Hepatitis C virus (HCV) infections are a severe burden on public health worldwide, causing mortality rates triple that of the general population. Since 2011, for both therapy-naive and therapy-experienced genotype 1 patients, the first generation of direct acting antivirals (DAAs), i.e., the protease-inhibitors (PI) telaprevir and boceprevir have been added to existing dual therapies. The therapeutic effect of the resulting triple therapy is striking; however, treatment regimens are complex and commonly cause side effects. Little is known of how patients implement therapy in their daily lives, or of how they deal with these effects.This study aims to describe HCV patients' experiences with protease-inhibitor-based triple therapy and their support needs.A qualitative design was used. Patients from three outpatient clinics, with ongoing, completed or discontinued PI treatment experience were recruited using a maximum variation sampling approach. Open-ended interviews were conducted and analyzed using thematic analysis according to Braun & Clarke .Thirteen patients participated in the interviews. All described themselves as highly motivated to undergo treatment, since they saw the new therapy as a “real chance” for a cure. However, all later described the therapy period as a struggle. The constitutive theme–“Fighting an uphill battle”– describes the common existential experience of and negative consequences of coping with side effects. The processes that fostered this common experience followed three sub-themes: “encountering surprises”, “dealing with disruption” and “reaching the limits of systems”.HCV patients undergoing outpatient protease-inhibitor-based triple therapy need systematic support in symptom management. This will require specially trained professionals to advise and support them and their families, and to provide rapid responses to their needs throughout this complex course of therapy. As the generation of DAAs for all genotypes, are expected to have less severe side effects, and many HCV patients require treatment, this knowledge can improve treatment support tremendously, especially for patients who are quite difficult to treat. Furthermore, these findings are helpful to illustrate development in HCV treatment.The online version of this article (doi:10.1186/1471-2334-14-507) contains supplementary material, which is available to authorized users. Hepatitis C virus (HCV) infections are a severe burden on public health worldwide. As the main causes of cirrhosis and cancer of the liver, they are the most frequent indication for liver transplantation , 2. It iAntiviral therapies' sustained virological response (SVR), indicating that the patient is cured, is defined as the absence of target virus RNA 24 weeks after the end of therapy . For morHCV care is usually performed in outpatient clinics. This presumes that patients who start treatment are capable of taking oral medication linked to dietary requirements, e.g., TPV along with 21 grams of fat, and self-administering subcutaneous injections at least twice daily. With triple therapy, in order to prevent resistance, the protease-inhibitor must be taken punctually three times a day, i.e., every 8 hours . MoreoveSide effects of anti-HCV dual therapy can include flu-like symptoms, fatigue, depression, skin problems or changes in blood counts . Under tThe complexity of the treatment plan and dealing with various symptoms of the disease and its treatment places great self-management demands on the patient. By definition, self-management encompasses the day-to-day activities a chronically ill patient performs to minimize the negative consequences of his or her condition. Such actions vary based on the persons’ perceptions, experiences and expertise, but share the focus of optimizing health outcomes and improving overall wellness , 20. DurSide effects are additional challenges and have been shown to negatively impact treatment adherence , 29. PreSo far, though, little is known about how patients implement triple therapy in their everyday lives and how they deal with side effects . To enabA qualitative research approach was selected for the description of patients’ triple therapy experiences. This is appropriate when prior knowledge and empirical evidence are limited and understanding of patients’ perspectives is needed to develop culturally sensitive instruments and effective interventions . MethodoThe study was performed between October 2012 and February 2013 in three outpatient clinics: an infectious disease clinic and a gastroenterological/hepatological clinic, both at the same hospital, and a clinic for internal medicine and infectious diseases at a center for addiction medicine. This multicenter approach was chosen because few patients were being treated with triple therapy at the time of investigation. The aim was to recruit 10 – 15 patients–a number usually sufficient to provide meaningful insights into patient experiences through the identification of themes reflecting commonalities and differences. Inclusion criteria were: being 18 years of age or older, having four weeks or more experience with a protease-inhibitor-based HCV therapy , being in outpatient medical care and having the ability to participate in an interview in German. Persons whose treating physicians judged the additional burden of study participation unacceptable in relation to their emotional state  were excluded. Recruitment used maximum variation sampling . The priPatients were informed about the study either during a medical check-up visit or by telephone by a healthcare provider whom they knew. Of the 15 persons contacted about the study, 13 agreed to participate. Of the reasons for refusal, one patient's travel plans conflicted with the study timetable and the other did not wish to spend the necessary time participating.Data collection was performed via open-ended interviews. Prior to the study, guidelines were developed with open questions on experiences concerning illness, treatment, symptoms and interactions with significant others, including healthcare providers. For all participants the interview started with the following open question: “Would you please tell me about your day-to-day experience with hepatitis C treatment?” Based on the patient’s narratives, mentioned topics were explored in depth. The interviewer asked about any topics listed in the interview guide but not brought up by patients. Data analysis was started after the first three interviews.Throughout the study, we continuously integrated and discussed themes from preliminary analysis to identify commonalities and differences between participants. Following Thorne's position that being able to explore all possible theoretical aspects of a phenomenon is useful in the discovery of basic social processes, but is less logical in documenting human health experience  , we did The first author (MR), an experienced addiction medicine and infectious diseases nurse and Master’s student, conducted the interviews. She was supervised by the last author (DN), an experienced qualitative researcher. She did not provide nursing care for any of the participants.The participants decided on the locations for their interviews. Four were conducted at home and nine in the hospital after a medical consultation. At one interview a 2-year-old child was present; at another the patient’s partner attended to fill in the gaps in her partner’s memory during a life-threatening episode. Otherwise, only the interviewer and the participant were present. The interviews lasted 30–64 minutes (mean: 45 minutes), and were recorded and transcribed verbatim, omitting the patient’s or any other names, as well as the place of interview. Transcripts were not returned to patients for comment.After the open-ended interviews, sociodemographic and medical data were collected using a structured questionnaire , PI used, residence situation, occupation, ability to work). Field notes were also made after each interview.The transcripts were systematically analyzed according to the thematic analysis method described by Braun and Clarke . This prAfter data analysis was finalized, results were translated into English by a professional translator. The translation was checked and adapted by the research team. Very specific difficult-to-translate wordings were added in parentheses in the language of origin.The 15-item criteria checklist developed by Braun und Clarke  was usedOf the eight men and five women who participated in the study (aged 36–63 years), eight were living with partners or family, three alone and two in an institution. Their HCV diagnoses had been made 1.5 – 28 years previously. Before starting triple therapy, twelve of thirteen patients had experienced fibrosis stages that indicated treatment. Eight had prior experience with dual therapy and five had none. For their triple therapy, the PI Telaprevir had been administered to nine persons and Boceprevir to four. Demographic and medical data are presented in Table Participants' stories revealed that before starting triple therapy, all believed that, because of the condition of their liver, the recommended treatment was necessary to improve or maintain their health long-term. Perceiving no alternatives, but considering the new triple therapy a “real chance” to overcome the disease, they had chosen to undergo therapy. This decision was strengthened by the knowledge that treatment time would be limited. Prior to the treatment trial's commencement, all had rated it as worth a try. One woman, for example, compared the trial to her HIV therapy:I also think it’s good that it only lasts a year and not like in HIV. For that, you have to take it forever. I’ll push it through for a year, even if it’s not pleasant, as long as it does some good. If it doesn’t do any good, then it’s logical that I wouldn’t. Despite their high initial levels of motivation, all test patients later found themselves struggling to continue with the therapy, which was physically, emotionally and socially draining, and which dominated their everyday lives. The constitutive theme characterizing this experience is “Fighting an uphill battle”. This common experience was fostered by a process described by three