Serial Killer Research Articles

Development of Next-Generation NK Cell Optimized Chimeric Antigen Receptors (CARs) for iPSC-Derived NK Cell Therapies Targeting Both Solid and Liquid Tumors

Chimeric Antigen Receptor (CAR) immunotherapy has transformed cancer therapeutics and has been successful in treating hematologic malignancies. To date, autologous T-cell therapy has been the major focus of CAR research and product development but has several limitations including high-cost and complexity of manufacturing, donor-to-donor variability, and severe toxicities in some patients. Allogenic natural killer (NK) cell therapies have also been shown to mount potent responses against hematologic malignancies, but unlike T-cell therapies are less likely to cause high-grade toxicities, such as cytokine release syndrome, neurotoxicity, or graft-vs-host-disease (GVHD), and therefore may serve as a preferred platform for CAR-enabled therapies. Several groups have demonstrated the clinical efficacy of CAR-expressing allogenic NK cells using CARs developed for T-cells (i.e., CD28 co-stimulatory domains). However, recent studies using NK cell activating receptor signaling modules (i.e., NKG2D and 2B4) as CAR signaling domains demonstrate increased activity compared to T-cell CARs, demonstrating the utility of NK optimized CARs. In addition, our previous studies showed that knocking out CIS (encoded by CISH gene), a key intracellular checkpoint of NK cell activation, in iPSC-derived NK cells (CISH KO iNK) significantly improved their anti-tumor activity, in vivo persistence, metabolic fitness, polyfunctionality and resistance to cell exhaustion. The goal of this study was to develop next-generation NK cell-optimized CARs designed to improve targeting and potency of our CISH KO iNK cell therapies against both hematologic malignancies and solid tumors. To achieve this, we developed a screening platform to identify novel CAR signaling domains derived from an array of immune cell signaling modules (Figure 1). First, we constructed a library of 44 CAR constructs (targeting CD19) containing signaling modules from diverse immune cell signaling receptors including NK cell activating receptors, cytokine receptors, and integrins. Next, we developed an efficient CAR expression protocol in iPSC-derived NK cells that yields high CAR expression (>75% CAR+) while maintaining high viability (>90%). We then screened for CAR activity using two co-culture target cell killing assays (eSight impedance assay and Caspase 3/7 killing assay) to test activity against two NK cell resistant CD19+ target cell lines (Raji and SupB15). Our screen identified 7 CAR signaling domains that performed better than both a T-cell CAR (CD28-CD28-CD3ζ) and previously reported NK cell optimized CARs (NKG2D-2B4-CD3ζ, CD28-OX40-CD3ζ, and CD28-OX40L-CD3ζ). These results were consistent across both functional assays and both target cell lines tested. To demonstrate the broad applicability of our top CAR construct (SLNK12) we generated SLNK12-CARs paired with antigen binding domains against various tumor antigens such as CD20, HER-2 etc. We confirmed that SLNK12-CARs potently kill target cell lines regardless of the antigen being targeted. To stringently test SLNK12-CAR potency, we conducted limiting dilution killing assays, serial killing assays, and 3D tumor spheroid killing assays. In all formats SLNK12-CAR iNK cells demonstrated better or comparable killing compared to previously reported NK cell optimized CAR NKG2D-2B4-CD3ζ (Figure 2). Current work is focused on validating our SLNK12-CARs using in vivo models. Overall, we have successfully developed a CAR screening platform in a therapeutically relevant allogenic cell source and have identified NK cell optimized CARs that enable increased potency of NK cells against both solid and liquid tumor cell lines including SKOV-3, BT474, SUP-B15, MOLT-4, Raji etc. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

FINGERPRINT MARKERS OF DELINQUENCY IN THE GROUP OF SERIAL KILLERS AND SUICIDES

The article is devoted to a comparative analysis of a number of combinations of types of papillary finger patterns, most characteristic of a group of serial killers and a group of suicides. It is established that combinatorics is most characteristic for both groups, in which the sum of the pattern codes of the index and middle fingers is equal to the value of the pattern code of the ring finger (right hand). The frequency of its occurrence in both comparison groups is 10%, which is about 10 times more frequent than in the control. Considering that papillary patterns are innate signs, the commonality of dermatoglyphic signs in serial killers and suicides indicates the influence of a biological factor on the likelihood of delinquent and deviant behaviors in humans (at least in some people).

