhibition (TDI) of CYP3A4, we sought design avenues that would eliminate this risk. One such approach arose from the observation that carboxylic acid-based intermediates employed in our discovery efforts retained high MAP4K4 inhibitory potency and were devoid of the TDI risk. The medicinal chemistry effort that led to the discovery of this central nervous system-impaired inhibitor together with its preclinical safety profile is described.

Effects of Operating Conditions during Low-Alcohol Beer Production by Osmotic Distillation.

Osmotic distillation (OD) is a membrane technology most commonly used for liquid concentration, but recently there has been an increased interest in ethanol removal from alcoholic beverages. The aim of this paper is to investigate the effect of the variation of some operating conditions (temperature, flow rate, type and amount of stripping solution), specifically in regard to the effect on quality and sensory properties of the dealcoholized beers. The results indicated that temperature and flow rate variation showed no significant effect, whereas stripping solution variation had substantial effects mainly in terms of the ethanol removed. A cost appraisal showed that the operating costs were high mainly because of the cost of the stripping water. However, it is important to consider the final stripping solution, which is slightly alcoholic and enriched in flavor. For this reason, it could be reused in the manufacture of beverages, for instance as high gravity beer dilution water.

Retrospective evaluation of current-based impedance compensation defibrillation in out-of-hospital cardiac arrest.

OBJECTIVE: Transthoracic impedance (TTI) is a principal parameter that influences the intracardiac current flow and defibrillation outcome. In this study, we retrospectively evaluated the performance of current-based impedance compensation defibrillation in out-of-hospital cardiac arrest (OHCA) patients. METHODS: ECG recordings, along with TTI measurements were collected from multiple emergency medical services (EMSs) in the USA. All the EMSs in this study used automated external defibrillators (AEDs) which employing rectilinear biphasic (RLB) waveform. The distribution and change of TTI between successive shocks, the influence of preceding shock results on the subsequent shock outcome, and the performance of current-based impedance compensation defibrillation was evaluated. RESULTS: A total of 1166 shocks from 594 OHCA victims were examined in this study. The average TTI for the 1st shock was 134.8 Ω and a significant decrease in TTI was observed for the 2nd (p<0.001) and 3rd (p=0.033) sequential escalating shock. But TTI did not change after the 3rd shock. A higher success rate was observed for shocks with preceding defibrillation success. The success rate remained unchanged over the whole spectrum of TTI. CONCLUSION: The average TTI was relatively higher in this OHCA population treated with RLB defibrillation as compared with previously reported data. TTI was significantly decreased after 1st and 2nd successive escalating shock but kept constant after the 3rd shock. Preceding shock success was a better predictor of subsequent defibrillation outcome other than TTI. Current-based impedance compensation defibrillation resulted in equivalent success rate for high impedance patients when compared with those of low impedance.

Current is better than energy as predictor of success for biphasic defibrillatory shocks in a porcine model of ventricular fibrillation.

OBJECTIVE: The evidence that monophasic defibrillation success is mainly determined by current is secure. However, modern defibrillators use biphasic waveforms. The aim of this study was to compare energy, peak voltage and peak current in predicting biphasic shock success in a porcine model of ventricular fibrillation (VF) where the impedance varies within a wide of ranges. METHODS: In 14 domestic male pigs weighing between 27 and 38 kg, VF was electrically induced and untreated for 15 s. Animals were randomized to receive defibrillation attempts from one of two defibrillators with different impedance compensation methods. A grouped up-and-down defibrillation threshold testing protocol was used to maintain the average success rate in the neighborhood of 50%. After a recovery interval of 5 min, the testing sequence was repeated for a total of 60 test shocks for each animal. RESULTS: A high defibrillation success was observed when high peak current was delivered. The area under ROC curve for predicting shock success was 0.681 for peak current, 0.585 for peak voltage and 0.562 for energy. The odds ratio revealed that peak current was a better predictor (OR=1.321, p<0.001) for defibrillation outcome compared with energy (OR=0.979, p<0.001) and peak voltage (OR=1.000, p=0.69) when multivariable logistic regression was conducted. CONCLUSION: In this porcine model of VF within a wide range of transthoracic impedance, peak current was a better indicator for shock success than the currently used energy for biphasic defibrillatory shocks. This finding may encourage design of new current-based biphasic defibrillators.