sub-themes: “encountering surprises”, “dealing with disruption” and “reaching the limits of systems” During this trying time, patients were additionally confronted with the limits of the support available from healthcare professionals, family and friends. Amplified by health-threatening and even life-threatening experiences, patients described everyday life as defined by existential battles against innumerable side effects, which started for some immediately and for others later in the course of treatment. In analogy to their experience they used a battle language. For example, patients described that they fought against symptoms or experienced “hell-fire”. In addition to physical and emotional burdens, patients experienced social limitations, even to the point of isolation. One woman  said she felt half dead during therapy – a “zombie” with no influence on anything and no idea what was happening to her. The symptoms affected many very strongly. For example, they “hit rock bottom”, were “broken on the wheel”, “run over by a truck”, “put through the mill”, or “forced to crawl on all fours”. And the effects could come on very quickly: one had to be admitted to an emergency room “out of the blue”. Those who suffered the most pronounced symptoms agreed that simply maintaining one's course demanded tremendous strength and discipline. Against this stream of suffering, only the hope of a cure drove them onward. One man said:And then I battled the rash and told myself that I would carry on, heaven knows how, but I simply would not fail. The ever-present feeling of “fighting an uphill battle” which beset the patients was amplified by the fact that, despite the information they had received, their symptoms surpassed their imagination.The patients reported that prior to the beginning of therapy, HCV healthcare providers had informed them of side effects they might perceive to varying degrees. Therefore, all expected unpleasant and undesirable symptoms. Based on experience with other medications, including dual therapy, some expected similar symptoms, while others expected greater difficulties from the start. For most, however, the symptoms surpassed all expectations and were unexpected despite preparation. One woman described this as follows:Actually, I worked the whole time during the first therapy, yet I can’t remember exactly, but it was never, ever in the way, never to the extent [of the triple therapy side effects], not the icy cold and the drying out, not all that hair loss, either. That’s why I was shocked. Often the patients lacked the specific vocabulary to denote their symptoms, reporting that they would be difficult to explain to anyone who had never experienced them. Instead, they used vivid descriptions, such as “freezing torpor”, ”frozen skeleton”, “looking like a spotty monster”, “moving like a robot”, wanting to “get the carving knife and scrape that stuff off”, “having the feeling of consisting only of tablets”. Their healthcare providers seemed not to have sufficient experience with other patients to help with finding language. For several participants the symptoms were often so numerous that the burden of suffering could barely be borne. One man described it as follows:Life at the moment is only the fight against side effects. Hardly over the worst of one, and up comes the next already. There were maybe four or five most difficult things which were really stressful, and then there were another 20, 30 minor things, like mental problems, difficulties going out among people, suddenly being easily frightened and uncertain. I’m not otherwise a person who lacks self-confidence. Yes, there are a lot of such things. Even patients with fewer side effects said many of them were agonizing. Also, because symptoms often arose with great speed and force, and the patients lacked any related experiences, they had few strategies for dealing with them. One woman said:The side effects were very severe, in particular depression was heavy. What was worst was that it started right away, that everywhere there is mucosa hurt, everything was inflamed. Like the nose, mouth, vaginal area, everywhere. And I also got hemorrhoids right away, within three weeks, and that was brutal pain, I didn‘t know how to deal with it. The onset of side effects was usually unpredictable. Several might occur suddenly and without warning, or they might develop gradually; so it was impossible to know what condition one would be in even two hours in the future. One man  said that “in addition to the work, it was quite hard, since there was no central thread and one couldn’t say how one would feel; there was no rhythm”.The symptoms led to decisive changes in the patients’ lives, against which they struggled. Their daily lives changed totally.The patients reported that, since starting therapy, nothing was the same as before. Mind and body, and emotional life no longer functioned as usual and considerably reduced the quality of life. One man described the effect as follows:Absolutely nothing is the same as it was, neither sleeping nor feeling, simply mind or body, it’s not the same any more, no; even when I touch myself, the whole feeling is simply different; smelling oneself changed; there’s a disgusting taste in the mouth and food tastes different. Nothing, really nothing is the same anymore.  said she “could no longer lead a normal life and only slept after work”. In addition, for example, one was “no longer able to open a bottle, concentrate for any length of time at work, or stand the lively children and not react with hostility”. What strength remained was often focused on existential priorities such as one's employment or essential everyday tasks; others were pushed back. A man reported:One serious problem for the patients was their lack of productivity, which was usually attributed to great fatigue and accompanied by an absolute lack of energy and strength. They were unable to satisfactorily perform everyday tasks at home, at work, as partners or as parents, which could result in further difficulties. One woman And as for my wife, she doesn’t get what she would like. I can’t give her what I don’t have at the moment. That also has to do with potency, there’s such a loss of strength, loss of desire, it’s really terrible for our relationship because I have no strength. And sexuality is one area in which strength plays an important role, and if it’s not there, there’s frustration. Prior to therapy, most participants' HCV infections had produced no readily apparent symptoms. Considering their therapy a very personal matter, they discussed it with few others, and hoped to prevent the side effects from becoming obvious. However, these were virtually impossible to conceal, and many were ashamed of their condition and appearance. To protect themselves and their families from gossip and isolation, most carefully selected to whom and how fully they revealed the details of their HCV infection. Otherwise, they developed strategies to avoid disclosure. For example, many withdrew from their social environments during the therapy period, leading some to feel very isolated. One man described this as follows:I hid it for one reason because I really didn’t know how people would react. In my environment, it’s a touchy subject and people are talking about who has the disease and why. Another main reason is my ego, I don’t want somebody to judge me as sick. It would be enough to see just one glance from someone that tells me, you think I’m sick. If I’m sick, then I’m sick, I’m absolutely not ashamed of it, but it is doubtlessly a peculiar situation, in which [as long as] I don’t admit that there’s something wrong, there’s nothing wrong. Moreover, if anyone points at me and says "sick", it would be awful. There are, of course, people I could tell this to, surely, but in the background I always think some day he will tell it to another person, that’s why I just keep my mouth closed; I simply didn’t want anyone to know. The changes which were experienced as decisive were often hard for the patients to bear and they needed a lot of strength and willpower to battle on. This also brought them to the limits of their resilience.Initially the patients were confident that they could complete their therapy regardless of the difficulty. However, the changes they recalled as most decisive pushed them to the limits of their strength, willpower and resilience. Struggling with symptoms, they described losing their feeling of self, which left them unable to assess themselves appropriately. This sometimes led to dangerous situations, in which they felt very dizzy or even collapsed. Some recalled how limited their judgments and actions became, or how they feared losing control because of depression or aggression. One man explained:There were situations in which I felt so awful that I almost wanted nothing so much as to be admitted to hospital,…at the end of my rope, emotionally and physically. I know when I’m sick, that usually it will pass, and I don’t see the doctor. But this time the limit was overstepped where I am no longer able to judge, and that was a certain danger, since I live alone. There were situations in which…I would have best liked to be in hospital [outpatient clinic] that I was judged by someone else. Most patients regarded their HCV healthcare providers as valuable sources of support regarding unpredictable symptoms. Offering short-notice appointments via telephone, text message or email, these low-profile, reliably accessible clinicians were extremely helpful to evaluate symptoms or problems with treatment regimens. Concerning symptom control, though, while patients understood that the newness of the protease-inhibitor-based triple therapy made full management impossible, they were surprised at how limited the clinicians' knowledge was. Nevertheless, they appreciated clinicians who empathized with them and assisted in any way in their battle against side effects. This gave them a feeling of support and partnership in seeing their therapy through:I had the feeling that even for my nurse and doc this was not routine. Then I realized they were fighting along with me. I really absolutely knew: I suffer from something they don’t really know