Risk factors for oral cancer, a retrospective study among an Indian population

ABSTRACT Degree project, Programme in Medicine Risk factors for oral cancer, a retrospective study among an Indian population. Lars Wennerström, University of Gothenburg, Sweden 2016. Introduction Oral cancer or oral squamous cell carcinoma (OSCC) is among the most common types of cancer in India and strongly linked to habits like smoking- and smokeless tobacco, alcohol and Areca nut chewing. In the western world an increasing number of HPV-positive OSCCs are diagnosed and differences in the expression of the immune system indicates that the pathogenesis of HPV-positive and HPV-negative OSCC differs. Aims To evaluate risk factors that increase the risk for malignancy in the oral cavity. Methods Patients were recruited from Kannur Dental College and asked to answer a question form about risk habits and medical history. The patients were then examined by a dentist and if appropriate, tissue samples were collected for later analysing. Results 19 patients were included in the study. Data analysing only showed significance for smokeless tobacco in combination with areca nut (P-value=0.021) as a habit that increases the odds (OR= 18.667) for presenting an OSCC. No tissue swabs were analysed during the timeframe for the thesis Conclusions The results for smokeless tobacco and Areca nuts highlight the need for a stricter policy (or stricter implementation of the existing policy) to reduce the numbers of users. The negative results for the other habits is most likely due to the small number of patients included in the study

Comment on "Spin-1 aggregation model in one dimension"

M. Girardi and W. Figueiredo have proposed a simple model of aggregation in one dimension to mimic the self-assembly of amphiphiles in aqueous solution [Phys. Rev. E 62, 8344 (2000)]. We point out that interesting results can be obtained if a different set of interactions is considered, instead of their choice (the s=1 Ising model).Comment: Accepted for publication in Phys. Rev.

Ecological connectivity of the marine protected area network in the Baltic Sea, Kattegat and Skagerrak: Current knowledge and management needs

Marine protected areas (MPAs) have become a key component of conservation and fisheries management to alleviate anthropogenic pressures. For MPA networks to efficiently promote persistence and recovery of populations, ecological connectivity, i.e. dispersal and movement of organisms and material across ecosystems, needs to be taken into account. To improve the ecological coherence of MPA networks, there is hence a need to evaluate the connectivity of species spreading through active migration and passive dispersal. We reviewed knowledge on ecological connectivity in the Baltic Sea, Kattegat and Skagerrak in the northeast Atlantic and present available information on species-specific dispersal and migration distances. Studies on genetic connectivity are summarised and discussed in relation to dispersal-based analyses. Threats to ecological connectivity, limiting dispersal of populations and lowering the resilience to environmental change, were examined. Additionally, a review of studies evaluating the ecological coherence of MPA networks in the Baltic Sea, Kattegat and Skagerrak was performed, and suggestions for future evaluations to meet management needs are presented

Baltic Sea genetic biodiversity: Current knowledge relating to conservation management

1. The Baltic Sea has a rare type of brackish water environment which harbours unique genetic lineages of many species. The area is highly influenced by anthropogenic activities and is affected by eutrophication, climate change, habitat modifications, fishing and stocking. Effective genetic management of species in the Baltic Sea is highly warranted in order to maximize their potential for survival, but shortcomings in this respect have been documented. Lack of knowledge is one reason managers give for why they do not regard genetic diversity in management. 2. Here, the current knowledge of population genetic patterns of species in the Baltic Sea is reviewed and summarized with special focus on how the information can be used in management. The extent to which marine protected areas (MPAs) protect genetic diversity is also investigated in a case study of four key species. 3. Sixty‐one species have been studied genetically in the Baltic Sea, but comprehensive genetic information exists for only seven of them. Genetic monitoring shows genetic stability in some species but fluctuations and genetic changes in others. About half of the scientific studies published during the last 6 years provide conservation advice, indicating a high interest in the scientific community for relating results to practical management. 4. Populations in MPAs do not differ genetically from populations outside MPAs, indicating that MPAs in the Baltic Sea do not protect genetic diversity specifically, but that populations in MPAs are a representative subset of populations in the Baltic Sea. 5. Recommendations are provided for cases where genetic information is available but not used in management, particularly for non‐commercial species with important ecosystem function. 6. Improved channels for effective communication between academia and practical management on Baltic Sea genetic biodiversity are needed. A web page that can be used for knowledge transfer is highlighted here.publishedVersio

Does your organization have an unhealthy identity?