Inhibition of Glucose Uptake Blocks Proliferation but Not Cytotoxic Activity of NK Cells.

Tumor cells often have very high energy demands. Inhibition of glucose uptake is therefore a possible approach to limit the proliferation and survival of transformed cells. However, immune cells also require energy to initiate and to maintain anti-tumor immune reactions. Here, we investigate the effect of Glutor, an inhibitor of glucose transporters, on the function of human Natural Killer (NK) cells, which are important for the immunosurveillance of cancer. Glutor treatment effectively inhibits glycolysis in NK cells. However, acute treatment with the inhibitor has no effect on NK cell effector functions. Prolonged inhibition of glucose uptake by Glutor prevents the proliferation of NK cells, increases their pro-inflammatory regulatory function and reduces the stimulation-dependent production of IFN-γ. Interestingly, even after prolonged Glutor treatment NK cell cytotoxicity and serial killing activity were still intact, demonstrating that cytotoxic NK cell effector functions are remarkably robust against metabolic disturbances.

An Interpretation of Clarice Starling in The Silence of the Lambs from the Perspective of Existentialist Feminism

The Silence of the Lambs, a suspense novel written by Thomas Harris in 1999, tells a story about a clever and courageous FBI agent, Clarice Starling, who overcomes difficulties caused by sexism and wins herself a reputation and honor by investigating a serial murder case. Since the novel was published, discussions about the plot and characters have never stopped. Nevertheless, research related to the protagonist Clarice Starling based on existentialist feminism are rare. This thesis takes Simone de Beauvoir’s existentialist feminism and the concept of “the other” to analyze gender inequalities encountered by Clarice Starling and her resistance against the patriarchal society. Therefore, combined with most women’s current living situation that gender inequality remains widespread, hindering their advance at work and in daily life, this thesis concludes that women should establish the subjective consciousness, prove their self-worth as females and avoid being “the other” through efforts.

Violence, crime, and psychiatry in the Spanish punk imaginary; General portrait

Previous findings suggest that the mass media depictions of people with mental disorders emphasize violence and criminality, unpredictable behaviour, and social incompetence. Our overall objective was to draw a general portrait of subcultural representations of criminal and violent behavior in the context of psychiatry. The content analysis of 190 song lyrics from a sample of 7777 outlined the elements composing the depictions of crime and violence and their connections with mental disorders in Spanish punk music (1981–2010). Two approaches were identified: one group of songs emphasized descriptions of violent and criminal behavior, while the other focused on psychiatric symptoms, syndromes, or diagnoses (appearing the violent or criminal behavior as epiphenomena of mental health problems). Quantitatively, songs with themes alluding to homicidal behavior predominated, with multiple homicide being widely portrayed. Regarding psychiatric disorders, substance use prevailed and, to a lesser extent, antisocial personality traits and psychotic symptoms. The depictions found are closely related to the connotations expected in the general population. Thus, we found a predilection for violent crimes and frequent allusions to the perpetrator as ‘mentally disturbed.’ It is consistent with the greater frequency of descriptions of violent crime in the media, despite its relative infrequency to other types of crime. Likewise, it coincides with the cultural interest in homicide and how it nourishes the current entertainment industry. However, some distinctive features in punk music included positive connotations for social deviance, and even antisocial traits, as a form of identity affirmation and opposition to the social order. On the other hand, violence and crime serve fundamentally punk provocativeness rather than a mythification or aesthetic enjoyment of crime. The portrayal of crime in the punk narratives was constructed around different non-exclusive sources whose contribution varied between compositions. It included the contents learned from and transmitted through the mass media, mainly the press, films, and television. These media provide both factual and fictional content (intertextuality). Other artistic manifestations can equally contribute to the interdiscursive ambit. The influence of crime news from abroad was relevant in depictions of mass murder (particularly, mass shootings), the same as intertextuality (mainly based on non-Spanish productions) for the subcultural portrayals of serial killers. Generally, the medical and criminological sciences have limited influence on the opinions of the general population, which continue to rely mostly on biased reports from mass media. This is a pending task for the scientific, academic, and clinical fields, hence the relevance of a dialogue between art, culture, media, and psychiatry.