about. But let’s say, at the worst point, both of them stood with me. Patients expected healthcare providers to accurately evaluate their health status and take the lead when they themselves were too impaired to assess or react appropriately to a crisis. One woman  recalled being unaware that she was approaching the point of collapse, and emphasized that, though she understood her clinicians' lack of specific experience, it would have been helpful if one had intervened and sent her to hospital earlier.Many participants recounted how their inability to describe their symptoms had sometimes prevented them from informing their care teams either promptly or clearly. Also, due to their high number of symptoms, they usually mentioned only those that caused the most stress. Further, they were unaccustomed to reporting symptoms emphatically enough for them to be noted. In retrospect, patients rated open communication with clinicians, including discussions of even the slightest change during therapy, as essential. One noted that the care personnel could not be expected to be “clairvoyant”.Patients had tremendous faith in their clinicians' advice. Despite information about side effects, and even in difficult situations, many followed therapy instructions precisely and without question. One man reported:I simply took the medication without question and thought, you’ve got to take this every eight hours; but I didn’t think anything bad, I simply took it without question. The doctor said I must take it this way. At the end it was difficult, but I didn’t know who was to blame, then, when I suddenly had attacks of shivering. I never would have thought it was because of the medication, someone should have told me more clearly.  said “I would have missed all my appointments because of drowsiness if my father hadn’t helped me with the appointments and driven me there”.Beyond their clinical care, several patients explained that, considering their often very poor physical and emotional condition, they genuinely needed and received extensive support in everyday tasks, and said support from partners, family and friends helped them endure the therapy. These people helped with such tasks as housework or organizing and keeping appointments, and even occasionally supplied motivational talks or instructions for action. This level of assistance usually entailed a great challenge for the supporting person, and required close cooperation with health care providers. Conversely, living alone without support during the therapy period was unanimously rated as problematic. One man The majority of patients found medication management difficult and time-consuming. However, even though their regimens required injections, timely intake of medications three times a day and food restrictions, none mentioned this explicitly until asked. Once the topic had been introduced, though, all acknowledged the importance of taking medications exactly on time. They also described phases during which taking medication was easier and others when they had to force themselves to overcome feelings of aversion. Nonetheless, despite the difficulties, to maximize their chances of attaining a cure, they summoned the necessary discipline, and eventually taking medication became routine. Of the entire participant group, only two men, both formerly IDUs from substance abuse treatment clinics, reported that they couldn’t take the medication three times daily as prescribed by the doctor because they were too drowsy and couldn’t wake up on time. Their IFN injections were administered to them weekly by a nurse, which both rated positively. One was able to reduce his medication intake to twice daily after consultation with his health care providers, enabling regular administration from then on. The other terminated PI intake due to unbearable side effects and continued with dual therapy.In summary, all patients considered the triple therapy an enormous physical and emotional battle: perseverance demanded all of their willpower and discipline. Their motivation was the possibility of cure and adherence with their medication regimen was not a foremost topic, in spite of the radical changes and burdens brought on by the many side effects. These were often unexpected and difficult to discuss or manage. As a result, patients operated at the very limits of their endurance, and all collaboration between HCPs and patients was exploratory, i.e., as PI therapy was extremely new, the clinicians' experience was severely limited and related literature remained scant. Still, regardless of their potential therapeutic success, all of the patients were confident of the value of their decision to undergo therapy.This thematic analysis provides insights into HCV patients' experiences with PI based triple therapy. Before beginning their therapy, these patients were powerfully motivated to improve their health and achieve a cure. For dual therapy, patients have associated concerns regarding disease progression, loss of liver function and other potential health problems with treatment initiation , 44. HowSoon after starting triple therapy, our highly-motivated study group found themselves struggling. The constitutive theme–“Fighting an uphill battle”–describes the patients' common existential experience of coping with the therapy's side effects and indirect negative consequences. Bell et al. describe similar existential treatment experiences among cancer patients receiving adjuvant chemotherapy . HoweverIn this study, despite information from healthcare providers and research oriented treatment reports, the symptoms experienced surpassed the patients' expectations (as described in the “Encountering surprises” subtheme). Across chronic conditions, high symptom numbers, high symptom distress and low perceived symptom manageability have negative impacts on health outcomes including quality of life and medication adherence , 49. GivAs described above in the subtheme “Reaching the limits of systems” the therapy's drastic physical and emotional effects fundamentally disrupted participants’ everyday lives and severely limited their social interactions. Similar phenomena have been described for symptomatic but untreated HCV patients, as well as for other chronic conditions .However, the radical social changes described by our study participants appeared heavily influenced by their fear of stigmatization. In order to protect themselves from negative social consequences, it is common for patients with stigmatized infectious diseases such as HIV and HCV to make careful disclosure decisions and in some cases conceal their conditions as fully as possible –54. Our The importance of social support is also apparent in the “Reaching the limits of systems” subtheme. Participants recalled both how their symptoms sometimes impaired their judgment and how, during these periods of diminished capacity, the support of family members and close friends was crucial. The positive effects of social support on chronically ill patients' health outcomes is well documented. For example, for patients living with HIV and receiving antiretroviral treatment, a stable partnership is associated with a slower progression to AIDS or death ; and amoSince study patients revealed problems with judgment and efficacy concerning sometimes life threatening symptoms, a sound knowledge of HCV treatment and decision making skills is important not only for patients but for their close support persons. This requires healthcare providers to identify close support persons and integrate them into patient education programs. Where social contact with support persons is limited, professional support, e.g., community care, should be intensified.Based on current evidence and clinical expertise, difficulties in adherence with the complex triple therapy regimens are to be expected , 28, 59.The insights provided by this study illustrate the need to assess patient perspectives of new treatment options in ‘real-life’ settings–as opposed to those of clinical trials. In clinical care, clinicians routinely treat patients who would have been excluded from clinical trials due to medical, social or behavioral problems. Research shows that exactly such medical or socio-behavioral challenges impair results in patients with HCV , 60, 61.The study was limited in two ways: a) its selective recruitment and b) its single-point-in-time interviews. Recruitment was influenced by the fact that participants would be among the first in Switzerland to be treated with the then-newly available protease inhibitors and were therefore both unusually motivated and closely monitored. Single-point-in-time interviews might not have shown individual processes in the treatment experience as well as serial interviews over the course of treatment. However, while the study's qualitative design may limited the results' applicability to other groups of HCV patients, it allowed deep insights into topics such as the participants' inability to describe their symptoms, which could not have been investigated using quantitative assessments.For patients undergoing HCV triple therapy, the burden is extreme, but can be lightened by early and continuous support with the negative effects of social stigma and self-stigmatization. During treatment, social support can be strengthened by the integration of close support persons into patient education. An important goal of this process is to build and strengthen collaborative relationships between patients, support persons, and healthcare providers concerning clinical decision-making. In this respect, wherever possible, health providers should eliminate access barriers and use patient-centered communication styles to assess and support symptom management and medication adherence. With the introduction of DAAs to ‘real-life’ settings, high accessibility and patient-centered symptom and adherence assessment will demand multidisciplinary team approaches that integrate input from both the patients and their close support persons , 55, 56.Additional file 1: Table S1: The six phases of thematic analysis by Braun and Clarke . (PDF 10Additional file 2: Table S2: 15 Item Checklist by Braun and Clarke . (PDF 12Authors’ original file for figure 1Below are the links to the authors’ original submitted files for images.