Are the anticipatory pathways in lecithotrophic larvae that delay metamorphosis adaptations? (A review).

During anticipatory development in lecithotrophic larvae that delay metamorphosis, the growth and differentiation of features of the adult action system continue to develop at a slow pace even though they do not become functional. After metamorphosis occurs, the larger size and advanced development of these components may allow juveniles to initially grow at a faster rate than they normally would. Anticipatory development has been demonstrated in archeogastropods, some solitary ascidians and a hydrozoan. In the gastropod Haliotis and the hydrozoan Phialidium anticipatory development increases the initial growth rate of juveniles. In Haliotis and ascidians all of the larvae of a given female that live long enough exhibit anticipatory development. In Phialidium, the ability of a given female to produce larvae that can exhibit anticipatory development is a maternal polymorphic character. In Haliotis and solitary ascidians that exhibit anticipatory development, it appears to be a slower version of the rapid developmental changes that occur in parts of the adult action system at metamorphosis. In Phialidium, developmental changes in relative sizes of the different presumptive regions of the polyp are slowly altered prior to and independently of metamorphosis. Anticipatory development is not linked to the decrease in the size or nutrient reserves of older larvae but to the length of their larval period. From an evolutionary perspective, the mechanisms that operate during anticipatory development are probably of adaptive significance for lecithotrophic larvae of species that spend variable amounts of time in the water column because of a patchy distribution of appropriate settlement cues. The developmental mechanisms that underlie anticipatory development may have been used during the transition from lecithotrophy to planktotrophy.

Chronic administration of an aglycosylated murine antibody of ponezumab does not worsen microhemorrhages in aged Tg2576 mice.

Cerebral vasogenic edema and microhemorrhages are potential safety concerns for compounds intended to treat subjects with Alzheimer's disease (AD) by targeting amyloid ß (Aß). Ponezumab (PF-04360365) is an investigational anti-Aß monoclonal antibody. Two hundred female mice (APP(K670N;M671L); Tg2576) 16-19 months old received an aglycosylated CHO-derived murine surrogate of ponezumab by intraperitoneal administration once weekly for up to 26 weeks at doses of 0, 10, 30, or 100 mg/kg. Drug exposure and plasma Aß levels increased with increasing dose. After 26 weeks, the 100 mg/kg group had significantly greater plasma levels of Aß(1-x) and Aß(x-40) than the vehicle group (p < 0.001). Brain microhemorrhages were identified histologically using hematoxylin and eosin and/or Perls' Prussian blue iron staining. The incidence in the vehicle group was equal to or higher than those of the treated groups. There was no evidence of vasogenic edema. In summary, intraperitoneal administration of a murine surrogate of ponezumab to aged Tg2576 mice for up to 6 months did not produce any compound-related brain microhemorrhage or other pathologies.

Coronary perfusion pressure during external chest compression in pseudo-EMD, comparison of systolic versus diastolic synchronization.

BACKGROUND: The fraction of cardiac arrest patients presenting with pulseless electrical activity is increasing, and it is likely that many of these patients have pseudo-electromechanical dissociation (P-EMD), a state in which there is residual cardiac contraction without a palpable pulse. The efficacy of cardiopulmonary resuscitation (CPR) with external chest compression synchronized with the P-EMD cardiac systole and diastole has not been fully evaluated. HYPOTHESIS: During external chest compression in P-EMD, the coronary perfusion pressure (CPP) will be greater with systolic synchronization compared with diastolic phase synchronization. METHODS: A porcine model of P-EMD induced by progressive hypoxia with peak aortic pressures targeted to 50 mmHg was used. CPR chest compressions were performed by either load distributing band or vest devices. Paired 10s intervals of systolic and diastolic synchronization were performed randomly during P-EMD, and aortic, right atrial and CPP were compared. RESULTS: Stable P-EMD was achieved in 8 animals, with 2.6±0.5 matched synchronization pairs per animal. Systolic synchronization was association with increases in relaxation phase aortic pressure (41.7±8.9 mmHg vs. 36.9±8.2 mmHg), and coronary perfusion pressure (37.6±11.7 mmHg vs. 30.2±9.6 mmHg). Diastolic synchronization was associated with an increased right atrial pressure (6.7±4.1 mmHg vs. 4.1±5.7 mmHg). CONCLUSION: During P-EMD, synchronization of external chest compression with residual cardiac systole was associated with higher CPP compared to synchronization with diastole.

