Doctor of Philosophy(PhD) / From Federation in 1901 through the first three decades of the twentieth century there was a perceptible shift in modes of rule in New South Wales (NSW) related to the management of venereal diseases. At the beginning of the twentieth century a medicopenal approach was central. By 1925, persuasion and ‘responsibilisation’ were becoming important modes, and young people rather than ‘case-hardened prostitutes' were assessed as being a ‘venereal’ risk. Framing this period were three important legislative developments which informed, and were informed by, these shifts: the NSW Prisoners Detention Act 1909, the NSW Select Committee into the Prevalence of Venereal Diseases 1915 and the NSW Venereal Diseases Act 1918. At its core this thesis is concerned with examining shifting modes of rule. This thesis closely examines each. I suggest that these modes of rule can be viewed through the lens of biopolitics, and following Foucault, deploy the ‘medical gaze’ and the ‘watchful eye’ as constructs to examine the relationship between the government of self, government of others and government of the state. I use the medical gaze to describe not only the individual venereal patient attending a hospital and the body of the patient diagnosed with syphilis and/or gonorrhoea, but most importantly to describe the power relationship between the medical practitioner, the teaching hospital and the patient. I use the watchful eye in a more overarching way to suggest the suite of techniques and apparatus deployed by government to monitor and regulate the venereal body politic, both the populations perceived to be posing a venereal risk, and populations at risk of venereal infection. In relation to the venereal body and the venereal body politic, I analyse three fundamental aspects of the management of venereal diseases: treatment, prevention and epidemiology. Treatment: Over this period, treatment moved from lock institutions to outpatient clinics. Embodied in this change was a widespread institutional ambivalence towards treating venereal patients. I contend that treatment of venereal diseases was painful, prolonged and punitive precisely because of the moral sickness perceived to be at the iv heart of venereal infection. I track this ambivalence to a systemic fear of institutional ‘venerealisation’, which decreased perceptibly across the period. Closely analysing surviving patient records, I argue that in their conduct, venereal patients were often compliant, conscientious and responsible. Prevention: I argue that preventative approaches to venereal diseases became increasingly complex, and operated in three domains – preventative medicine (diagnosis, treatment and vaccination); public health prevention (notification, isolation and disinfection); and prevention education (social purity campaigns and sex hygiene). An emerging plethora of community-based organisations and campaigns began to shift the sites and practices of power. Epidemiology: I suggest that there was a shift from danger to risk in the conceptualisation of venereal diseases. This shift necessitated a focus on factors affecting populations, as opposed to factors affecting individuals. This in turn led to the deployment of various techniques to monitor the conduct of venereal populations. The NSW Venereal Diseases Act 1918 created two important new venereal categories: the ‘notified person’ and the ‘defaulter,’ both of which came to permeate renditions of venereal patients throughout the 20th century.

Doctor of Philosophy(PhD) / From Federation in 1901 through the first three decades of the twentieth century there was a perceptible shift in modes of rule in New South Wales (NSW) related to the management of venereal diseases. At the beginning of the twentieth century a medicopenal approach was central. By 1925, persuasion and ‘responsibilisation’ were becoming important modes, and young people rather than ‘case-hardened prostitutes' were assessed as being a ‘venereal’ risk. Framing this period were three important legislative developments which informed, and were informed by, these shifts: the NSW Prisoners Detention Act 1909, the NSW Select Committee into the Prevalence of Venereal Diseases 1915 and the NSW Venereal Diseases Act 1918. At its core this thesis is concerned with examining shifting modes of rule. This thesis closely examines each. I suggest that these modes of rule can be viewed through the lens of biopolitics, and following Foucault, deploy the ‘medical gaze’ and the ‘watchful eye’ as constructs to examine the relationship between the government of self, government of others and government of the state. I use the medical gaze to describe not only the individual venereal patient attending a hospital and the body of the patient diagnosed with syphilis and/or gonorrhoea, but most importantly to describe the power relationship between the medical practitioner, the teaching hospital and the patient. I use the watchful eye in a more overarching way to suggest the suite of techniques and apparatus deployed by government to monitor and regulate the venereal body politic, both the populations perceived to be posing a venereal risk, and populations at risk of venereal infection. In relation to the venereal body and the venereal body politic, I analyse three fundamental aspects of the management of venereal diseases: treatment, prevention and epidemiology. Treatment: Over this period, treatment moved from lock institutions to outpatient clinics. Embodied in this change was a widespread institutional ambivalence towards treating venereal patients. I contend that treatment of venereal diseases was painful, prolonged and punitive precisely because of the moral sickness perceived to be at the iv heart of venereal infection. I track this ambivalence to a systemic fear of institutional ‘venerealisation’, which decreased perceptibly across the period. Closely analysing surviving patient records, I argue that in their conduct, venereal patients were often compliant, conscientious and responsible. Prevention: I argue that preventative approaches to venereal diseases became increasingly complex, and operated in three domains – preventative medicine (diagnosis, treatment and vaccination); public health prevention (notification, isolation and disinfection); and prevention education (social purity campaigns and sex hygiene). An emerging plethora of community-based organisations and campaigns began to shift the sites and practices of power. Epidemiology: I suggest that there was a shift from danger to risk in the conceptualisation of venereal diseases. This shift necessitated a focus on factors affecting populations, as opposed to factors affecting individuals. This in turn led to the deployment of various techniques to monitor the conduct of venereal populations. The NSW Venereal Diseases Act 1918 created two important new venereal categories: the ‘notified person’ and the ‘defaulter,’ both of which came to permeate renditions of venereal patients throughout the 20th century.