Scores of toxicological field experiments, which bee scientists and regulators in the United States have looked to for definitive causal evidence, indicate a lack of support. This paper analyzes the methodological norms that shape the design and interpretation of field toxicological studies. I argue that contemporary field studies of honey bees and pesticides are underpinned by a “control-oriented” approach, which precludes a serious investigation of the indirect and multifactorial ways in which pesticides could drive declines in honey bee health. I trace the historical rise to prominence of this approach in honey bee toxicology to the development of entomology as a science of insecticide development in the United States. Drawing on “complexity-oriented” knowledge practices in ecology, epidemiology, beekeeping and sociology, I suggest an alternative socio-ecological systems approach, which would entail  The viability of multiple agricultural crops and broader ecosystems is threatened by unsustainable declines in the populations of honey bees and other insect pollinators in North America and elsewhere ,2,3. SinIn-situ beekeeper-initiated field studies suggest that CCD is primarily due to the progressive and interactive effects on developing bees of chronic exposure to “sub-lethal” levels of these insecticides, which are brought back to the hive by bees foraging on contaminated pollen and nectar cute toxicity tests on adult honey bees may be particularly ill-suited for the testing of systemic pesticides because of the different route of exposure bees are likely to experience in field applications. Chronic feeding tests using whole colonies may provide a better way to quantify the effects of systemics” ts much easier to test for”. And as a result, Pettis believes that scientists “tend to ignore interaction” (: p. 228)et al.  are conset al. ,26, theiagricultural research in the U.S. Early entomologists at land grant universities, state agricultural experimental stations, and at the USDA attempted to enhance their professional positions by convincing growers and others that extant problems in agriculture were mainly due to insect pests, and that they possessed the appropriate knowhow to provide the solutions [Through analyses of semi-structured interviews with relevant stakeholders, published documents, and ethnographic research at a bee biology laboratory that is examining the links between agrochemicals and CCD, my prior research has illuminated how a particular set of “control-oriented” research norms and practices from agricultural entomology came to dominate scientific investigations of the links between pesticides and honey bees, and in the process marginalize the knowledge claims and positions of several beekeepers in the CCD controversy over the newer systemic insecticides . The priolutions ,38,39. Solutions ,41,42, r50—the dose of a chemical at which 50 percent of the exposed group of bees is killed within a period of 2–3 days—and used it to rank the relative lethal toxicity of “organic insecticides” such as gamma benzene hexachloride and DDT to honey bees [Journal of Economic Entomology [Early bee scientists doused “non-target” bees in laboratory and field settings with pre-determined amounts of individual chemicals and measured various indices of mortality relative to “control” (untreated) bees . In the ney bees . In the ney bees . Followiney bees ,42. Bee ney bees , and to sub-lethal effects of pesticides in interaction with shifts in other ambient factors such as fragmentation of the landscape, nutritional availability, quality and diversity, pathogens, and exposure to other synthetic chemicals occurring over multiple generations of a bee hive’s lifecycle were not given equivalent consideration by these scientists. Thus, based predominantly on such a “control-oriented’ approach, Anderson and Atkins [These investigations of pesticides in relation to “non-target” honey bees by bee scientists were underpinned by the very same “control-oriented” experimental approach that characterized their peer entomologists’ efforts to help develop more effectively killing chemicals against “target” insects. Similar to the latter, bee scientists emphasized the relatively rapid, lethal effects of individual pesticides on honey bee health in their studies. This then meant that d Atkins , who werd Atkins ).research problem that is geared toward the norms of professional success in peer institutions, such as in university departments, scholarly academic journals and grant funding agencies. The high stakes involved in securing publications, grants and tenure, orient academic bee scientists toward adopting historically established control-oriented research norms and practices, because they have a higher likelihood of leading to conclusive and publishable results. Furthermore, whether results from field experiments are “conclusive” is based on a statistical cut-off at a 95% confidence interval; this criterion is a social convention. It glosses over the enormous variability that is present in field settings both between and within honey bee colonies. As a result, experimental field studies tend toward concluding “no differences” between pesticide-treated and untreated honey bee colonies, when in fact there might be a difference. This preference for false negative results (Type II error), where a substance is incorrectly concluded to be safe when in fact it is harmful, is compatible with the livelihood stakes of academic scientists. This is because a false negative would lead a researcher to miss a discovery but not damage his or her reputation to the same degree as a false positive, which might be more professionally damaging when it is revealed to be incorrect and causes the researcher to retract the publication [In the aftermath of widespread public concerns about the negative effects of industrialized chemicals on human health and the environment in the 1960s, regulatory and academic interest in the real world effects of pesticides on “bioindicators” such as honey bees substantially increased. Since then, the prevalent “control-oriented” approach has come to influence and be further shaped by academic bee scientists, for whom the issue is first and foremost a lication .gaps created by the control-oriented character of field research pertaining to pesticides and honey bee health are further maintained by the career structure of academia. Field research about the cumulative effects of the newer systemic insecticides in interaction with other factors remains largely “undone”, in part because it is very hard to measure [shared culture of formal and informal norms, taken-for-granted assumptions, and research practices, which lead these scientists to choose certain research agendas, methods and modes of interpretations. The limits of existing field experiments on pesticides and honey bees point to the need for a revised culture of conceptual frameworks, research norms, and modes of knowledge production that emphasizes a better balance between experimental control and environmental complexity.The  measure ,44. As acontext-sensitive settings”  “onttings” , where it is simply not feasible to ask the kinds of narrow cause-effect questions or to carry out the sorts of replications that a control-oriented approach would entail. This scenario is arguably true for honey bees as well. Each honey bee colony is conceivably a “complex adaptive system”; a “superorganism” , which cwhy some colonies but not others are exposed to certain risk factors, and what other kinds of changes occur that lead to the exposures. In other words, even if honey bee epidemiologists identified certain pesticides to be prominently associated with a particular bee disease, the social circumstances that mediate this exposure remain to be fully integrated as a crucial aspect of the broader analysis. Local human activities, including science, beekeeping, and agricultural policies and practices, play an integral role in honey bee colony health, and this calls for an approach that conceptualizes honey bee health in terms of a socio-ecological systems framework [et al.’s BIP initiative [economic one. There is no doubt that the costs of managing honey bee colonies constitute a significant “bottom-line” concern for commercial beekeepers. But that bottom-line is in itself a consequence of social factors, such as government policies and yield-oriented institutional logics and practices, which led to huge increases since World War II in monocropping operations, pesticide and fertilizer usages, and accompanying die-offs of endemic pollinators [Moreover, while it is essential to ask what “risk factors” diseased and healthy colonies are exposed to, this is not at all sufficient. Complexity-oriented field research on honey bee health would prompt scientists to ask ramework . While vitiative  recognizlinators ,53,54.et al. [The socio-ecological systems framework emerged during the last decades of the 20th-century amidst an increasing realization that ecological research must incorporate human impacts, and conversely, sociological research must incorporate ecological effects. Through a series of case studies, Liu et al.  outlinedet al. , p. 1513A socio-ecological systems approach to field studies of honey bee health would seek to shed light on how multiple factors across social, historical and ecological contexts interact to influence ongoing patterns of honey bee health. It would involve humanistic researchers versed in analyzing the complicated interplay between cultural norms, governmental policies, and fact and artifacts in scientific and non-scientific fields ,44,47,48The design and implementation of a viable socio-ecological system approach to field studies of pesticides and honey bee health would also need to involve beekeepers and their field knowledge in a meaningful and egalitarian manner. Informal beekeeping practices of gauging hive health and disease constitute a highly valuable source of “local” knowledge about the dynamic and multidimensional aspects of honey bee colonies. For example, beekeepers assess brood health by identifying the overall pattern in which various