Declining invasive and rising in situ melanoma incidence trends in Iceland: A nationwide cohort study.

BACKGROUND: Melanoma is increasing worldwide, with incidence rates of invasive melanoma and melanoma in situ (MIS) varying by country. OBJECTIVE: To provide updated invasive melanoma and MIS incidence and mortality trends in Iceland and explore differences among sex and rurality. METHODS: In this whole-population study using the Icelandic Cancer Registry, patients diagnosed with invasive melanoma or MIS between 1957 and 2021 were included. Sex-specific world standardized incidence (WSR) and mortality rates were assessed by rurality. Joinpoint analysis was used to calculate trends using annual per cent change (APC). RESULTS: Invasive melanoma incidence rates increased from 0.66 to 7.0 (men) and 1.6 to 11.0 (women) per 100,000 person-years, and from 0.2 to 4.0 and 0.9 to 9.5 per 100,000 person-years for MIS in men and women, respectively, with a statistically significant linear trend (p = 0.001). WSR peaked in both men and women (10.7, 17.9 per 100,000 person-years) between 2002 and 2006 and has since been trending down. Between 1991 and 2005, the rise in invasive melanoma occurred more frequently in urban regions. Between 2003 and 2005, joinpoint analysis demonstrated a downtrend in invasive melanoma in men and women (-0.29, -0.73; p < 0.05). For MIS, the WSR peaked at 12.4 per 100,000 person-years in women between 1997 and 2001 before down-trending to 4.2. In recent years (2017-2021), the WSR has been steadily increasing in women with an APC of 1.43. Melanoma-specific mortality has decreased since 2012 (-0.07; p < 0.05). CONCLUSIONS: Declining invasive melanoma incidence and mortality rates in conjunction with the recent rise in MIS may reflect the impact of Iceland's sun safety and anti-sunbed educational campaigns, federal regulation of sunbeds and earlier melanoma detection in urban areas.

Predesigned perovskite crystal waveguides for room-temperature exciton-polariton condensation and edge lasing.

Perovskite crystals-with their exceptional nonlinear optical properties, lasing and waveguiding capabilities-offer a promising platform for integrated photonic circuitry within the strong-coupling regime at room temperature. Here we demonstrate a versatile template-assisted method to efficiently fabricate large-scale waveguiding perovskite crystals of arbitrarily predefined geometry such as microwires, couplers and splitters. We non-resonantly stimulate a condensate of waveguided exciton-polaritons resulting in bright polariton lasing from the transverse interfaces and corners of our perovskite microstructures. Large blueshifts with excitation power and high mutual coherence between the different edge and corner lasing signals are detected in the far-field photoluminescence, implying that a spatially extended condensates of coherent polaritons has formed. The condensate polaritons are found to propagate over long distances in the wires from the excitation spot and can couple to neighbouring wires through large air gaps, making our platform promising for integrated polaritonic circuitry and on-chip optical devices with strong nonlinearities.

Dirac exciton-polariton condensates in photonic crystal gratings.

Bound states in the continuum have recently been utilized in photonic crystal gratings to achieve strong coupling and ultralow threshold condensation of exciton-polariton quasiparticles with atypical Dirac-like features in their dispersion relation. Here, we develop the single- and many-body theory of these new effective relativistic polaritonic modes and describe their mean-field condensation dynamics facilitated by the interplay between protection from the radiative continuum and negative-mass optical trapping. Our theory accounts for tunable grating parameters giving full control over the diffractive coupling properties between guided polaritons and the radiative continuum, unexplored for polariton condensates. In particular, we discover stable cyclical condensate solutions mimicking a driven-dissipative analog of the zitterbewegung effect characterized by coherent superposition of ballistic and trapped polariton waves. We clarify important distinctions between the polariton nearfield and farfield explaining recent experiments on the emission characteristics of these long lived nonlinear Dirac polaritons.

Antiferromagnetic Ising model in a triangular vortex lattice of quantum fluids of light.

Vortices are topologically distinctive objects appearing as phase twists in coherent fields of optical beams and Bose-Einstein condensates. Structured networks and artificial lattices of coupled vortices could offer a powerful platform to study and simulate interaction mechanisms between constituents of condensed matter systems, such as antiferromagnetic interactions, by replacement of spin angular momentum with orbital angular momentum. Here, we realize such a platform using a macroscopic quantum fluid of light based on exciton-polariton condensates. We imprint all-optical hexagonal lattice that results into a triangular vortex lattice, with each cell having a vortex of charge l = ±1. We reveal that pairs of coupled condensates spontaneously arrange their orbital angular momentum antiparallel, implying a form of artificial orbital "antiferromagnetism." We discover that correlation exists between the emergent vortex patterns in triangular condensate lattices and the low-energy solutions of the corresponding antiferromagnetic Ising system. Our study offers a path toward spontaneously ordered vortex arrays with nearly arbitrary configurations and controlled couplings.

[Migration of an intrauterine contraceptive device outside of the uterine cavity - a case report].

Intrauterine devices (IUDs) are a safe and common form of contraception. Uterine rupture and migration of the IUD is a rare complication of insertion but can be serious and cause damage to adjacent organs. We present a case report of a 43 year old woman with chronic abdominal pain who was diagnosed with an IUD in the wall of the sigmoid colon. That IUD had been inserted in the uterine cavity 22 years earlier.

Quantum vortex formation in the "rotating bucket" experiment with polariton condensates.

