634 research outputs found

    The Forces Applied by Cilia Depend Linearly on Their Frequency Due to Constant Geometry of the Effective Stroke

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    AbstractMucus propelling cilia are excitable by many stimulants, and have been shown to increase their beating frequency up to threefold, by physiological extracellular stimulants, such as adenosine-triphosphate, acetylcholine, and others. This is thought to represent the evolutionary adaptation of mucociliary systems to the need of rapid and efficient cleansing the airways of foreign particles. However, the mucus transport velocity depends not only on the beat frequency of the cilia, but on their beat pattern as well, especially in the case of mucus bearing cilia that beat in a complex, three-dimensional fashion. In this study, we directly measured the force applied by live ciliary tissues with an atomic force microscope, and found that it increases linearly with the beating frequency. This implies that the arc swept by the cilia during their effective stroke remains unchanged during frequency increase, thus leading to a linear dependence of transport velocity on the beat frequency. Combining the atomic force microscope measurements with optical measurements, we have indications that the recovery stroke is performed on a less inclined plane, leading to an effective shortening of the overall path traveled by the cilia tip during this nontransporting phase of their beat pattern. This effect is observed to be independent of the type of stimulant (temperature or chemical), chemical (adenosine-triphosphate or acetylcholine), or concentration (1ÎŒM–100ÎŒM), indicating that this behavior may result from internal details of the cilium mechanical structure

    Does modifying the thick texture and creamy flavour of a drink change portion size selection and intake?

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    Previous research indicates that a drink's sensory characteristics can influence appetite regulation. Enhancing the thick and creamy sensory characteristics of a drink generated expectations of satiety and improved its actual satiating effects. Expectations about food also play an important role in decisions about intake, in which case enhancing the thick and creamy characteristics of a drink might also result in smaller portion size selection. In the current study forty-eight participants (24 female) completed four test days where they came into the laboratory for a fixed-portion breakfast, returning two hours later for a mid-morning drink, which they could serve themselves and consume as much as they liked. Over the test days, participants consumed an iso-energetic drink in four sensory contexts: thin and low-creamy; thin and high-creamy; thick and low-creamy; thick and high-creamy. Results indicated that participants consumed less of the thick drinks, but that this was only true of the female participants; male participants consumed the same amount of the four drinks regardless of sensory context. The addition of creamy flavour did not affect intake but the thicker drinks were associated with an increase in perceived creaminess. Despite differences in intake, hunger and fullness ratings did not differ across male and female participants and were not affected by the drinks sensory characteristics. The vast majority of participants consumed all of the drink they served themselves indicating that differences in intake reflected portion size decisions. These findings suggest women will select smaller portions of a drink when its sensory characteristics indicate that it will be satiating

    Representations on Hessenberg Varieties and Young's Rule

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    We combinatorially construct the complex cohomology (equivariant and ordinary) of a family of algebraic varieties called regular semisimple Hessenberg varieties. This construction is purely in terms of the Bruhat order on the symmetric group. From this a representation of the symmetric group on the cohomology is defined. This representation generalizes work of Procesi, Stembridge and Tymoczko. Here a partial answer to an open question of Tymoczko is provided in our two main result. The first states, when the variety has multiple connected components, this representation is made up by inducing through a parabolic subgroup of the symmetric group. Using this, our second result obtains, for a special family of varieties, an explicit formula for this representation via Young's rule, giving the multiplicity of the irreducible representations in terms of the classical Kostka numbers

    A Divided Difference Operator

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    We construct a divided difference operator using GKM theory. This generalizes the classical divided difference operator for the cohomology of the complete flag variety. This construction proves a special case of a recent conjecture of Shareshian and Wachs. Our methods are entirely combinatorial and algebraic, and rely heavily on the combinatorics of root systems and Bruhat order