developmental stages of honey bee brood are distributed across a colony’s comb. The “brood pattern” additionally provides information about the queen’s health, local nutritional resources, and the presence of diseases. Informal measures, such as brood pattern, produce knowledge that is unquestionably practical, which means that commercial beekeepers will seriously consider the influence of multiple environmental factors, not just those that are easily isolatable and definitive from the standpoint of control-oriented scientific practices. Of course, commercial beekeepers’ approach to understanding the factors that affect bee health is shaped by their stakes in keeping colonies healthy and alive. It engenders knowledge that errs on the side of arriving at false positive conclusions (Type I error), a precautionary approach where a substance that is safe might be incorrectly labeled as harmful.While it is all well and good to call for greater beekeeper-scientist collaborations in the design, implementation and interpretation of field studies, the reality is that in the eyes of many academic, regulatory and agro-industry scientists, beekeepers’ knowledge of bee health is “anecdotal”, “simply trial and error”, and “not data” . So, simtransdisciplinary set of “theoretical structures, research methods and modes of practice” [In other words, what I am calling for is the development of a ractice”  that extHow might such transdisciplinary collaborative research take shape around examining the purported links between newer systemic insecticides and honey bee health? At the outset, it would entail a series of structured deliberations over the course of two years between key stakeholders. Deliberants with diverse methodological and conceptual tools for place-based analyses, high levels of credibility among professional colleagues, a history of productive relationships, and an openness to non-traditional approaches, would be recruited from an array of relevant stakeholder groups—beekeepers, growers, university scientists , university sociologists, extension agents, and public officials. Facilitated deliberations between participants would be interlaced with a pilot field study on honey bees, which would be designed, implemented and refined based on the ongoing deliberations. Subject to revision by the deliberants, the pilot field trial would span two successive summers, and would compare the relative health of honey bee colonies across four field-sites: monocropped fields and polycropped fields managed with or without “reduced risk” systemic insecticides. Deliberants would learn about each other’s knowledge and practices, discuss the design features and measures, and engage with broader stakeholder communities, in order to arrive at an agreed upon experimental design, which would subsequently get implemented.practical information. Findings would also address current gaps in the scientific realms regarding the mechanisms that mediate the interactive effects and buffering capacities of honey bee colonies.The main aim of this paper is to prompt bee scientists to consider revising the existing norms and practices of experimental field research regarding pesticides and honey bees so as to better incorporate the social and ecological complexity in which honey bees and beekeepers operate. The worlds of scientist and beekeeper research about large-scale declines in honey bee populations, including CCD, have been largely separate, with beekeepers’ field knowledge pointing to a prominent role for a new set of insecticides, and toxicological field experiments pointing to a lack of conclusive evidence supporting beekeepers’ claims. Based on my ethnographic and socio-historical research ,44, I ar


In the available psychological literature, affect regulation is fundamentally considered in terms of self-regulation, and according to this standard picture, the contribution of other people in our affect regulation has been viewed in terms of socially assisted self-regulation. The present article challenges this standard picture. By focusing on affect regulation as it unfolds in early infancy, it will be argued that instead of being something original and fundamental, self-regulation developmentally emerges from the basis of a further type of affect regulation. While infants’ capacities in recognizing, understanding, and modifying their own affective states are initially immature and undeveloped, affect regulation is initially managed by the other: it is initially the self, and not the other, that plays the role of an assistant in affect regulation. To capture this phenomenon, the concepts of “auto-matic,” “hetero-matic,” and “altero-matic” affect regulation will be introduced and their interrelations elaborated. By showing how the capacity of affective self-regulation, which is characteristic to maturity, is developmentally achieved by internalizing regulative functions that, at the outset of development, are managed by the caregiver, it will be argued that altero-matic affect regulation is an autonomous type of affect regulation and the developmental basis for self-regulation. Affect regulation refers to the mechanism by which our emotions, moods, feelings, and their expressions are modulated in pursuit of an affective equilibrium or homeostasis. Its central relevance for the functioning of the human mind is being increasingly acknowledged in current scientific research and the topic has been approached from various perspectives. In the ongoing debate, the focal research interests and questions lie in the biological and evolutionary bases of affect regulation, in its cognitive underpinnings, in its development, in the correlation between regulative capacities and various personality features, and in various disorders of affect regulation as well as in their treatment. Characteristically, affect regulation is understood as “the process of initiating, maintaining, modulating, or changing the occurrence, intensity, or duration of internal feeling states and emotion-related physiological processes (…) often achieved through effortful management of attention (…) and cognitions that affect the interpretation of situations (…) as well as through neurophysiological processes”  are considered, they are interpreted in terms of mediators or facilitators of self-regulation. That is to say, even if authors are today increasingly acknowledging the need to integrate a social perspective more intimately into the theory of affect regulation  by something within oneself (Gr. auto-). To be sure, even “auto-matic” affect self-regulation may be passive or active , or by taking painkillers, thereby medically erasing the nascent pain from within.In the present article, I will be challenging this standard picture. Even if self-regulation undoubtedly has a relatively large role in the affect regulation – at least in adult life where we are held responsible for controlling our affective impulses and behavior – it might still be that not all affect regulation is in this sense literally “auto-matic,” i.e., set into motion or animated  to experience (particular kind of) social attention, we decorate our apartment to feel at home, we put on our favorite music to get into a particular mood before going to a party, and we switch the TV channel whenever the program feels uncomfortable for one reason or another. Despite the obvious motivational differences among these cases, all of them seem to share a common structure: they are all about active manipulation of one’s immediate experiential environment in pursuing to modify one’s affective stance. In contrast to what I called “auto-matic affect regulation” – where regulation is managed by something within oneself – I will call this “hetero-matic affect regulation,” since here the regulating source lies outside the boundaries of oneself . Hetero-matic regulation accordingly amounts to regulation of the self by something that is not the self.However, while trying to deal with an unpleasant feeling, besides modifying ourselves, we may also modify our environment. That is to say, the self may not only adjust to the prevalent external circumstances but also actively modify the latter to better match with one’s current affective moods and needs. For instance, feeling the nascent headache, we may dim the bright lights, put on some peaceful music, and so on, thus engaging in what has been called environmental “niche construction.” The term derives from the field of biology and refers to the manner in which organisms may actively transform their environment to make it fit with their needs – beavers building dams to enable an optimal ecosystem has been used as the paradigmatic example of such niche construction . Just asother-based, and I will call it “altero-matic affect regulation” .2 What I have in mind here is the following. Besides the aesthetic appearance of others  we are also affected by their subjectivity , and we tend to be particularly sensitive when their experiences are directed at us. In everyday adult life, others function as “social mirrors” for us, and we tend to be rather sensitive in respect to what we see in the mirror  are not secured all the time – and not even most of the time. The mentioned “slide” is as justified as the claim that since human beings have the faculty of reason – after all, we are animal rationale – human life is all the time guided by reason. (We are not that reasonable.) Likewise, the fact that there are moments of “alert inactivity,” during which the various remarkable cognitive capacities of infants are actualized, is not a sufficient ground for assuming that the latter are operational all the time. Neutral curiosity is one, but not the dominant, original, or fundamental experiential mode of the infant3.The current research paradigm in developmental psychology builds largely on data that has been gained when infants are observed and examined during moments of so-called “alert inactivity”: the relatively brief periods when they are at their most cognitive, as it were. The concept of alert inactivity was originally coined by affect regulation is required are, by rule, situations in which the infant is not in the state of “alert inactivity.” When the infant is haunted