Issue of study: The Swedish dairy company Vattnadahl is currently going through extensive changes, battling new market demands and internal reorganizations. As a consequence, the organization is facing challenges related to its organizational identity. From a theoretical perspective, organizational identity consists of an internal and an external part that together dynamically construct the identity. In case of an unbalance between the internal and the external part, there is a risk of impairing the organizational health. This effect is not, however, further investigated in existing theory. Purpose: The main purpose of this study is to gain insights into how a temporary disassociation between the internal and the external definition of organizational identity is affecting organizational health. Further, the sub-purpose is to illustrate Vattnadahl in the light of identity dynamics and from this investigate if those with power within an organization have greater influence of the identity balance. Methodology: This study was conducted from a qualitative and inductive approach and was performed as a case study at Vattnadahl. From this, collection and compilation of empirical data at Vattnadahl initiated the study. Subsequently, a literature study was conducted in order to explain the phenomena found at Vattnadahl. Finally, the case company was analyzed from an analytical framework developed by the authors. Conclusions: Summarizing the study, it can be concluded that Vattnadahl has an unbalanced identity strongly influenced by their external image. Consequently, the organization is experiencing the dysfunction of hyper-adaptation, which is affecting their organizational health. This effect can be compiled into six unhealthiness factors; stress, frustration, confusion, lack of pride, anxiety, and lack of initiative. Furthermore, it can be concluded that those with power within Vattnadahl have a greater influence on the identity balance compared to other employees. The thesis also provides a development of the construction of possible dysfunctions occurring from an unbalanced identity, by questioning the existing definitions and nuancing the concepts. The nuancing of the concepts is divided into two perspectives; a stakeholder perspective and a nuanced grading perspective. The stakeholder perspective implies that the dysfunction could differ depending on which stakeholder that is in focus of the analysis. The nuancing grading perspective indicates a possibility for dysfunctions to simultaneously exist, but in different strengths, such as softer or stronger

Drying aqueous colloidal systems: Molecular interactions, self-assembly and homeostatic behavior

Evaporation is a ubiquitous process in aqueous systems, which may be advantageous for processing materials through drying or deadly for living systems. Since surfactants, polymers and particles are usually non-volatile, water evaporation will lead to the build-up of concentration gradients in the system, from the air/liquid interface into the dispersion’s bulk. These concentration gradients will in turn generate structuration gradients in the colloidal system, which lead to changes in transport properties along the gradients. We will show that such a feedback loop on water evaporation can lead to non-linear behaviors, which are crucial for land-living animals’ survival and opens new avenues in drying and filtration processes. We designed millifluidic drying cells, which consist of a small capillary attached to a large reservoir, with one tip exposed to air at a controlled relative humidity. Chemical potential boundary conditions are thus set and controlled during drying. We monitored drying with time with a combination of mapping techniques: polarized microscopy, infra-red microscopy and coherent small-angle scattering, which yields both concentration and structuration gradients. We also measured independently the evaporation rate through gravimetry. Using simple surfactant aqueous solutions, we show that the evaporation rate is nearly independent of water evaporation driving force, the air relative humidity [1]. Strikingly, this behavior is identical to that of stratum corneum, skin’s outer layer. We demonstrate that this non-linear behavior stems from the feedback loop on water transport. Dryer air should lead to a higher evaporation rate due to an increased chemical potential difference between the air and the solution. However, this variation is absorbed in a very thin and dry phase at the air/water interface. This phase corresponds to dramatically low water diffusion coefficients, which in turn efficiently decrease water evaporation [2]. Uncovering the mechanism of this homeostatic behavior opens new strategies to evaluate the impact of a formulation on skin, lung or tear films. We will also show that this mechanism becomes relevant when drying, or filtering, dispersions of interpenetrable colloids, such as microgels or “hairy” particles [3]. Indeed, large changes in water chemical potential and permeabilities will occur in the concentrated regime, in contrast to the drying of more conventional colloidal dispersions. Taking these molecular interactions into account is crucial for the processing of more complex, and thus realistic, colloidal dispersions into materials. Please click Additional Files below to see the full abstract

Counterions at charge-modulated substrates

We consider counterions in the presence of a single planar surface with a spatially inhomogeneous charge distribution using Monte-Carlo simulations and strong-coupling theory. For high surface charges, multivalent counterions, or pronounced substrate charge modulation the counterions are laterally correlated with the surface charges and their density profile deviates strongly from the limit of a smeared-out substrate charge distribution, in particular exhibiting a much increased laterally averaged density at the surface.Comment: 7 page