    Modelling mucociliary clearance

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    Mathematical modelling of the fluid mechanics of mucociliary clearance (MCC) is reviewed and future challenges for researchers are discussed. The morphology of the bronchial and tracheal airway surface liquid (ASL) and ciliated epithelium are briefly introduced. The cilia beat cycle, beat frequency and metachronal coordination are described, along with the rheology of the mucous layer. Theoretical modelling of MCC from the late 1960s onwards is reviewed, and distinctions between ‘phenomenological’, ‘slender body theory’ and recent ‘fluid–structure interaction’ models are explained.\ud \ud The ASL consists of two layers, an overlying mucous layer and underlying watery periciliary layer (PCL) which bathes the cilia. Previous models have predicted very little transport of fluid in the PCL compared with the mucous layer. Fluorescent tracer transport experiments on human airway cultures conducted by Matsui et al. [Matsui, H., Randell, S.H., Peretti, S.W., Davis, C.W., Boucher, R.C., 1998. Coordinated clearance of periciliary liquid and mucus from airway surfaces. J. Clin. Invest. 102 (6), 1125–1131] apparently showed equal transport in both the PCL and mucous layer. Recent attempts to resolve this discrepancy by the present authors are reviewed, along with associated modelling findings. These findings have suggested new insights into the interaction of cilia with mucus due to pressure gradients associated with the flat PCL/mucus interface. This phenomenon complements previously known mechanisms for ciliary propulsion. Modelling results are related to clinical findings, in particular the increased MCC observed in patients with pseudohypoaldosteronism. Recent important advances by several groups in modelling the fluid–structure interaction by which the cilia movement and fluid transport emerge from specification of internal mechanics, viscous and elastic forces are reviewed. Finally, we discuss the limitations of existing work, and the challenges for the next generation of models, which may provide further insight into this complex and vital system

    Do Alternative Dispute Resolution (ADR) and track two processes support transboundary marine conservation? Lessons from six case studies of maritime disputes

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    By definition, marine protected areas (MPAs) and other effective area-based conservation measures (OECMs) address spatial aspects of the ecological processes and marine features. Such a requirement is especially challenging in areas where there is no clearly defined jurisdiction. However, in these areas, assigning sovereignty and rights can be achieved through bilateral or multilateral agreements, or with the use of alternative dispute resolution (ADR) tools such as mediation and arbitration. In some cases, states may engage in transboundary marine conservation initiatives to provide an entry point to enable wider collaboration. These processes can also evolve into a form of ‘environmental peacebuilding’ while ideally maintaining ecosystem functioning and resilience as a core goal. Conversely, MPAs and OECMs can also be used to assert maritime sovereignty rights over disputed waters, under the pretext of conserving marine habitats. This paper identifies emerging issues of conflict resolution and their interaction with transboundary marine conservation. While ADR focuses on negotiations and facilitated processes between state representatives (“track one diplomacy”), we also discuss other forms and levels of marine environmental peacebuilding and dispute resolution, particularly those between civil society organizations (“track two diplomacy”). The six case studies presented highlight areas of recent maritime conflict or border disputes in the Mediterranean Sea, the Red Sea, the West Indian Ocean, the Korean West Sea and the South China Sea. In all cases, high ecological value, vulnerable ecosystems, and the need to conserve ecosystem services provide a shared interest for cooperation despite on-going diplomatic difficulties. The strategies used in these cases are analyzed to determine what lessons might be learned from cross-border collaborative marine initiatives in situations of territorial dispute. The use of ADR tools and their ability to support joint marine initiatives are examined, as well as how such initiatives contribute to formal border negotiations. Other forms of inter-state dialogue and cooperation between local or civil organizations, circumventing formal treaties and negotiations between state leaders (‘track two’) are also investigated. Finally, other influencing factors, including third-party involvement, stakeholder interests, power dynamics, economic context, and socio-cultural aspects, are considered.European Cooperation in Science and Technology (COST):15121info:eu-repo/semantics/publishedVersio

    Speaking with different voices: the problems with English law and psychiatric injury

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    Private law courts in the UK have maintained the de minimis threshold as a condition precedent for a successful claim for the infliction of mental harm. This de minimis threshold necessitates the presence of a ‘recognised psychiatric illness’ as opposed to ‘mere emotion’. This standard has also been adopted by the criminal law courts when reading the Offences Against the Person Act 1861 to include non-physical injury. In determining the cut-off point between psychiatric injury and mere emotion, the courts have adopted a generally passive acceptance of expert testimony and the guidelines used by mental health professionals to make diagnoses. Yet these guidelines were developed for use in a clinical setting, not a legal one. This article examines the difficulty inherent in utilising the ‘dimensional’ diagnostic criteria used by mental health professionals to answer ‘categorical’ legal questions. This is of particular concern following publication of the new diagnostic manual, DSM-V in 2013, which will further exacerbate concerns about compatibility. It is argued that a new set of diagnostic guidelines, tailored specifically for use in a legal context, is now a necessity