by pressing needs, in plight, feeling uncomfortable, or sedated by overwhelming satisfactions, neutral curiosity remains impossible – not just difficult as in adult life – and the infant’s world is rather organized in the light of her felt needs and satisfactions. The distinctions fleetingly established, and documented, during cognitively oriented moments are not initially so deep rooted that they would, during the first weeks, go on to organize the infant’s experiential reality also during periods when the infant is hungry, for instance. In the baby, the sense of hunger is not present as a subjective topping to the objectively organized world. As Winnicott puts it, “being hungry is like being possessed by wolves” , “dyadic regulation” (see section “Dyadic Regulation: The Mirroring Other as a Beacon of Orientation”), and “increasing self-regulation” . These three levels, which surely also overlap, match with the threefold developmental division by Donald Winnicott, between “absolute dependency,” “relative dependency,” and autonomy or “independency” (During periods when affect regulation is required differentiation between self and (m)other is all but clear, and it comes in degrees.endency” , p. 46.how she herself feels and how the other feels. To exemplify this, consider the phenomenon of emotional contagion. In a standard setting, when one baby in the room begins to cry, the other baby in the same room tends to follow suit. It would not be convincing to maintain that the second baby is just “empathizing” or “sympathizing” with the first baby, while maintaining a clear interpersonal distance. Unlike empathy and sympathy, emotional contagion is “self-centered” . Rather than mistaking someone else’s sadness as her own, the infant senses an emotional presence and sucks in like a sponge. The feeling that the second baby is infected by is accordingly not felt by her as someone else’s feeling, but as her own  protective hands vs. the disturbing noise (of the ambulance), – the former might not yet be clearly differentiated from the infant herself. In other words, for the infant, affect regulation is not experienced as altero-matic, other-initiated. Just consider the case of emotional contagion: what the infected baby is preoccupied with is the feeling, not the source of the feeling. During times of need, the caregiver plays the function of a regulative shield, and she might not be experienced as being anything more than that  may even be disturbing or irritating, aversive rather than inviting, and slightly different but affectively matching works the best.A further factor promoting self/other differentiation relates to the fact that the caregiver’s affective presence is increasingly divided into such expressions that clearly eraction . Gergely9 The infant reportedly tends to disengage when the caregiver no longer markedly mirrors the infant’s affects. This happens when the caregiver’s attention turns elsewhere – in the midst of interaction she may exchange a few words with her spouse, become lost in her thoughts, or start rambling with her smartphone. The break is decisive: as long as engagement is held up, the infant’s affective shifts and modes are echoed or mirrored in what she externally perceives – being surprised or delighted, for instance, is given immediate “feedback” in the form of a change in the affective presence of the caregiver. Once engagement is interrupted, how one feels no longer seems to have any effect in the environment. For the time being, contingency is gone; the caregiver’s face is no longer altered by the infant’s natural “invitations,” and she is thus prone to disengage: “If the mother’s face is unresponsive, then a mirror is a thing to be looked at but not to be looked into”  becomes sad herself and starts to cry, (ii) whether in the other’s body language you clearly see that she realizes how sad you are , (iii) whether she faces you with a neutral and unresponsive expression , or (iv) whether she does not seem to notice you at all. The first case is a matter of emotional contagion: you find the other being infected by your emotion and becoming sad herself. It is then her own sadness that she bodily expresses. By contrast, in the second case your own sadness is affectively mirrored back to you: unlike in the first case, what the other’s expression is here taken to convey is not the other’s feeling but your own: you find your own sadness receiving expression in the other’s body. In the third case, you may find your overt emotional state being considered from afar, perhaps evaluated or contemplated, but not mirrored back to you in the affective register; the others expression is not affected by your overt sadness: by maintaining a neutral expression, the other also maintains an interpersonal distance as if telling you, “I can see that you are sad.” In the last case, again, your emotion in not recognized at all: it is as if you were invisible to the other.Via repetition, the infant begins to catch the qualitative difference between mirroring, attuned, and engaged affective data, on the one hand, and non-attuned or non-engaged affective data, on the other. The prominent distinguishing feature lies in what Gergely and Watson call “contingency detection”  reflection, but rather that by looking at the mirroring other, the baby is already executing a kind of reflection: in engaged interaction with the mirroring other, she is gradually being taught how she herself feels.10 Such “teaching” assumes the form of what Gergely and Watson call “grouping”: various affective contours that the infant goes through in a non-articulated and pre-symbolic manner are, via consistent repetition, brought together in the expressive “feedback” of the mirroring caregiver. To simplify, the infant’s unpleasant affects , which are all expressed by crying, are increasingly grouped by the mirroring caregiver. As Bowlby puts it, “the ordinary sensitive mother is quickly attuned to her infant’s natural rhythms and, by attending to the details of his behavior, discovers what suits him and behaves accordingly”  givenness.The capacity to dissect one’s affective life into clearly outlined categorical states is a later developmental achievement. Even if infants seem to naturally distinguish pleasurable affects from unpleasant ones, they hardly divide their affects into two clearly separate categories – and it would be even less convincing to claim that they initially categorize their unpleasant affective modes into states of “anger,” “hunger,” “pain,” “tiredness,” or “fear,” for instance. Before the infant learns to articulate and track  her affective life in terms of specific affective “states,” her affective life already runs its course in the form of pre-reflective affective contours and tones – a phenomenon captured by the concept of “vitality affects.” The latter amount to the dynamic patterns of affective experiencing on the whole  the infant’s exposure to other affective sources in the environment. As the dyad is increasingly formed and stabilized along with the differentiation between the caregiver and the environment, the infant begins to differentiate between expressions that reflect the caregiver’s own affective states, on the one hand, and marked expressions that mirror her own affective modes. This differentiation enables the infant to recognize, with increasing precision, her occurring feelings – to monitor them, to reflect upon their relationship with other affects, and hence to categorize and distinguish between them. This marks a decisive step in the development of the ability of self-regulation.The caregiver’s contribution to affect regulation at the outset of development can hardly be overestimated. At the outset, the caregiver largely way in which her affects are mirrored. The infant gradually learns to differentiate between two modes of mirroring: those signaling situational approval and those signaling situational disapproval. Along with increasing differentiation in this respect, the parent gains a normative significance: the caregiver’s face indicates not just how one feels, but also whether how one should presently feel . In other words, the caregiver is a “beacon of orientation” not just in the descriptive but also in the normative sense: besides consulting the caregiver while seeking an answer to the question, “How do I feel?,” the infant now increasingly seeks an answer to the question, “How should I feel?”A further mirroring function of the caregiver is still to be discussed. As the infant becomes more skilled in distinguishing the caregiver’s mirroring expressions from expressions that reflect the caregiver’s own feelings, she also becomes increasingly sensitive to the suggestive. Consider the case in which a 9-month-old baby is about to take a step without support, and just before doing so turns to consult the caregiver’s facial expression. In the words of Gergely and Watson, the infant might be “actively seeking out a clarifying affect-mirroring cue from the parent that will result in the strengthening and coming to dominance of one of the conflicting emotion-states he/she is currently in, thereby resolving his/her indecision” (ibid.). The infant clearly wants to take a non-supported step but feels afraid in the face of the uncertain outcome, and to resolve her affective indecision, she consults the parent’s face – not in order to know how she herself already feels (or to know how the caregiver feels), but to know how she herself should feel. If the adult looks uncertain and afraid, the infant tends to give up the idea, and if the parent is overtly supporting, smiling and “giving a green light,” the infant will more easily try taking an unsupported step. What the parent’s expression here regulates is the infant’s affective stance . Likewise, whenever the infant harmlessly falls and bumps herself to the floor after a failed first try, she is prone to consult the parent – and, again, if the latter stays calm (perhaps making a markedly funny face and saying “whoops!”) the child also will much more likely feel calm about what happened and reacts less dramatically than when the parent is overtly terrified and concerned. Besides future-oriented suggestions, social referencing