The extended MHC haplotypes and their role in sarcoidosis

A large part of the genomic arrangement regulating the immune system is located in the Major Histocompatibility Complex (MHC) region on chromosome 6p21.31. Human leucocyte antigen (HLA) genes, which encode the antigen presenting molecules, are located in MHC class I and II, while the MHC class III region contains non-HLA genes, e.g. butyrophilin-like protein 2 (BTNL2), tumor necrosis factor (TNF) and complement C4. Most genes in the MHC region play an important role in susceptibility to autoimmune and infectious diseases. Sarcoidosis is a complex granulomatous disorder with varying a clinical presentation. A multitude of studies have reported strong associations between genes in the MHC and sarcoidosis. The structure of the MHC is characterized by a high degree of polymorphism, due to population-specific and highly conserved extended haplotypes, leading to a complicated pattern of linkage disequilibrium (LD). This makes dissecting disease associations within individual MHC genes difficult. The primary aims of this Study were to study the overall polymorphism of the MHC region in Finnish subjects, to investigate MHC as a susceptibility locus for sarcoidosis and to find predictive markers for the prognosis of the disease. In Study I, extended MHC haplotypes covering genes within MHC class I (HLA-A, -B), MHC class II (HLA-DRB1, -DQB1 and DPB1) and MHC class III (e.g. TNF and BTNL2) were constructed and LD between the genes studied in a Finnish population sample. We discovered that the extended MHC haplotypes could be grouped, based on a similar functional variant (e.g. truncating protein) or a similar structure of the peptide binding site. In Study II, we replicated a previously reported HLA-DRB1*03:01 association with a favourable prognosis of sarcoidosis in Finland (P=0.007, OR=2.7). Using the extended MHC haplotype approach, we detected novel and independent variants associated with sarcoidosis (HLA-DPB1*04:02; P=0.003, OR=0.48) or the disease course of sarcoidosis (HLA-DRB1*04:01-DPB1*04:01; P=0.02, OR=3.07). In Study IV, we explored four genes in the MHC class III region (LTA, TNF, AGER, BTNL2) and HLA-DRA, and performed a replication and meta-analysis in four European populations. After adjusting for sex, population stratification and HLA-DRB1 alleles, four SNPs in the HLA- DRA/BTNL2 region were associated with non-Löfgren sarcoidosis; the strongest signal association was detected with rs3177928 (1.79x10-7, OR=1.90). In this Study, we also addressed guidelines for disease association studies dealing with immunogenetic data. The results of the extended MHC haplotype analysis discovered a unique haplotype admixture in the Finnish population, which may have implications to MHC-related disease associations. Our sarcoidosis study provided new insights to predicting the disease prognosis, with different distributions of MHC variants associating different patterns of progression, further promoting the importance of MHC region in sarcoidosis predisposition. Especially, the region covering the genes BTNL2 and HLA-DRA warrants further studies in larger samples and in different ethnic groups. To conclude, this Study showed the importance of studying extended MHC haplotypes in well-characterized samples, in order to understand the complex MHC structure and to distinguish variants associations with the trait.Sarkoidoosi on useita elimiä samanaikaisesti vaurioittava tulehdussairaus, jonka aiheuttajaa ei tunneta. Sarkoidoosissa eri elimiin muodostuu pieniä tulehdussolukertymiä eli granuloomia, varsinkin keuhkoihin ja imusolmukkeisiin. Suomessa sarkoidoosiin sairastuu vuosittain noin 500 henkilöä. Sarkoidoosin taudinkuva on vaihteleva, yleisoireena on tyypillisesti yskää, kohtalaista kuumeilua ja väsymystä. Suurin osa tautiin sairastuneista ei tarvitse hoitoa, koska lieväoireinen tauti paranee monesti itsestään. 20%:lla tauti kuitenkin kroonistuu jolloin keuhkofibroosin ohella voi löytyä muutoksia ihossa, silmissä, maksassa/pernassa, luustossa, sydänlihaksessa, keskushermostossa jne. Nykykäsityksen mukaan sarkoidoosin syntymisen taustalla ovat sekä ympäristötekijät että geenit, joista tärkeimpinä pidetään MHC-alueen geenejä, kuten HLA-DRB1 ja BTNL2. MHC-alue kromosomissa 6 (6p21.3, Major Histocompatibility Complex) sisältää joukon geenejä, joista suurin osa liittyy ihmisen immuunivasteen muodostumiseen ja säätelyyn. MHC-alue jakaantuu kolmeen luokkaan. Elinsiirtojen kudossopeutuvuutta määrittelevät klassiset transplantaatiogeenit, HLA-A, -B, -DRB1, -DQB1 ja -DPB1, kuuluvat joko luokkaan I tai II. Näiden HLA-geenien päätehtävä on esitellä peptidejä (antigeenejä) immuunijärjestelmälle. Luokan III alueella on geenejä, kuten esimerkiksi C4 komplementtigeenit ja BTNL2, jotka liittyvät mm. tulehdusreaktion syntyyn sekä solujen väliseen viestintään. Tämän väitöskirjatyön tarkoituksena oli kartoittaa, miten suomalaisten MHC-alueen geenit jakaantuvat ja esiintyvät yhdessä, ja käyttää näitä tietoja hyväksi tutkiessa MHC geenien merkitystä sarkoidoosin alttiuteen ja ennusteeseen. I. osajulkaisussa tutkimme erilaisten MHC-geenikombinaatioiden (haplotyyppien) jakaumia ja geenien välistä kytkeytymistä (kytkentäepätasapainoa). Totesimme, että MHC-haplotyyppejä voi ryhmitellä sen mukaan miten ne sisältävät samoja toiminnallisia geenimuotoja (esim. C4 geenin puutos) tai samankaltaisia antigeenin sitoutumiskohtia. Tutkimustuloksemme osoittivat, että usean MHC-geenin samanaikainen analysointi ja haplotyyppirakenteiden tunteminen voi auttaa ehdokasgeenien paikantamisessa. Osajulkaisuissa II ja III toistimme aiemmin muista väestöistä löydettyjen geenien, HLA-DRB1*03:01 and BTNL2, yhteyden sarkoidoosin ennusteen myös suomalaisessa väestössä. Tutkimuksissamme löysimme myös uusia sarkoidoosille altistavia (HLA-DRB1*04:01-DPB1*04:01) ja siltä suojaavia (HLA-DPB1*04:02) geenejä. IV osajulkaisussa monikansallinen otos vahvisti sarkoidoosiin liittyvien MHC luokan II ja III ehdokasgeenien ja niissä löytyneiden geenimuotojen merkityksen taudin alttiudelle. Sarkoidoosille altistavan geenin osoittaminen on MHC-alueella haastavaa, koska alueen geenit ovat tiukasti kytkeytyneet toisiinsa, ja ehdokasgeenit voivat vaihdella eri väestöjen välillä. Tässä väitöskirjatyössä osoitimme, että MHC-alueen kokonaisvaltaisesta tutkimisesta on etua alttiusgeenien paikantamisessa. Hyödyntäen tätä lähestymistapaa - tutkimalla useita MHC-geenejä samanaikaisesti- löysimme MHC-geenialueelta uusia sarkoidoosiin ja sarkoidoosin ennusteeseen liittyviä geenimuotoja. Ne auttavat ymmärtämään sarkoidoosin monimuotoista geneettistä taustaa ja osoittavat MHC-geenien merkityksen sarkoidoosin alttiudelle. Jotta MHC-alueen geenejä voidaan käyttää ennustamaan suomalaisten sarkoidoosipotilaiden taudinkuvaa, tulee tulokset toistaa isommassa otoksessa