Malignant melanoma is one of the most rapidly increasing cancers and accounts for about three-quarter of all skin cancer deaths worldwide. Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge how various wavelength spectra affect the balance between proliferation and apoptosis controlling the homeostasis of the melanocyte population is still limited. The aim of this thesis was to elucidate the regulation of UVA/B induced apoptotic signaling in human epidermal melanocytes in vitro in relation to redox alterations and antioxidant photoprotection. UVA irradiation induced changes in plasma membrane stability, decreased cell proliferation and increased apoptosis. In comparison, melanocyte plasma membrane was markedly resistant to UVB irradiation although apoptosis was triggered. Thus, UVA irradiation should not be overlooked as an etiologic factor in melanoma development. Further, after irradiation with UVA/B we found alterations in redox state manifested by a reduction of intracellular GSH levels, translocation of nuclear factor-κB from the cytosol to the nucleus, an increase of γ-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and an increased apoptosis frequency. α-Tocopherol provided photoprotection through several modes of action affecting redox alterations and signaling, stabilizing the plasma membrane, and decreased proliferation and apoptosis rate, while β-carotene did not show the same protective capacity. Altogether, α-tocopherol might be a useful substance in protecting melanocytes from UV induced damage. We demonstrate UVA/B irradiation to activate the intrinsic pathway of apoptosis in melanocytes where translocation of Bcl-2 family proteins to the mitochondria modulates the apoptosis signal. Interestingly, the anti-apoptotic Bcl-2 family proteins generally thought to be attached to membranes, were localized in the cytosol before UV irradiation and translocated to the mitochondria in the surviving population, which might be a critical event in preventing apoptotic cell death. Lysosomal cathepsins were released to the cytosol acting as pro-apoptotic mediators upstream of activation and translocation of Bax to the mitochondria. When melanocytes were exposed to UVA, p53 participated in apoptosis regulation through interaction with Bcl-2 family proteins, while UVB induced p53-transcriptional activity and apoptosis involving lysosomal membrane permeabilization. Thus, depending on the UV wavelength p53 mediated apoptosis in melanocytes by transcriptional dependent or independent activity. These results emphasize p53 as an important pro-apoptotic component in the regulation of apoptosis. This thesis gives new insight in the harmful and various effects of different wavelengths within the UV spectrum on human melanocytes in vitro. Improved knowledge of the apoptosis regulatory systems in melanocytes might lead to a better understanding of the formation of pigment nevi and malignant melanoma and, in the future, provide better strategies to prevent and eliminate tumor development and progression.