39-week toxicity and toxicokinetic study of ponezumab (PF-04360365) in cynomolgus monkeys with 12-week recovery period.

Ponezumab (PF-04360365) is a novel humanized IgG2Δa monoclonal antibody that binds to amyloid-ß (Aß). It is designed to have reduced immune effector function compared to other passive immunotherapies for Alzheimer's disease (AD). Toxicity was evaluated in cynomolgus monkeys treated intravenously with vehicle or 10, 30, or 100 mg/kg of ponezumab every 10th day for up to 39 weeks, and after a 12-week recovery phase. The Aß peptide sequence of monkeys is identical to that of humans. No substantial difference in test article exposure between sexes was observed, and mean plasma Cmax and AUC0-n were approximately dose-proportional. Ponezumab was detectable approximately 9 weeks after cessation of dosing. All animals, except two males given 10 mg/kg, maintained exposure to test article. One of these males tested positive for anti-ponezumab antibodies. Ponezumab was detected in the cerebrospinal fluid (CSF) of animals given active treatment. The estimated CSF/plasma ponezumab concentration ratio was <0.008 after multiple doses. At the end of the dosing and recovery phases, plasma Aß1-40 and Aß1-x were increased in treated animals versus controls. No test article-related effects were seen after ophthalmogical, cardiovascular, physical examinations, and clinical and anatomic pathology evaluations. Plasma concentrations of ponezumab on day 261 at the no observed adverse effect level of 100 mg/kg were 22.4 and 5.3 times greater on a Cmax and AUC basis, respectively, than human exposures at the highest dose (10 mg/kg) in a single-dose Phase I trial. These data suggest an acceptable safety profile for ponezumab as an immunotherapy for AD.

Comparison of defibrillation efficacy between two pads placements in a pediatric porcine model of cardiac arrest.

OBJECTIVE: The placement of defibrillation pads at ideal anatomical sites is one of the major determinants of transthoracic defibrillation success. However, the optimal pads position for ventricular defibrillation is still undetermined. In the present study, we compared the effects of two different pads positions on defibrillation success rate in a pediatric porcine model of cardiac arrest. METHODS: Eight domestic male pigs weighing 12-15 kg were randomized to receive shocks using either the anterior-posterior (AP) or the anterior-lateral (AL) position with pediatric pads. Ventricular fibrillation (VF) was electrically induced and untreated for 30 s. A sequence of randomized biphasic electrical shocks ranging from 10 to 100 J was attempted. If the defibrillation failed to terminate VF, a 100 J rescuer shock was then delivered. After a recovery interval of 5 min, the sequence was repeated for a total of approximately 30 test shocks were attempted for each animal. The dose response curves were constructed and the defibrillation thresholds were compared between groups. RESULTS: The aggregated success rate was 65.6% for AP placement and 43.0% for AL one (p=0.0005) when shock energy was between 10 and 70 J. A significantly lower 50% defibrillation threshold was obtained for AP pads placement compared with traditional AL pads position (2.1±0.4 J/kg vs. 3.6±0.9 J/kg, p=0.041). CONCLUSION: In this pediatric porcine model of cardiac arrest, the anterior-posterior placement of pediatric pads yielded a higher success rate by lowering defibrillation threshold compared to the anterior-lateral position.

The optimal phasic relationship between synchronized shock and mechanical chest compressions.