How Small Polar Molecules Protect Membrane Systems against Osmotic Stress: The Urea−Water−Phospholipid System

We investigate how a small polar molecule, urea, can act to protect a phospholipid bilayer system against osmotic stress. Osmotic stress can be caused by a dry environment, by freezing, or by exposure to aqueous systems with high osmotic pressure due to solutes like in saline water. A large number of organisms regularly experience osmotic stress, and it is a common response to produce small polar molecules intracellularly. We have selected a ternary system of urea-water-dimyristoyl phosphatidylcholine (DMPC) as a model to investigate the molecular mechanism behind this protective effect, in this case, of urea, and we put special emphasis on the applications of urea in skin care products. Using differential scanning calorimetry, X-ray diffraction, and sorption microbalance measurements, we studied the phase behavior of lipid systems exposed to an excess of solvent of varying compositions, as well as lipid systems exposed to water at reduced relative humidities. From this, we have arrived at a rather detailed thermodynamic characterization. The basic findings are as follows: (i) In excess solvent, the thermally induced lipid phase transitions are only marginally dependent on the urea content, with the exception being that the P phase is not observed in the presence of urea. (ii) For lipid systems with limited access to solvent, the phase behavior is basically determined by the amount (volume) of solvent irrespective of the urea content. (iii) The presence of urea has the effect of retaining the liquid crystalline phase at relative humidities down to 64% (at 27 °C), whereas, in the absence of urea, the transition to the gel phase occurs already at a relative humidity of 94%. This demonstrates the protective effect of urea against osmotic stress. (iv) In skin care products, urea is referred to as a moisturizer, which we find slightly misleading as it replaces the water while keeping the physical properties unaltered. (v) In other systems, urea is known to weaken the hydrophobic interactions, while for the lipid system we find few signs of this loosening of the strong segregation into polar and apolar regions on addition of ure