Malignant melanoma arises from the pigment producing melanocytes in epidermis and is the most aggressive type of skin cancer. The incidence of malignant melanoma is increasing faster than any other type of cancer in white population worldwide, with a doubling rate every 10-20 years. So far, the only identified external risk factor for malignant melanoma is UV exposure. Elimination of photodamaged cells by apoptosis (programmed cell death) is essential to prevent tumor formation. Melanocytes are considered relatively resistant to apoptosis, however, the regulation of apoptosis in melanocytes is still unknown. The aim of this thesis was to investigate the apoptotic process following ultraviolet (UV) irradiation in primary cultures of human melanocytes. Focus was on regulation of mitochondrial stability by Bcl-2 family proteins and the possible participation of lysosomal proteases, cathepsins. UV irradiation activated the mitochondrial pathway of apoptosis, leading to cytochrome c release, caspase activation, and nuclear fragmentation. No change in protein expression of Bax and Bcl-2 was observed in response to UV. Instead, translocation of the Bcl-2 family proteins from cytosol to mitochondia was important in the regulation of survival and death of melanocytes. The findings further demonstrated permeabilization of the lysosomal membrane to occur early in the apoptotic process, resulting in cathepsin release into the cytosol. The cathepsins were potent pro-apoptotic mediators and triggered apoptosis upstream of Bax translocation and mitochondrial membrane permeabilization. In response to both heat and UV irradiation, there was a marked increase in expression of stress-induced heat shock protein 70 (Hsp70), which inhibited apoptosis by binding lysosomal and mitochondrial membranes and counteracting the release of cathepsins and cytochrome c. Furthermore, UV irradiation activated c-jun N-terminal kinase (JNK), which triggered apoptosis upstream of cathepsins release from the lysosomes. In addition, JNK mediated apoptosis through phosphorylation of pro-apoptotic Bim, which was released from anti-apoptotic Mcl-1, by UV induced Mcl-1 depletion. This thesis illustrates that permeabilization of mitochondria and lysosomes and release of their constituents to the cytosol participates in UV induced apoptosis signaling in human melanocytes in vitro. The process is regulated by a complex network of pro- and anti-apoptotic proteins, exerting their effects through intracellular translocation and alteration of protein expression.

Introduction. Plaque psoriasis (psoriasis vulgaris) is a chronic disease and the most common type of psoriasis. It is charactarized by well-defined areas with silvery scaling, erythema, puritus and sometimes pain. Psoriasis affects about 1.5 - 3 % of the world population. Patients with psoriasis often suffer with comorbidies which makes drug therapy essential in relieving symptoms. Mild to moderate disease is treated with topical therapy such as corticosteroids and retinoid creams and with phototherapy. More severe disease is treated with systemic therapy e.g. methotrexate, cyclopsorine and retinoids. Patients who do not respond well to these treatments can be put on antibody therapy, e.g., secukinumab. Secukinumab is a monoclonal antibody that specifically targets the IL-17A. It is used to treat moderate to severe psoriasis. Secukinumab binds to IL-17A and inhibits it to interact with IL-17R. This leads to downregulation of immune response and symptom relieving. Other monoclonal antibodies that are used are risankizumab that binds to the p19 subunit of IL-23 and ustekinumab that binds to the p40 subunit of IL-12 and IL-23. Clinical psoriasis symptoms are evaluated with the Psoriasis Area Severity Index (PASI) from 0 till 72 and with the Inverstigator’s Global Assessment (IGA) from 0 till 5. Method. This thesis is a literature review with an aim to evaluate the efficacy and safety of secukinumab in treating psoriasis vulgaris. The search for articles was done in PubMed with the search words ‘’secukinumab’’ and ‘’plaque psoriasis’’. Included articles were RCT-studies published between 2014 and 2022. Moreover, these studies used the PASI and the IGA scoring system. This thesis excluded studies with children. Overall, this thesis included 6 trials reported in 5 articles. Results. The trials ERASURE, FIXTURE and CAIN demonstrated that 300 mg and 150 mg secukinumab per day were effective in treating moderate to severe psoriasis vulgaris compared to  placebo and etarnecept. The trials CLARITY and CLEAR demonstrated that 300 mg secukinumab was effective in treating moderate to severe psoriasis vulgaris compared to ustekinumab. The trial IMMerge demonstrated that risankizumab was superior in treating psoriasis vulgaris compared to secukinumab. Most of the adverse effects were mild and moderate and the most common reported were nasopharyngitis, upper respiratory tract infection, diarrhea and headache.Conclusion. Secukinumab demonstrates good efficacy and safety in the treatment of moderate to severe psoriasis in patients who have not received a satisfactory result from other drugs therapies.