    Acute alcohol consumption disrupts the hormonal milieu of lactating

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    Abstract Despite the lack of scientific evidence to support the claim that alcohol is a galactagogue, lactating women have been advised to drink alcohol as an aid to lactation for centuries. To test the hypothesis that alcohol consumption affects the hormonal response in lactating women, we conducted a withinsubjects design study in which 17 women consumed a 0.4 g/kg dose of alcohol in orange juice during one test session and an equal volume of orange juice during the other. Changes in plasma prolactin, oxytocin, and cortisol levels during and after breast stimulation, lactational performance, and mood states were compared under the two experimental conditions. Oxytocin levels significantly decreased, whereas prolactin levels and measures of sedation, dysphoria, and drunkenness significantly increased, during the immediate hours after alcohol consumption. Changes in oxytocin were related to measures of lactational performance such as milk yield and ejection latencies, whereas changes in prolactin were related to self-reported measures of drunkenness. Although alcohol consumption resulted in significantly higher cortisol when compared with the control condition, cortisol levels were not significantly correlated with any of the indices of lactational performance or self-reported drug effects. Moreover, cortisol levels steadily decreased on the control day, indicating that the procedures were not stressful to the subjects. In conclusion, recommending alcohol as an aid to lactation may be counterproductive. In the short term, mothers may be more relaxed, but the Correspondence to: Julie A. Mennella. Address all correspondence and requests for reprints to: Julie A. Mennella, Ph.D., 3500 Market Street, Philadelphia, Pennsylvania 19104-3308. E-mail: [email protected] hormonal milieu underlying lactational performance is disrupted, and, in turn, the infant's milk supply is diminished. THE TRADITIONAL WISDOM of many cultures relates that women can optimize the quality and quantity of their milk to meet the needs of their infants through diet and psychological well-being. Each culture claims some milk-producing (galactogenic) substances, and many cultures claim alcohol to be such a substance (1). Such beliefs were so ingrained in American tradition that, in 1895, Anheuser-Busch Company, a major U.S. brewery, produced MaltNutrine, a low-alcoholic beer that was sold exclusively in drugstores and prescribed by physicians as a tonic for pregnant and lactating women (2). Even in more modern times, a popular book for nursing mothers hailed the virtues of alcohol as a galactagogue, claiming ". . . this is one time in life when the therapeutic qualities of alcohol are a blessing " (3). Such claims have not gone unchallenged. In 1987, the Journal of the American Medical Association published a letter from a physician asking whether there was any scientific basis for prescribing a daily beer to lactating women (4). The scientific basis, it was declared (5), can be found in the finding that the consumption of beer, unlike other alcoholic beverages, increases serum prolactin (5,6). There are several problems with this conclusion, however. First, the subjects in these research studies were men and nonlactating women. No study to date had examined the effects of alcohol consumption on the hormonal milieu of lactating women, additionally highlighting the lack of evidence-based practice related to recommendations regarding alcohol consumption during lactation. There has been considerable research in animal models (for review, see Ref. 7), however. Although the vast majority of these studies reported that ethanol administration decreased suckling-induced prolactin, the most recent study, which extended the observation period Second, the rise in prolactin levels after alcohol consumption was observed after the consumption of different types of alcoholic beverages (9,10) and was not specific to beer consumption, as the folklore suggested (2,4,5). Moreover, if alcohol does indeed increase prolactin levels in maternal circulation, it is not apparent whether such increases affect lactational performance. Although prolactin appears to be essential for the initiation of lactation and its maintenance in the long term (11), no clear temporal correlation exists between plasma prolactin levels and milk yield of a particular breastfeed in humans (12). Third, it is perplexing that one would argue that alcohol enhances lactational performance when this same drug, at similar or slightly higher doses, was used in the not-so-distant past to treat premature labor Fourth, research conducted during the past decade refutes the lore that alcohol is a galactagogue. Rather, lactating mothers produced less milk without changes in the caloric content of their milk (16), and, in turn, infants consumed less breast