Ludwig: a revolt against the modern world. The language and ideology of an Italian Neo-Nazi group in the Years of Lead

ABSTRACT The Ludwig group is usually described by the media as a group of serial killers operating in Italy during the so-called Years of Lead. The present article examines the structure and the nature of the group’s language through a multidimensional approach to rediscuss its current classification and description. The source material of the analysis is represented by the handwritten leaflets released by the group to claim its actions. The collected material, comprised of seven leaflets released by the Ludwig group in 1980–1984, has been examined through the analysis of language register, syntactic and rhetorical structure, adopted lexicon and co-occurrences. According to the analysis of the group’s language and messages it passed on, this paper suggests that the political nature of the Ludwig group receives its inspiration from Nazi ideology. The ideology that inspired the group’s violent actions must be brought back to Nazi Ideology, especially to the ideas of what is generally known as Esoteric Nazism.

PSYCHOLOGICAL PORTRAIT OF A SERIAL KILLER IN THE INTRASUBJECTIVE PERCEPTION OF THE ORDINARY CITIZEN

The topic of serial killers is incredibly relevant today, because these people appear everywhere and spread fear and death. Today it is unknown exactly who they are and how many lives have already been taken, and how many more will be taken… The exact number of victims, of some already caught and punished killers, is unknown. The difficulty is also in "hunting" for such people: until a pedantic and attentive maniac makes a mistake, it is difficult to catch him, because he is competent in how to plan the murder, so as not to leave evidence. Unfortunately, investigators, psychiatrists and psychologists still often misunderstand the thinking of such individuals, which directly affects the quality of the investigation process. Ukraine, as a democratic state, recognizes people, their life and health, honor and dignity, inviolability and security as its top priorities. In fact, this is the greatest social value. Everyone has the inalienable right to life. It is the legal protection of a person from criminal encroachments on life and health, as the most important social values, that the state should provide through its law enforcement agencies. We are in a state of prolonged military intervention amid an even longer pandemic with ever-increasing threats of social instability and existential personal and social crisis. All these factors increase the general state of increasing social aggression, which in turn can stimulate and stimulate (as recent events in Bucha and other places of hostilities show) people who are on the verge of pathological aggression to active action.
 Therefore, the chosen topic of our research, namely "Psychological portrait of a serial killer in the intrasubjective perception of the average citizen" may reveal new aspects of this problem.

The Uses of Mourning

The Uses of Mourning

Crime, history and the making of Operation Hyacinth: An interview with Marcin Ciastoń

Piotr Domalewski’s Operation Hyacinth (2021) centres on the young police officer Robert’s (Tomasz Ziętek) investigations into a case of serial murder and his developing romance with the student Arek (Hubert Miłkowski). The connective tissue is that all of the victims are gay men and Arek plays a role in it. As the film unfolds, we learn, alongside Robert, that the case is a massive cover-up operation and that his discoveries marry together his private and his professional lives. In this interview, I discuss, with writer Marcin Ciastoń, his extensive research for the film, which was inspired by historical events; and Robert’s and Arek’s romance. We explore how, if on the one hand, Arek represents rebellion to Robert, then, on the other, Robert is the embodiment of reticence, and we attend to a key scene wherein Robert is pressured by his father (Marek Kalita), also a police officer, into questioning Arek about his sexual history. All of the characters appear to be on trial, and as Ciastoń declares, ‘[e]veryone involved had a secret’. This interview advances scholarship by recovering the critical project that directly informs this imaginative one, by suggesting its importance in LGBTQ history and by attending to Ciastoń’s approach to personal and public histories.