OBJECTIVE: Pauses for shock delivery in chest compressions are detrimental to the success of resuscitation and may be eliminated with the use of mechanical chest compressors. However, the optimal phasic relationship between mechanical chest compression and defibrillation is still unknown. We therefore undertook a study to assess the effects of timing of defibrillation in the mechanical chest compression cycle on the defibrillation threshold (DFT) using a porcine model of cardiac arrest. METHODS: Ventricular fibrillation was electrically induced and untreated for 10s in 8 domestic pigs weighing between 26 and 30 kg. Mechanical chest compression was then continuously performed for 25s, followed by a biphasic electrical shock which was delivered to the animal at 6 randomized coupling phases, including a control phase, with a pre-determined energy setting. The control phase was chosen at a constant 2s following discontinued chest compression. A novel grouped up-and-down DFT testing protocol was used to compare the success rate at different coupling phases. After a recovery interval of 4 min, the testing sequence was repeated, resulting in a total of 60 test shocks delivered to each animal. RESULTS: No difference between the delivered shock energy, voltage and current were observed among the 6 study phases. The defibrillation success rate, however, was significantly higher when shocks were delivered in the upstroke phase of mechanical chest compression. CONCLUSION: Defibrillation efficacy is maximal when electrical shock is delivered in the upstroke phase of mechanical chest compression.

Defibrillation delivered during the upstroke phase of manual chest compression improves shock success.

OBJECTIVE: The current standard of manual chest compression during cardiopulmonary resuscitation requires pauses for rhythm analysis and shock delivery. However, interruptions of chest compression greatly decrease the likelihood of successful defibrillations, and significantly better outcomes are reported if this interruption is avoided. We therefore undertook a prospective randomized controlled animal study in an electrically induced ventricular fibrillation pig model to assess the effects of timing of defibrillation on the manual chest compression cycle on the defibrillation threshold. DESIGN: Prospective, randomized, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Yorkshire-X domestic pigs (Sus scrofa). INTERVENTIONS: In eight domestic male pigs weighing between 24 and 31 kg, ventricular fibrillation was electrically induced and untreated for 10 secs. Manual chest compression was then performed and continued for 25 secs with the protection of an isolation blanket. The depth and frequency of chest compressions were guided by a cardiopulmonary resuscitation prompter. Animals were randomized to receive a biphasic electrical shock in five different compression phases with a predetermined energy setting. A control phase was chosen at a constant 2 secs after discontinued chest compression. A grouped up-down defibrillation threshold testing protocol was used to compare the success rate at different coupling phases. After a recovery interval of 4 mins, the sequence was repeated for a total of 60 test shocks for each animal. MEASUREMENTS AND MAIN RESULTS: No difference in coronary perfusion pressure before delivering of the shock was observed among the six study phases. The defibrillation success rate, however, was significantly higher when shocks were delivered in the upstroke phase of manual chest compression. CONCLUSION: Defibrillation efficacy is maximal when electrical shock is delivered during the upstroke phase of manual chest compression.

Individual effect of components of defibrillation waveform on the contractile function and intracellular calcium dynamics of cardiomyocytes.

OBJECTIVES: Although electrical shock is a unique and effective treatment for fatal arrhythmia, it produces myocardial dysfunction closely related to the intensity of shock delivered. The isolated contribution of defibrillator components to postshock contractile impairment is not yet securely established. We sought to evaluate contractile function in cardiomyocytes following electrical shocks with different peak currents, energies, and durations. We hypothesized that peak current may play a more important role than energy in determining postshock dysfunction. Prolongation of the duration may reduce contractile impairment. DESIGN: Prospective, randomized, controlled study. SETTING: University-affiliated research institute. SUBJECTS: Male albino Sprague-Dawley rats. INTERVENTIONS: We assigned 324 cardiomyocytes isolated from adult male rats to 11 groups having different waveforms (triangular and square), peak currents (derived from peak voltage gradients of 25 V/cm, 35.4 V/cm, 50 V/cm, 70.7 V/cm, and 100 V/cm), and durations (10 and 20 msecs) of shocks delivered. One single shock was given to each cardiomyocyte, and length shortening and Ca transients were recorded optically with fura-2 loading. MEASUREMENTS AND MAIN RESULTS: Increase of peak current and corresponding energy caused more cells to have irregular beating (p < .001) and reduced length shortening (p < .001). This was associated with increased Ca abnormality (p < .05). Increasing peak current independent of energy significantly impaired postshock contractile function (p < .05), whereas the change of energy alone did not. Prolongation of duration independent of energy and peak current reduced postshock contractile impairment (p < .05). CONCLUSIONS: Peak current may play a more determinative role in producing postshock contractile dysfunction than does energy.

Is the remodeling of the polyp prepattern in a hydrozoan planula a function of larval age or size and is it of "adaptive" significance?