is also used to evaluate something that has already taken place; instead of consulting the caregiver, asking, “Is this OK?,” the infant also consults the caregiver, asking, “Was this OK?” Consider that at a dinner table a toddler deliberately pours a full glass of milk onto the table, cheerfully smiles and titters, and then carefully turns toward the caregiver . The affective impact upon the child is different depending on whether the caregiver just smiles and laughs along, thus signaling approval, or whether she recognizes the infant’s cheerfulness, but holds a more serious look, thus signaling that deliberately messing up with food is not a laughing matter.This issue has been discussed under the rubric of “social referencing” e.g., . Social internalized. Consider an infant who is learning to walk, and who, each day, falls dozens of times. Consider that the infant does not hurt herself that badly, and that her caregiver greets her efforts with soothing encouragement . After a while, when the infant falls, she already knows to expect such soothing encouragement, and her affective reaction to falling down is, in this sense, less dependent upon actual parental consultation – she no longer each time seeks the gaze of the parent and, at some point, does not any longer require the caregiver’s actual presence to feel the soothing encouragement: “It’s ok, just try again.” Negative situational mirroring patterns become likewise internalized. Consider the milk-pouring example: by being consistently mirrored with a negative tone each time she deliberately pours her milk glass, the child gradually internalizes the situation-dependent blame, and is able to anticipate the unpleasant outcome. In this manner the child becomes learned in what could be called preventive affect regulation: avoiding situations usually leading to unpleasant other-based affects (such as blame or shame).Now, along with the increasing capacity to track how she feels, the infant begins to anticipate dyadic mirroring of her affective experiences: parental mirroring is gradually self-regulation: the child increasingly follows social expectations also in the absence of external monitors, and she leans on the internalized presence of the altero-matic regulator also when the latter (the caregiver) is not actually present , whereas on the other hand she does not refute the caregiver’s existence either . For an analogical experience in adult life, just consider watching a thriller movie: when you are absorbed in the film, you might feel afraid when in the film a murderer suddenly jumps from the closet, but when that happens you do not normally call the police ; on the other hand, if you treat the thriller as a being only a movie, and judge the murderer not actually being there, you would not be afraid and could not enjoy the movie. Likewise, the infant playfully, spontaneously, re-enacts the caregiver’s presence, without making existential judgments one way or the other, as it were – questions of actuality remain undecided  caregiver; her question is rather more social and general: “How am I expected to feel by these-and-these others, and how do I myself feel?”Insofar as the infant carries the primary caregiver within her, she is increasingly capable of affect regulation also outside the infant–caregiver dyad. Gradual internalization thus slowly facilitates the infant’s process of separation from the primary caregiver, thus preparing a way toward independence  with respect to affect regulation. Gradually differentiating herself from the primary caregiver enables further dyadic relationships: other people, too, are constituted as social mirrors, and different people reflect the child’s affective states differently. Increasingly differentiating between these alternative self-evaluations, she also begins to favor some over others. For example, knowing that her mom is stricter about cookies, the child tends to ask her dad whether she could have one more – her dad is expected to mirror her desire in a more approving lighting. More generally, as the child gains more reflective surfaces to her feelings and impulses, alternative perspectives to the appropriateness and inappropriateness of her affective expressions, her social self-awareness and situational prudence become gradually structured. By entering the social world, the child no longer sui generis form of regulation. The basic reason why altero-matic regulation cannot be reduced to assisted self-regulation is that in early infancy the child’s subjective regulative capacities are remarkably insufficient. To think that all that the parent does is to support the infant’s self-regulation is as reasonable as saying that a parent “supports” a teenager in cleaning her own room by cleaning it herself. Infants are born helpless: they enter the world in a state of absolute dependency  resist our attempts of manipulation and (2) regulate our affects without any intentional activity on our part. The first phenomenon is familiar from our everyday social life, where the gap between our own affective life and the affective life of others is relative clear: we might ask the other to do something, but the outcome is, in principle, unsure. By contrast, a stereo equipment does not have plans of its own; when we want to hear our favorite song, we can just put it on. The second phenomenon is likewise characteristic to everyday social life, though more emphatic in infantile experience. The stereo equipment does not track our emotional states, and function accordingly without any intentional activity on our part, but the other person might see that we are sad, for instance, invite us to talk about it, or put on our favorite song, thus in various ways “mirroring” our feelings without asking for our permission. That is to say, without any active effort on our part, others may regulate our affects, and they may do this either directly or by modifying our environment. In certain circumstances, however, significant other persons may themselves be present as figures within the environment. In a favorable developmental setting, care can be taken for granted  may see me stealing something, for instance, even if I am sure they presently do not, may give rise to enormous guilt. In fact, some people that are (presently or permanently) absent may even have a stronger influence on the organization of our affective life than those that are actually present at the moment.One further distinguishing feature is worth highlighting as it supports the claim of the a mirror, to rephrase Winnicott, but also the “precursor” of the mirror, and the way that one is mirrored in early childhood largely colors the way one expects oneself to be viewed later on  avoidant, (3) resistant or ambivalent, and (4) disorganized or disoriented attachment  caregiver is not just later on , p. 149.secure attachment , the caregiver is attuned to the infant’s affective life. Holding attachment in value, the caregiver is emotionally available, perceptive and responsive to his or her infant. In such a setting, the infant is consistently perceived, understood, and responded to by the caregiver  situation in which one spontaneously expresses one’s feelings but is not seen (or worse: is humiliated), the child tends to become rather cautious in respect to what she externally reveals, and this complementary deliberation may assume the form of what Winnicott calls a narcissistic false self organization  auto-matic regulation, but to (an indirect form of) altero-matic regulation. Given the complexity of everyday social life, all these forms, along with their indirect variants, have a share in our affective life, and it may be hard to distinguish them from one another. Yet, given the developmental primacy of altero-matic regulation, and the fact that auto-matic regulation is largely derived from the latter, we can maintain that altero-matic regulation is an original phenomenon.altero-matic affect regulation. Venturing through pre-dyadic and dyadic forms of early affect regulation, I showed how self-regulation becomes increasingly independent as the developing child gradually internalizes the regulative functions that are initially managed by the caregiver. In this manner, self-regulation is gradually established from the basis of altero-matic affect regulation, and altero-matic regulation therefore cannot be reduced to assisted self-regulation. Self-regulation becomes possible thanks to a particular kind of altero-matic affect regulation, which makes it understandable that if something goes wrong in the latter, the traces of this are to be found, even if only later on, in the former.I have here suggested that the standard picture, according to which affect regulation is interpreted in terms of (assisted) self-regulation is misleading, because the latter is developmentally based on another type of regulation: the manner in which we are capable of regulating our affects – whether directly or by modifying the environment – largely depends on the developmental course of what I have called The author confirms being the sole contributor of this work and approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Pisum sativum, garden peas. The monastery with its beautiful Gothic church  in 1858/9 and who taught in it, as did Mendel Fig. Februaryurch Fig. was locaOberrealschule, the monks and their secular fellow members and guests of the Society of Natural Sciences (Naturforschender Verein) left their top hats, canes, and capes in the lobby, took their seats close to the stove, noting the officers of the Association moving forward to where Mendel had seated himself in the front row. The Vice President of the Association, the distinguished botanist Carl (or Karl) Theimer, announced the evening's agenda and asked the Association's equally accomplished secretary, the botanist and astronomer Gustav V. Niessl to introduce the speaker, Mendel, and invited him to give the first of his two presentations on Experiments in Plant Hybridization (Versuche über Pflanzenhybriden). The second, Mendel's summary and conclusion, was given 1 month later (3/8/1865).Entering the theory of descent with modification through the action of natural selection proposed by Wallace and