No description available.

Melanoma is one of the deadliest forms of cancer. Unfortunately, its incidence rates have been increasing all over the world. One of the techniques used by dermatologists to diagnose melanomas is an imaging modality called dermoscopy. The skin lesion is inspected using a magnification device and a light source. This technique makes it possible for the dermatologist to observe subcutaneous structures that would be invisible otherwise. However, the use of dermoscopy is not straightforward, requiring years of practice. Moreover, the diagnosis is many times subjective and challenging to reproduce. Therefore, it is necessary to develop automatic methods that will help dermatologists provide more reliable diagnoses.  Since this cancer is visible on the skin, it is potentially detectable at a very early stage when it is curable. Recent developments have converged to make fully automatic early melanoma detection a real possibility. First, the advent of dermoscopy has enabled a dramatic boost in the clinical diagnostic ability to the point that it can detect melanoma in the clinic at the earliest stages. This technology’s global adoption has allowed the accumulation of extensive collections of dermoscopy images. The development of advanced technologies in image processing and machine learning has given us the ability to distinguish malignant melanoma from the many benign mimics that require no biopsy. These new technologies should allow earlier detection of melanoma and reduce a large number of unnecessary and costly biopsy procedures. Although some of the new systems reported for these technologies have shown promise in preliminary trials, a widespread implementation must await further technical progress in accuracy and reproducibility.  This thesis provides an overview of our deep learning (DL) based methods used in the diagnosis of melanoma in dermoscopy images. First, we introduce the background. Then, this paper gives a brief overview of the state-of-art article on melanoma interpret. After that, a review is provided on the deep learning models for melanoma image analysis and the main popular techniques to improve the diagnose performance. We also made a summary of our research results. Finally, we discuss the challenges and opportunities for automating melanocytic skin lesions’ diagnostic procedures. We end with an overview of a conclusion and directions for the following research plan.

Hansson, L. Detektion av makrolidresistens hos Mycoplasma genitalium med Panther Fusion. Examensarbete i biomedicinsk laboratorievetenskal 15 högskolepoäng. Malmö universitet: Fakulteten för hälsa och samhälle, institutionen för Biomedicinsk Vetenskap, 2023.   Mycoplasma genitalium är en sexuellt överförbar mikroorganism som infekterar både män och kvinnor, som behandlas oftast med azitromycin med ett ökande problem av antibiotikaresistens. För M. genitalium är makrolidresistens det främsta hotet mot behandling, och har kopplats till fyra punktmutationer i region V i 23S rRNA-genen: A2071G, A2072G, A2072C samt A2071T (M. genitalium G-37, GenBank NR_077054.1). Projektet har undersökt möjligheten att ersätta nuvarande in house realtids-PCR metod för makrolidresistensbestämning med ett integrerat nukleinsyra-reningssteg och realtids-PCR med Panther Fusion (Hologic) hos Klinisk mikrobiologi i Lund. Under projektet analyserades 55 patientprover som samlades under perioden januari-februari 2023 i Region Skåne, som blivit positiva vid M. genitalium testning. Dessa prover har därefter analyserats av personal med nuvarande ABI-metod för resistensbestämning och sedan analyserats på Panther Fusion. Nuvarande ABI-metod resulterade i positiv signal för 91% (50/55) av patientprover positiva vid M. genitalium analys och makrolidresistensmutation hos 25 % (14/55), medan Panther Fusion metoden resulterade i positiv signal för 81 % (45/55) av positiva M. genitalium prover och påvisade resistensmutation hos 20 % (11/55) av proverna.