Eggs of medusae develop into lecithotrophic planulae that undergo metamorphosis at different ages to form polyps. As planulae age they decrease in size as their yolk stores are utilized. The planulae of most Phialidium medusae develop into polyps where there is a decrease in the size of the holdfast region and a relative increase in the size of the hydranth region as they age. These changes occur independently of the decrease in planula size. In planulae with a decrease in the size of the holdfast region and an increase in the size of the hydranth-forming region there was a 50% decline in polyps that successfully stayed attached to the substrate after metamorphosis. These aged planulae produced an initial hydranth with the same number of tentacles as polyps from full-sized young planulae while young half-sized planulae produced hydranths where the tentacle number was smaller. The first phase of polyp colony growth with a small initial hydranth was slower than growth of a colony with a larger initial hydranth. Predation during this period led to more death in colonies with a small initial hydranth. The decline in successful attachment in aged planulae was not offset by the higher rate of growth and a smaller window of time where predation leads to death, suggesting that this age-related developmental change in planulae was not adaptive.

A new paradigm for human resuscitation research using intelligent devices.

OBJECTIVES: To develop new methods for studying correlations between the performance and outcome of resuscitation efforts in real-world clinical settings using data recorded by automatic devices, such as automatic external defibrillators (AEDs), and to explore effects of shock timing and chest compression depth in the field. METHODS: In 695 records of AED use in the pre-hospital setting, continuous compression data were recorded using AEDs capable of measuring sternal motion during compressions, together with timing of delivered shocks and the electrocardiogram. In patients who received at least one shock, putative return of spontaneous circulation (P-ROSC) was defined as a regular, narrow complex electrical rhythm > 40 beats/min with no evidence of chest compressions at the end of the recorded data stream. Transient return of spontaneous circulation (t-ROSC) was defined as the presence of a post-shock organized rhythm > 40 beats/min within 60s, and sustained > or = 30 s. 2x2 contingency tables were constructed to examine the association between these outcomes and dichotomized time of shock delivery or chest compression depth, using the Mood median test for statistical significance. RESULTS: The probability of P-ROSC for first shocks delivered < 50 s (the median time) after the start of resuscitation was 23%, versus 11% for first shocks > 50 s (p=0.028, one tailed). Similarly, the probability of t-ROSC for shorter times to shock was 29%, compared to the 15% for delayed first shocks (p=0.016). For shocks occurring > 3 min after initiation of rescue attempts, the probability of t-ROSC with pre-shock average compression depth > 5 cm was more than double that with compression depth < 5 cm (17.7% vs. 8.3%, p=0.028). For shocks > 5 min, the effect of deeper compressions increased (23.4% versus 8.2%, p=0.008). CONCLUSIONS: Much can be learned from analysis of performance data automatically recorded by modern resuscitation devices. Use of the Mood median test of association proved to be sensitive, valid, distribution independent, noise-resistant and also resistant to biases introduced by the inclusion of hopeless cases. Efforts to shorten the time to delivery of the first shock and to encourage deeper chest compressions after the first shock are likely to improve resuscitation success. Such refinements can be effective even after an unknown period of preceding downtime.

Electrocardiographic analysis during uninterrupted cardiopulmonary resuscitation.

OBJECTIVE: Prior studies have shown that interruptions of chest compressions could result in high failure rates of resuscitation. Chest compression artifacts force the interruption of compressions before electrocardiographic rhythm analysis. It was the goal of this study to evaluate the accuracy of an automated electrocardiographic rhythm analysis algorithm designed to attenuate compression-induced artifact and minimize uninterrupted chest compressions. DESIGN: Retrospective diagnostic analysis. SETTING: Out-of-hospital cardiopulmonary resuscitation. SUBJECTS: Eight hundred thirty-two patients. INTERVENTIONS: Patients were treated with defibrillation and cardiopulmonary resuscitation. Continuous data were recorded using automated external defibrillators with concurrent measurement of electrocardiographic and sternal motion during chest compressions. MEASUREMENTS AND RESULTS: Human electrocardiographics recorded by automated external defibrillators were annotated and randomly selected to build distinct training and testing databases. The artifact reduction and tolerant filter was applied to the electrocardiographic signal. The algorithm was optimized with the training database (sensitivity, 93.9%; specificity, 91.2%) and tested with the testing database (sensitivity, 92.1%; specificity, 90.5%). Average attenuation of compression-induced artifact was more than 35 dB. CONCLUSIONS: Shockable ventricular arrhythmias can be differentiated from electrocardiographic rhythms not requiring defibrillation in the presence of chest compression-induced artifact with sensitivity and specificity above 90%. With the artifact reduction and tolerant filter, it is possible to effectively eliminate pre- and postshock compression pauses.