Darwin.Thus, more or less imaginatively retold, occurred an event, surely equal in importance in the history of Western Biology to the presentation just 7 years earlier by Darwin's friends and colleagues to the Linnean Society of London Slotten  on the tfacts, not theory, on inheritance, discovered not through natural selection but by artificial selection, that is, by means of plant hybridization. When Darwin finally published in On the Origin of Species by Means of Natural Selection, or the Preservation of Favored Races in the Struggle for Life,” the argument  sustained by and meant to persuade principally by the sheer weight of a huge body of facts and data and inferences drawn from them. The issue it addressed, was condensed into a single word: “evolution” urged upon a reluctant Darwin by Herbert Spencer and used only once in 1859 (“evolved”), in the last sentence of The Origin. Darwin, a 19th century morphologist, was rather conscious of its use until recently in an embryological context. Darwin was equally nimble and expert in adducing animal and plant examples in his book; Mendel, also a 19th century morphologist, confined himself to plants in his presentation, although later he performed experimental breeding with bees. For Darwin, artificial selection was a means of hurrying up natural selection in producing the immense variety of domesticated animal and plant forms from one or more than one ancestor. Mendel dealt with both, wild forms collected around Brünn  and forms under cultivation, mostly for practical agronomical (decorative and edible) purposes. Darwin postulated that it took millennia and hundreds of generations for natural selection to lead to a new species, while Mendel studied modification of plant forms from well-established parent stock in only a few generations. Mendel was fully aware of Darwin's work, as witnessed by his many annotations in the 1863 German translation of Darwin's works preserved to this day in the extensive monastery library and by the use of the word Evolution twice in his subsequently published (1866) paper that summarized both talks. Sadly, the converse is not true, despite the fact that Darwin's first cousin, Francis Galton, wrote to him in 1875 and 1876, asking him to grow peas to test Mendel's laws. Galton also recommended that Darwin read W. O. Focke's Pflanzenmischlinge, which was published in In contrast to Darwin, Mendel, quite aware of the theory of evolution, presented genetics and descent biologically compatible and complementary disciplines. That was almost 60 years after “The Origin…” Darwin lacked genetical and mathematical foundations to explain descent with modification; he was (in our opinion) too prolix, occasionally inconsistent, confused, and contradictory, postulating at last (again after Hippocrates) pangenesis and ending up a Lamarckian (someone whom he had damned roundly on previous occasion).The many words used by Darwin in the first edition of his seminal “On the Origin…” ignited as much opposition and confusion as any prior eureka in biology. Bateson, Mendel's staunchest and most verbal protagonist in England, used Mendelism to bludgeon natural selection acting on generationally accrued, infinitesimal changes, championing instead “sports”, mutations of major developmental effect  in Mendel's paper, except that she still confuses  raised to a power (Potenz) n is said to be expanded (entwickelt) to yield a series (Reihe) of terms (Glieder) which can then be called Entwickelungsreihe [sic] 2 = A2 +2Ab + b2). Accordingly, I [Cotterman] have translated this as a ‘series expansion.’”Versuche from the original, our preference will be “polynomial expansion”, exactly. Iris Sandler's confusion is no different from that of William Bateson . With respect to malformation (Missbildung): Meckel said , abnormal in humans, normal in other species. This limitation is now referred to as “developmental constraint.”Near the beginning of the 19th century Goethe (and Burdach in 1800) introduced the term form  and its formation in the hybrids, as practical an approach to botanical study and the exploration of plant development as that of his father, an expert fruit tree horticulturalist, and that of his mother, a professional gardener's daughter who loved ornamental flowers. Thus, Mendel did not have to mention morphology explicitly. His presentation made it abundantly clear that morphology was the epistemological basis of his botanical and later apicultural investigations. In part, this view of nature , as practical horticulturist, investigator of plant morphology, meteorologist, astronomer, member of the Moravian legislature, administrator of the wealthiest and most renowned monastery of Moravia and of the mortgage bank of Moravia, member of some two dozen learned societies and associations, patron of the arts, and benefactor of the poor.Versuche were the only ones available to Mendel for his presentation or manuscript in 1865/6. Mendel was an extremely hard worker and it can be assumed without risk of contradiction that he performed more, perhaps many more experiments than necessary to make his point. As an outstanding teacher, renowned for his didactic skills, he evidently used great care in sorting his material to make as convincing a case as possible. Nowhere in the records from over a half century have we ever come across even a faint hint questioning Mendel's probity or honesty. This is not to be assumed just because he was a priest, but it was known and universally acknowledged by his contemporaries that Mendel was the very essence of integrity, meriting, after all, presidency of a bank.It would be naïve to think that the data in his Nature. The difference is of the essence and it is cultural, not a failure to correctly apply Chi-squared tests, which after all were not developed until after Mendel's death. Mendel's data were presented not to deceive, but to clarify and to teach. Furthermore, his writings, especially to von Nägeli as early as 1866, suggest that he was asking for others to validate his experimental work.Also, we must not make the mistake of applying present day standards of data analysis and presentation to the style and standards of the 1860s; Mendel did not write for the editors of Fisher  concludeΧ2 of a slight subconscious tendency to favor the expected result in making tallies. Mendel was the first to count segregants at all. It is rather too much to expect that he would be aware of the precautions now known to be necessary for completely objective data. Anyone who doubts the difficulty in making repeatable counts should read chapter 5 in Pearl's Introduction to Medical Biometry. He reports an experiment in which 15 trained observers obtained extraordinary differences in sorting and counting the same 532 kernels of corn. Checking of counts that one does not like, but not of others, can lead to systematic bias toward agreement. I doubt whether there are many geneticists even now whose data, if extensive, would stand up wholly satisfactorily under the Χ2 test. “Mendel's perplexing ratios of round × angular and yellow × green… would hardly have been reported by one bent on fraud”. Wright concludes: “Taking everything into account, I am confident, however, that there was no deliberate effort at falsification.”Sewall Wright's  reactionSimilarly, Sturtevant : “PerhapWeiling  has examAssuming the sexuality of plants, the equivalence of pollen and ovule in the production of offspring and the self-evident transmission of plant traits over generations (“inheritance”), the following conclusions may be drawn from elementary Mendelism involving pairs of contrasting traits Fig..a having the property of becoming latent (“recessive”) in the hybrid dominated by the “domineering” A thus designated subsequently the dominant (partner) trait.Exponent: Number of traits; A and a are concrete material, particulate entities…Determinants of .…which are apparently assembled in (a pairwise manner) in hybrids without merger or loss of material integrity….…as shown by their intact individual reappearance  having overlooked, in his chosen field, experimental researches conclusive in their results, faultlessly lucid in presentation, and vital to the understanding not of one problem of current interest, but of many” ”. In retrospect, no one can disagree with this assessment of Mendel's work.Fisher , referriFrom the surviving records, the testimony of contemporaries and the evidence collected by historians closest to Mendel in time  it seems safe to conclude that above all Mendel was a “good” man in the best meaning of the word. Not just by ecclesiastical standards, Mendel being only one of many abbots in Western Catholicism, but first of all by the astonishing outpouring of grief at his death, for example, by his former students, fellow pedagogues and by the poor citizens of the town.formbildenden Elemente in the germ cells. This astonishing epistemological restraint made it so easy for his successors, for example, De Vries, Correns, Tschermak, Bateson…to take the next step to “genotype”.And what a legacy for an abbot (#) to bequeath to humanity, no hymns, no theological treatises, no sermons, no record of particular sanctity . Rather, a brief 47-page monograph on the progeny of plant hybrids, work conceived and executed over 10 years apparently without preconceived notions, and confined strictly to what we now call phenotypes and the behavior of their selected the best results from many. During the dreadful time of war after his presentations, the occupation of Brünn by some 50,000 Prussians in early 1866, and the ensuing cholera epidemic and food shortages Mendel had some time to reflect on his manuscript before its publication in mathematics to interpret biology was ahead of its time, having important parallels today in the use of computational biology to analyze big datasets. Mendel was a geneticist and genomicist malgré lui. In the 150 years since Mendel's oral presentations, we have taken the inferences drawn from his work so far as to begin an inventory of the genes in LUCA, an organism that lived some 3.6 billion years ago. LUCA became the ancestor of all living (and extinct) pro- and eukaryotes (Goldman et al. We agree with Olby ,1991 tha