milk and less calories during the immediate hours after maternal consumption of beer as well as other types of alcoholic beverages NIH-PA Author Manuscript The present study tested the hypothesis that the alcohol-induced depression in milk production in lactating women was due to disruptions in the hormonal milieu. Oxytocin and prolactin responses were evaluated when lactating women consumed a moderate dose of alcohol, one that was equivalent to one to two drinks and represents the average amount of alcohol lactating women reported consuming during a drinking occasion (20). Subjects and Methods Subjects Seventeen nonsmoking, healthy lactating women (six primiparous and 11 multiparous), who were exclusively nursing infants between the ages of 2 and 4 months, were recruited from ads in local newspapers and newsletters. One additional woman began testing but was excluded because of procedural difficulties. During initial screening, women were excluded if they were lifetime alcohol abstainers, on any medication including oral contraceptives, or had resumed menstruation, because there is some suggestion that both basal and peak prolactin levels are lower in such women (21). All procedures were approved by the Office of Regulatory Affairs at the University of Pennsylvania, and each subject gave informed written consent before testing. The women (10 Caucasian, five African American, one Asian, and one from another ethnic group) were, on average, 31.9 ± 1.2 yr of age, with a mean body mass index of 26.4 ± 1.1 kg/ m 2 . They reported that alcohol intake was low during pregnancy (mean = 0.2 ± 0.1 standard drinks per month) but significantly increased to, on average, 1.5 ± 0.6 drinks per month during lactation [paired t-test (16df) = -2.14; P = 0.048]. These numbers likely underestimate alcohol usage (22). Procedures A within-subjects design study that controlled for time of day was employed because milk composition and hormonal responses vary throughout the day. Using methodologies developed for the study of neurally mediated hormonal responses in humans (23), women were tested at the General Clinical Research Center (GCRC) at the University of Pennsylvania on 2 d separated by 1 wk (±2 d). After abstaining from alcohol for at least 3 d, all subjects arrived at the GCRC at 0800 h (±30 min) after an overnight fast and remained fasted during the entire testing procedures, because prolactin levels can be potentiated by certain gastrointestinal hormones and high blood glucose levels (24). Mothers were not allowed to watch television, sleep, or talk, as well as read about food or infants throughout the entire testing session because these behaviors may affect the hormones under study. Instead, they were able to read magazines or novels or to converse on other topics. Moreover, infants were not present because the mere sound, sight, or smell of the baby often stimulates milk let-down or leaking (25). Breast stimulation was provided by an electric breast pump because prior work revealed that infants â€Č sucking intensity changes when their mothersâ€Č milk contains alcohol (20). Approximately 30 min after arrival, an iv line was inserted into the antecubital vein of an arm. Because prolactin is very stress labile and rises during the first half-hour after a needle prick (26), subjects acclimated in a private testing room for 45 min. After acclimatization, blood samples were obtained at fixed intervals (-40, -25, and -10 min) before drinking a 0.4 g/kg dose of alcohol in orange juice (15% vol/vol) on one testing day (alcohol condition) and an equal volume of orange juice on the other day (control condition). During both conditions, 3 ml of alcohol were pipetted onto the surface of the cup to serve as a smell and flavor mask (27). The order of testing was randomized between subjects. The beverage was aliquoted into two equal volumes, and each aliquot was consumed within consecutive 5-min periods. As shown in Blood alcohol concentrations (BAC; g/liter) were estimated by having subjects breathe into an Alco-Sensor III (Intoximeters, Inc., St. Louis, MO) throughout the test sessions ( Hormone assays Plasma samples were measured in duplicate by double-antibody RIAs for oxytocin and cortisol and by immunoradiometric assay for prolactin. Standards were run with each assay. All samples from a given subject from both days (alcohol and control) of testing were run within the same assay to reduce interassay variability. Cortisol levels were monitored on the control day to ensure that alterations in hormonal responses were not related to the stress of the procedures (10). Intraassay variation was 2.8, 3.0, and 1.3%, and interassay variation was 1.9, 8.9, and 10.2% for oxytocin, prolactin, and cortisol, respectively. All assays were performed by the Diabetes Research Center of the University of Pennsylvania. Oxytocin was assayed without extraction by using a competitive RIA, with materials supplied by Phoenix