Could Serial Killing Actually Be Addictive? A Close Examination of Compulsion and Escalation in the Jeffrey Dahmer Case

Could Serial Killing Actually Be Addictive? A Close Examination of Compulsion and Escalation in the Jeffrey Dahmer Case

“Forging a New Language”

This article examines James Baldwin’s late text The Evidence of Things Not Seen (1985) as one of his substantial attempts at “forging a new language,” which he tentatively mentions in his late essays and interviews. As an unpopular and difficult text in Baldwin’s oeuvre, Evidence carries the imprint of a new economy of time, casting the past into the present, and a new economy of space, navigating across other geographies in appraising the serial killings of children in one of Atlanta’s poorest Black neighborhoods. This article suggests that a new economy of time emerges earlier in No Name in the Street (1972), as a result of Baldwin’s self-imposed exile in Europe. The article then analyzes his spatiotemporal logic in the specifics of Evidence with reference to a Black middle class, urbanization, the ghetto, gentrification, and other colonized spaces.

Staged body disposal sites and homicide: Investigating the multivariate approach of a serial killer

AbstractWhilst crime scene staging in homicide, as an attempt to avoid detection, has attracted some scholarly attention in recent years, staging a body disposal site has not been similarly scrutinised. Indeed, whilst some statistical studies note moving a homicide victim's body as a distinct crime scene behaviour, there is little discussion or analysis of body disposal sites generally. This case seeks to illustrate how a body disposal site may be staged—in three different forms—and to supplement existing quantitative data on offender behaviours undertaken to avoid detection. In so doing, a new category of staging is proposed: staging a body disposal site.

Non-cytotoxic functions of CD8 T cells: "repentance of a serial killer".

Cytotoxic CD8 T cells (CTLs) are classically described as the “serial killers” of the immune system, where they play a pivotal role in protective immunity against a wide spectrum of pathogens and tumors. Ironically, they are critical drivers of transplant rejection and autoimmune diseases, a scenario very similar to the famous novel “The strange case of Dr. Jekyll and Mr. Hyde”. Until recently, it has not been well-appreciated whether CTLs can also acquire non-cytotoxic functions in health and disease. Several investigations into this question revealed their non-cytotoxic functions through interactions with various immune and non-immune cells. In this review, we will establish a new classification for CD8 T cell functions including cytotoxic and non-cytotoxic. Further, we will discuss this novel concept and speculate on how these functions could contribute to homeostasis of the immune system as well as immunological responses in transplantation, cancer, and autoimmune diseases.

Serial murder in medical clinics and care homes.

Background Serial murder in clinics and care homes have gained attention more than once in recent years. The strong yet quickly fading public outrage has not yet led to well-founded professional and health-political engagement with the topic. With few systematic studies conducted, knowledge about perpetrator-related and environment-related risk factors in the day-to-day context of healthcare is sparse. Methods Court cases of serial murder in clinics and care homes in Germany, Austria, and Switzerland that were concluded with a final verdict by February 2022 were investigated. Research materials consisted of court documents and observations made during the trials. The cases were evaluated with regard to the victims, crime scenes, methods of killing, perpetrators, and perpetrator motives. 12 serial murders involving 17 perpetrators were included in this study. Results Perpetrator-specific early warning signs included a pronounced insecurity in combination with a striving for prestige and power, which were accompanied by a loss of empathy. Reactions of the colleagues and supervisors of the perpetrators in the immediate professional environment included misjudgement, concern about one’s own disadvantages, feared damage to the reputation of the institution, and insufficient willingness to clarify the situation. As a result, many initial murders went unsuspected and unreported so that the frequency of the criminal activity and the number of victims increased over time. Conclusion More information about serial murder in clinics and care homes is necessary. Research efforts are needed to better assess the prevalence of such crimes and to develop appropriate preventive measures. Circumstances that enable such acts, risk factors, perpetrator profiles, and early-stage countermeasures must be comprehensively addressed in the context of education, training and further education.