Quantification of progesterone and 17-β estradiol in mouse serum by liquid chromatography-tandem mass spectrometry Authors: Benjamin Kennard, Allison Cobble, Amy Gravitte, Keleigh Galloway, Jen Kintner, Jennifer Hall, Stacy Brown Introduction: In the United States, Chlamydia trachomatis is a commonly appearing sexually transmitted infection1. It affects the U.S. healthcare system to a tune of about $500 million dollars annually2. In women, it generally appears asymptomatic and can lead to severe secondary complications such as pelvic inflammatory diseases or infertility1. Female sex hormones, estrogen and progesterone, are being identified to have a role in chlamydial infection. Specifically, this study aims to create quantification methods to detect levels of estrogen and progesterone in mice, infected with Chlamydia muridarum, plasma samples. Methods: Progesterone samples were prepared using solid-liquid extraction (SLE+) cartridges with ethyl acetate as the elution solvent. Estradiol samples were prepared using liquid-liquid extraction (LLE) with methyl tert-butyl ether and subsequent derivatization with DMIS. Following sample preparation, hormones were quantified in samples using LC-MS/MS with a gradient elution of 1 mM ammonium fluoride in water and acetonitrile. The separation was achieved using a UCT C18 column (100 x 21.mm, 1.8 μm particle size) maintained at 50oC. The mass spectrometer was set up to isolate molecular ions for progesterone (m/z 315.0910) and derivatized estradiol (m/z 431.1835). Quantification was facilitated by the use of deuterium-labeled internal standards and their corresponding molecular ions in the mass spectrometer (d9-progesterone; m/z 324.1230 and d5-estradiol; m/z 436.2922). Results: Several aspects of the assay presented have been optimized for maximum analyte recovery and analytical sensitivity, including column choice, mobile phase, derivatizing agents for estradiol, and extraction protocols for progesterone. The LC-MS/MS method was investigated for precision and accuracy over three separate days. The dynamic range of the progesterone assay was 5 – 100 ng/mL, with a limit of detection of 1 ng/mL. Likewise, the estradiol assay was linear in the range of 5 – 100 ng/mL, with a limit of detection of 0.5 ng/mL. The average precision, represented by % RSD was 0.74 – 8.5% and 6.3 – 13.4% for progesterone and estradiol, respectively. The accuracy of the method, represented by % error was 1.6 – 14.4% and 4.0 – 10.5% for progesterone and estradiol, respectively. Successful validation was defined as < 15% RSD and error (< 20% at the limit of quantification), per current FDA Guidelines. Conclusions: The developed LC-MS/MS method is specific for progesterone and estradiol, and the extraction is suitable for preparation of mouse serum samples. This assay could be successfully applied to hormone quantification in mouse samples to support the investigation of the link between chlamydia infection and hormone levels in female animals. References 1. Chlamydia - 2017 Sexually Transmitted Diseases Surveillance. https://www.cdc.gov/std/stats17/chlamydia.htm. Accessed October 23, 2018. 2. Owusu-Edusei K, Chesson HW, Gift TL, et al. The Estimated Direct Medical Cost of Selected Sexually Transmitted Infections in the United States, 2008. Sex Transm Dis. 2013;40(3):197-201. doi:10.1097/OLQ.0b013e318285c6d2

I denna uppsats har jag undersökt hur den svenska arbetarförfattaren Ivar Lo-Johansson (1901–1990) beskriver könssjukdomar i romanen Kungsgatan (1935). Lo-Johansson smittades själv av gonorré i början av 1930-talet och kände därför som författare att han hade ett syfte att göra detta ämne lite mindre tabu. Han skulle dock inte berätta om sin sjukdom för någon under denna tid. En stor del av uppsatsen kommer ägnas åt hur romanen mottogs i den samtida pressen. Jag har försökt bevisa – tvärtemot vad som flera litteraturvetare och även författaren själv gjort tidigare – att romanen inte kan klassas som en skandalroman som fick uteslutande negativ kritik på grund av dess två huvudteman prostitution och könssjukdomar.  Den vanligaste åsikten bland litteraturkritiker var att romanen generellt kraftigt borde kortats ner innan utgivning. / In this paper, I have analyzed how the Swedish proletarian writer Ivar Lo-Johansson (1901–1990) describes venereal diseases in his novel Kungsgatan (1935). Lo-Johansson contracted gonorrhea during the early 1930s, and because of this, he felt he had a social purpose as an author to make this subject a little less taboo. He would not, however, reveal his case for anybody during this period. A significant part of this paper will be dedicated to the initial critical reception of Kungsgatan. I have tried to prove – in contrast to previous scholars, even the author himself – that the novel in the beginning wasn’t regarded as scandalous by most literary critics, nor it wasn't criticized because of its main themes: prostitution and venereal diseases. Rather, the most common opinion by critics was that the novel in general should have been shortened down heavily before publication.