Pharmaceuticals, Inc. (Belmont, CA). The antiserum cross-reactivity with arginine vasopressin, GH, α-atrial natriuretic peptide (1-28), methionine-enkephalin, GH-releasing factor, somastatin, TRH, vasoactive intestinal peptide, and pituitary adenylate cyclaseactivating polypeptide 27-NH 2 is 0%. The minimal detectable concentration was 10 pg/ml (8 pmol/liter). Prolactin was assayed by a direct, two-site immunoradiometric assay without extraction, using materials supplied by ICN Diagnostics (Costa Mesa, CA). The antiserum cross-reactivity is less than 0.01% for human chorionic gonadotropin, TSH, LH, and FSH. The minimal detectable concentration was 2.5 ng/ml (108.8 pmol/liter). Cortisol was measured without extraction by a competitive double-antibody RIA kit from ICN Diagnostics. The antiserum cross-reacts 12.3% with 11-deoxycortisol, 5.5% with corticosterone, and less than 2.7% with all other steroids tested. Data analyses Separate repeated measures mixed ANOVA were conducted to determine whether there were significant differences in prolactin, oxytocin, cortisol, and BAC levels, as well as various measures of self-reported drug effects with experimental condition (alcohol and control) and time as the within-subjects factors. When significant, post hoc Fisher least significant difference analyses were conducted. Because there were no significant differences in the basal values for oxytocin [F(2,32df) = 2.17; P = 0.13] and prolactin [F(2,32df) = 0.50; P = 0.61], we calculated changes in prolactin and oxytocin from respective baseline value (mean of three baseline samples) for each subject. There was a significant effect of time on cortisol baseline samples [F(2,32df) = 60.77; P < 0.0001]. Therefore, the last sample (t =-10 min) was used as the baseline value. We then determined the peak value for each hormone when compared with baseline and calculated the area under the curve (AUC) values by using a point-to-point method (OriginLab Corporation, Northampton, MA) from baseline to the end of the test session (t = 140 min). The areas for each hormone and for each subject were calculated independently. Paired t-tests were used to compare the peak value of each hormone and the AUC between experimental conditions, respectively. The critical value for significance was P < 0.05, and all P values represent two-tailed tests. Results Hormonal responses and lactational performance Oxytocin. There was a significant interaction between condition and time on oxytocin levels [F(15,240df) = 1.83; P = 0.03]. As shown in Although there were no significant correlations with oxytocin AUC during breast stimulation and milk ejection latency Twelve of the 17 women produced less oxytocin during breast stimulation on the alcohol day when compared with the control day (P < 0.05). These women also had lower milk yields during the 16 min of pumping when compared with the remaining women [F(1,15df) = 9.35; P = 0.008]. They produced, on average, 13 ± 7% less milk during these 16 min of pumping (control vs. alcohol, 131 ± 10 vs. 113 ± 11 ml). There were no significant relationships between the oxytocin AUCs or oxytocin levels on either the control or alcohol day and any of the selfreported measured indices of drug effects (all P values >0.10). Prolactin. There was a significant interaction between condition and time on prolactin plasma levels [F(15,240df) = 3.31; P < 0.001]. As shown in NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript = 3.52; P = 0.003]. This enhanced response was observed in 76% of the women tested (P = 0.02). Although there were no significant relationships on the control day between prolactin levels and milk ejection latency or amount of milk expressed (all P values > 0.10), prolactin AUCs during breast stimulation were significantly correlated with milk ejection latencies on the day women consumed alcohol ( Cortisol. Although the repeated measure mixed ANOVA analysis revealed only a tendency for an interaction effect between condition and time for cortisol levels [F(15,240df) = 1.63; P = 0.07], there were significant effects of condition [F(1,16df) = 5.91; P = 0.03] and time [F (15,240df) = 4.39; P < 0.001] on cortisol levels. As shown in Ethanol pharmacokinetics and self-reported drug effects BAC peaked approximately 43-51 min after alcohol consumption and decreased thereafter. As shown in Discussion Moderate alcohol consumption disrupted the two key hormones underlying lactational performance. During the immediate hours after alcohol consumption, oxytocin levels significantly decreased, whereas prolactin levels significantly increased both during and after breast stimulation. The magnitude and persistence of the hormonal response in lactating women is more robust when compared with men and nonlactating women (5,6,9,10), further highlighting the dynamics of the system under study. The diminished oxytocin response was significantly related to decreases in milk yield and milk ejection. These latter