Serial Murder as Modernist Ritual

Abstract This essay argues that the serial murderer's rituals are homologous to those that structure the more quotidian or administrative, but equally sadistic, forms of violence against fungible bodies in US civil society. At stake in this homology is recognizing that the sadism publics so readily associate with the depraved serial killer are present in the many cruelties that such publics enthusiastically condone and enjoy. Serial murder is a modernist ritual among many others, and its capacity to induce affective investment from consuming publics, just as surely as the killer himself, is a function of what I am calling sadistic form. To clarify this argument, the essay reads serial killer Ted Bundy's many crimes as ritualistic enactments of sadistic form, as well as the varied responses during his 1989 execution. In so doing, I illustrate how different rituals function to obscure or amplify the sadism to which they give expression.

Subcultural Representations of Perpetrators and Victims of Crime and Violence Associated with Mental Disorders

Introduction and objectivesThe beliefs and opinions of the general population are based substantially on mass media, which often equates mental disorders with violence and criminality. These stigmatising depictions contribute to the development and persistence of negative attitudes towards people with psychiatric conditions. The objective was to examine, through popular music, the subcultural representations of crime and violence in the context of mental disorders, focusing on depictions of victims and offenders. MethodsStrategy of analysis: Content analysis of Spanish punk lyrics (1981-2010) with references to violent and criminal behaviour associated with mental disorders. Results257 Spanish punk bands were identified. The discographies included 7,777 songs, of which 190 were related to aggression, violence, or crime. A predilection for violent crimes and descriptions of the perpetrator as “mentally disturbed” was observed. Although they were present, psychotic symptoms were not the main psychiatric symptoms associated with violent crime, but instead it was substance use, antisocial personality traits and paraphilic behaviour. There was less attention paid to victims than to perpetrators. ConclusionsThe relationships between mental disorders and criminality/violence are overemphasised in the analysed subculture. A positive connotation of social deviance and violent content (particularly serial murder) in service to the provocative nature of this type of music was observed.

Home Is Where the Horror Is (2022)

Home Is Where the Horror Is (2022) Jason Zinoman (bio) Sometimes facing your fears isn't enough. You have to scrutinize them. In an attempt to understand my own nightmares—and the ones that shaped our culture—my first book, Shock Value, published a decade ago, examined one of the great eras of modern film: the revolutionary scary movies made between the late 1960s through the end of the following decade.1 I called them the New Horror. To tell the story of its artists—masters such as Wes Craven, Tobe Hooper, John Carpenter, and Dan O'Bannon among many others—I interviewed them about their work with an ear sensitive to what this group shared. One surprisingly common thing I discovered was an embarrassment about working in the genre itself. To the people who made Halloween (Carpenter, 1978) and Alien (Scott, 1979) horror, as they had understood it since they were young, was lowbrow, disreputable, the kind of thing you didn't want to tell your parents about. To hear these great artists tell it, the genre they worked in was kid's stuff. Sadly, most of the filmmakers I wrote about in the book have died, but part of their considerable legacy is to change the reputation of horror and consequently the atmosphere that their successors work in. The genre is not only bigger and more lucrative, a persistently popular part of the cultural diet, but also more respected. For young filmmakers, there is no shame in working in the genre of The Texas Chain Saw Massacre (Hooper, 1974). There are downsides to the growing stature of horror, to be sure, but also [End Page 289] advantages, a new sense of the possible that allows for growth. The recent expansion of the genre is what inspired the article below, which I wrote for the cover of the "Arts & Leisure" section of the New York Times in 2018 about the artists at the forefront of an ambitious new direction in horror. Building on the work of their predecessors, their work appears unshackled from any status anxiety over genre and deals directly and expansively in mature themes. They are making movies that kids enjoy but are primarily aimed at adults. Since I wrote the article this trend has only intensified, and its impact is evident in recent movies such as Relic (James, 2020) and She Dies Tomorrow (Seimetz, 2020) that speak to the terror of isolation in the age of COVID-19 better than any new mainstream dramas. This new grown-up horror has produced movies that I believe will be studied and imitated just like those from the 1970s were. This essay, and the others in this journal, attempt to understand this new golden age. _____ What happens when your family is what frightens you? A new renaissance in scary movies skips jump scares in favor of dread based on adult fears. In Hereditary (Aster, 2018), bugs crawl from decapitated heads, ghosts lurk in the shadows, and an artist tries to communicate with the dead. But the most jarring moment of this terrifying new movie might be when Annie, a mother played by Toni Collette, tells her son she never wanted to have him and tried to induce a miscarriage. Then she wakes from this nightmare, unsettled by the thoughts rattling in her subconscious. Parental guilt is the real monster here. Moving into territory once the preserve of prestige dramas, horror has never been more bankable and celebrated than it is right now. And while evil clowns and serial killers at sorority houses still haunt young viewers (and make tons of money), we're in the midst of a golden age of grown-up horror. Hushed and characterdriven, this mix of indie fare and blockbusters works ferociously on adult anxieties in an age of dislocation. These movies have confronted liberal racism, economic worries, and family dysfunction, and while horror has always reflected the social and political concerns of its day, if you had to pinpoint a unifying theme that distinguishes this renaissance, it's the ominous danger of overwhelming grief. A character coping with the death of a loved one is the new car of teenagers heading to a...