Comparison of rectilinear biphasic waveform with biphasic truncated exponential waveform in a pediatric defibrillation model.

OBJECTIVE: To compare the rectilinear biphasic waveform with a biphasic truncated exponential waveform for pediatric defibrillation. DESIGN: Prospective, randomized study. SETTING: Experimental laboratory of a university-affiliated research institute. SUBJECTS: Male domestic piglets (4-24 kg). INTERVENTIONS: Eleven piglets (4-8 kg), which represented a patient <1 yr old, and ten piglets (16-24 kg), which represented a pediatric patient between the ages of 2 and 8 yrs, were anesthetized, intubated, and mechanically ventilated. Ventricular fibrillation was induced and maintained for 30 secs, and a predetermined shock was then delivered to defibrillate. Following defibrillation, the animal was permitted to stabilize hemodynamically for 4 mins. Fifty shocks were applied to each animal using a randomization schedule based on a predetermined permutation of 50. The 50 shocks were 25 shocks for each rectilinear biphasic and biphasic truncated exponential waveforms, comprising five shocks at five energy settings. Each group of five shocks was fixed at a predetermined energy value, depending on the body weight of the animal. Dose-response curves were constructed using logistic regression. Aortic pressure, electrocardiogram, left ventricular pressure, and left ventricular pressure value of 40 mm Hg were continually measured. MEASUREMENTS AND MAIN RESULTS: Dose-response curves determined defibrillation thresholds at 50% (D50) and 90% (D90) probability of success. The rectilinear biphasic waveform defibrillated with <90% of the D50 and D90 energies required for a biphasic truncated exponential waveform. The rectilinear biphasic waveform also successfully defibrillated with significantly less energy per body weight and per heart weight compared with a biphasic truncated exponential waveform. CONCLUSIONS: The rectilinear biphasic waveform has superior defibrillation performance compared with a biphasic truncated exponential waveform in a piglet defibrillation model for young children.

A developmental basis for the Cambrian radiation.

As extant bilaterian phyla emerged during the Lower Cambrian, these clades acquired morphological features that separated them from their stem groups. At the same time, morphological variants on the body plan within a phylum emerged that we recognize as classes and subphyla. In many cases, the emergence of body plan variants within a phylum is associated with major changes in patterns of early regional specification. Subsequently these different patterns of regional specification were stabilized, probably because later developmental events depended on them. As a consequence, the frequency of new body plan variants involving early development declined in these lineages at later periods during their history. This hypothesis is explicated here by examining the process of early regional specification in the different subphyla of brachiopods and in pairs of species from the same subphylum belonging to different clades that originated during the Jurassic, Ordovician, and Lower Cambrian.

Explaining the freemartin: Tandler and Keller vs. Lillie and the question of priority.

The correct explanation for the freemartin phenotype in the female twin of a female-male pair in cattle was first reported by Tandler and Keller (1911. Deutsche Tierärzt Wochenschr 19:148-149). This same explanation for the freemartin was independently discovered by Lillie (1916. Science 43:611-613). Today both set of scientists are given credit for this discovery; it is the basis for much of the subsequent work on the developmental basis for sex differentiation in vertebrates. Even though Lillie published after Keller and Tandler, he gets credit for this discovery because: (1) Keller and Tandler published in a veterinary journal and as a consequence their work was not disseminated as broadly throughout the larger scientific community; this problem was compounded by the fact that their definitive 1916 paper was published under wartime conditions during World War I, and (2) Lillie was an influential scientist with a group of graduate students who could elaborate on and extend his work; they published a number of papers on the freemartin. At some point while Lillie was doing his initial work on the freemartin he may have become aware that Keller and Tandler were also working on the freemartin problem; this information may have shaped his decision on when to publish.