findings suggest that such changes in hormonal responses mediate the diminished milk production by lactating women (16) and disruption in their infantsâ€Č suckling behaviors and milk intake observed in prior research In contrast to the response observed for oxytocin, prolactin levels significantly increased after alcohol consumption both during and after periods of breast stimulation. The alcohol-induced increases in prolactin were related to self-reported perceptions of drunkenness. Women also reported increased feelings of sedation and dysphoria during the immediate hours after alcohol consumption. Because sleep deprivation increases feelings of sedation and dysphoria (32), we hypothesize that sleep deprivation, which is common among mothers of young infants, contributed to the increased feelings of sedation and dysphoria observed on the day lactating women consumed alcohol, as discussed herein. Although prolactin levels during breast stimulation were related to milk ejection latency on the day women consumed alcohol, it should be emphasized that no relationships were observed between prolactin levels or AUCs and the amount of milk produced on either test day. This is consistent with prior research revealing that although prolactin appears to be essential for the initiation of lactation and its maintenance in the long term (11), no clear temporal correlation exists between plasma prolactin levels and milk yield of a particular breastfeed in humans (12). It remains to be determined whether the relationship between alcohol-induced changes in prolactin and milk ejection latency was a spurious correlation and secondary to the effect of alcohol on other mediating factors underlying ejection. Cortisol levels were also increased during the test session in which women consumed the alcoholic beverage, a finding that is consistent with research from animal models (33) and some human studies (34). However, such changes in cortisol were not related to changes in oxytocin or prolactin, measures of lactational performance, or mood states. The production, secretion, and ejection of milk are the result of highly synchronized endocrine and neuroendocrine processes, which are governed, in part, by the frequency and intensity of the infantsâ€Č sucking. Breast stimulation resulted in transient release of both oxytocin and prolactin to levels previously observed by other researchers (35). Although these two key hormones usually behave in tandem under normal conditions, alcohol consumption resulted in differential and divergent responses. We hypothesize that alcohol acts at the central nervous system level through a general depression or by inhibiting synaptic transmission of afferent impulses to the hypothalamus. Such depression or inhibition would decrease oxytocin levels (36), but, because projections from the hypothalamus exert an inhibitory control of prolactin, prolactin levels would increase (37). Whether the enhanced prolactin response is also due to alcoholâ€Čs simulation of extrapituitary tissues such as the mammary glands (38), which are capable of producing prolactin, is not yet known. Animal studies suggest that alcohol, directly or indirectly via estrogens, may elevate prolactin by stimulating activity of lactotropes in the adenohypophysis (38). Recent studies indicate that one fourth of the women surveyed reported that they were encouraged by health professionals to drink once they began lactating (1,39). Advice ranged from the recommendation that drinking alcohol shortly before nursing will facilitate let-down and milk production to the belief that by drinking such milk, the infant will relax, become less "colicky," and obtain warmth. Some health professionals promote moderate drinking (1,39), whereas others caution that extremely high doses (≄1.0 g/kg) inhibit the milk ejection reflex (40). The present findings, which employed more sensitive measures and controls than research conducted in the 1960-1970s (15), revealed that lower doses of alcohol have similar effects on hormonal milieu and lactational performance. Several explanations, not mutually exclusive, may shed light on why the folklore that alcohol consumption enhances lactational performance has persisted for centuries. First, because difficulties with lactational performance are often attributed to stress, alcohol is then prescribed as an aid to lactation because of its anxiolytic and sedative properties. The present study revealed that relatively low BACs produce slight, but significant, alterations in feelings of drunkenness, dysphoria, and sedation. However, paralleling these mood changes are disruptions in the hormonal milieu that may impair lactational performance. Second, the lactating mother does not have an immediate means of assessing milk yield or intake. Although breast-fed infants consumed, on average, 20% less milk after mothersâ€Č consumption of the Mennella et al
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