Event Analysis; Analysis of Jeffery Dahmer (A.K.A Milwaukee Cannibal)

Sexual homicides, although rare attract a great deal of attention from the media, the general public, and, more recently, the academic community, they are devastating crimes and have the potential for repetition. A case study of Jeffery Dahmer, Milwaukee Cannibal sexual homicide was analyzed for the purpose of this research. Clinicians are often caught in the dilemma of helping offenders succeed in a society that will not allow them to achieve success and may actively conspire against successful reintegration. Despite the vast knowledge about serial killers, it is still uncertain why they kill. Undoubtedly, many factors enable individuals to perform such acts without remorse, including biological and neuropsychological factors, such as being bombarded by images that glamorize violence daily. Thus, the clinician/ social workers must struggle to find ways to help his or her clients practice their new skills in a society that does not want the offender and takes active steps to ostracize and humiliate offenders, which in turn leads to former offenders experiencing further isolation and a loss of hope.

Multidimensional single-cell analysis identifies a role for CD2-CD58 interactions in clinical antitumor T cell responses.

The in vivo persistence of adoptively transferred T cells is predictive of antitumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific chimeric antigen receptor (CAR) T cells as the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on time-lapse imaging microscopy in nanowell grids (TIMING), which integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with multifunctionality. We showed that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed that elevated CD58 expression on pretreatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T cell–tumor cell interactions in identifying optimal antitumor responses.

Statistical Issues in Serial Killer Nurse Cases

We study statistical aspects of the case of the British nurse Ben Geen, convicted of 2 counts of murder and 15 of grievous bodily harm following events at Horton General Hospital (in the town of Banbury, Oxfordshire, UK) during December 2013–February 2014. We draw attention to parallels with the cases of nurses Lucia de Berk (the Netherlands) and Daniela Poggiali (Italy), in both of which an initial conviction for multiple murders of patients was overturned after the reopening of the case. We pay most attention to the investigative processes by which data, and not just statistical data, is generated; namely, the identification of past cases in which the nurse under suspicion might have been involved. We argue that the investigation and prosecution of such cases are vulnerable to many cognitive biases and errors of reasoning about uncertainty, exacerbated by the fact that fact-finders have to determine not only whether a particular person was guilty of certain crimes, but whether any crimes were committed by anybody at all. The paper includes some new statistical findings on the Ben Geen case and suggests further avenues for investigation. The experiences recounted here have contributed to the writing of the handbook Healthcare Serial Killer or Coincidence? Statistical Issues in Investigation of Suspected Medical Misconduct, Royal Statistical Society, London, 2022.