The appearance of quantized vortices in the classical "rotating bucket" experiments of liquid helium and ultracold dilute gases provides the means for fundamental and comparative studies of different superfluids. Here, we realize the rotating bucket experiment for optically trapped quantum fluid of light based on exciton-polariton Bose-Einstein condensate in semiconductor microcavity. We use the beating note of two frequency-stabilized single-mode lasers to generate an asymmetric time-periodic rotating, nonresonant excitation profile that both injects and stirs the condensate through its interaction with a background exciton reservoir. The pump-induced external rotation of the condensate results in the appearance of a corotating quantized vortex. We investigate the rotation frequency dependence and reveal the range of stirring frequencies (from 1 to 4 GHz) that favors quantized vortex formation. We describe the phenomenology using the generalized Gross-Pitaevskii equation. Our results enable the study of polariton superfluidity on a par with other superfluids, as well as deterministic, all-optical control over structured nonlinear light.

Electrically tunable Berry curvature and strong light-matter coupling in liquid crystal microcavities with 2D perovskite.

The field of spinoptronics is underpinned by good control over photonic spin-orbit coupling in devices that have strong optical nonlinearities. Such devices might hold the key to a new era of optoelectronics where momentum and polarization degrees of freedom of light are interwoven and interfaced with electronics. However, manipulating photons through electrical means is a daunting task given their charge neutrality. In this work, we present electrically tunable microcavity exciton-polariton resonances in a Rashba-Dresselhaus spin-orbit coupling field. We show that different spin-orbit coupling fields and the reduced cavity symmetry lead to tunable formation of the Berry curvature, the hallmark of quantum geometrical effects. For this, we have implemented an architecture of a photonic structure with a two-dimensional perovskite layer incorporated into a microcavity filled with nematic liquid crystal. Our work interfaces spinoptronic devices with electronics by combining electrical control over both the strong light-matter coupling conditions and artificial gauge fields.

Spontaneous Formation of Time-Periodic Vortex Cluster in Nonlinear Fluids of Light.

We demonstrate spontaneous formation of a nonlinear vortex cluster state in a microcavity exciton-polariton condensate with time-periodic sign flipping of its topological charges at the GHz scale. When optically pumped with a ring-shaped nonresonant laser, the trapped condensate experiences intricate high-order mode competition and fractures into two distinct trap levels. The resulting mode interference leads to robust condensate density beatings with periodic appearance of orderly arranged phase singularities. Our work opens new perspectives on creating structured free-evolving light, and singular optics in the strong light-matter coupling regime.

Realizing Optical Persistent Spin Helix and Stern-Gerlach Deflection in an Anisotropic Liquid Crystal Microcavity.

Spin-orbit interactions which couple the spin of a particle with its momentum degrees of freedom lie at the center of spintronic applications. Of special interest in semiconductor physics are Rashba and Dresselhaus spin-orbit coupling. When equal in strength, the Rashba and Dresselhaus fields result in SU(2) spin rotation symmetry and emergence of the persistent spin helix only investigated for charge carriers in semiconductor quantum wells. Recently, a synthetic Rashba-Dresselhaus Hamiltonian was shown to describe cavity photons confined in a microcavity filled with optically anisotropic liquid crystal. In this Letter, we present a purely optical realization of two types of spin patterns corresponding to the persistent spin helix and the Stern-Gerlach experiment in such a cavity. We show how the symmetry of the Hamiltonian results in spatial oscillations of the spin orientation of photons traveling in the plane of the cavity.

Geometric frustration in polygons of polariton condensates creating vortices of varying topological charge.

Vorticity is a key ingredient to a broad variety of fluid phenomena, and its quantised version is considered to be the hallmark of superfluidity. Circulating flows that correspond to vortices of a large topological charge, termed giant vortices, are notoriously difficult to realise and even when externally imprinted, they are unstable, breaking into many vortices of a single charge. In spite of many theoretical proposals on the formation and stabilisation of giant vortices in ultra-cold atomic Bose-Einstein condensates and other superfluid systems, their experimental realisation remains elusive. Polariton condensates stand out from other superfluid systems due to their particularly strong interparticle interactions combined with their non-equilibrium nature, and as such provide an alternative testbed for the study of vortices. Here, we non-resonantly excite an odd number of polariton condensates at the vertices of a regular polygon and we observe the formation of a stable discrete vortex state with a large topological charge as a consequence of antibonding frustration between nearest neighbouring condensates.

[Stenting for colorectal cancer obstruction in Icelandic patients].

INTRODUCTION: Self-expandable metal stents (SEMS) are a known treatment option for obstruction due to colorectal cancer. The objective of this project was to estimate the usage of such stents in Iceland between 2000-2018. We evaluated the number of patients who received the stent as a bridge to surgery (BtoS) or as a palliative therapy (PT) and evaluated complication rate and the technical and clinical success rate. MATERIAL AND METHODS: Retrospective review of patients in Landspitali University Hospital who received SEMS for malignant colorectal obstruction. Search was conducted using diagnostic and theraputic codes in the Icelandic electronic medical record system. RESULTS: A total of 43 patients with colorectal cancer received in total 53 SEMS for obstruction, the first patient in 2005. More patient received SEMS as PT (n=27) than as BtoS (n=16). Colon perforation occurred in 5 patients (12%). A resection with primary anastomosis was performed in 69% of the BtoS patients. The majority of the PT patients did not receive an operation (63%). Permanent stoma ratio was 27% for BtoS patients and 22% for PT patients. CONCLUSION: SEMS served as BtoS with resection and primary anastomosis for the majority of patients in the BtoS group. For a majority of patients in the PT group, SEMS could be used to avoid surgery. The perforation rate was relatively high. Information on techincal and clinical success was poorly recorded. Because of the retrospective nature of the study and the small population size all results should be interpreted with caution.

Amplification of nonlinear polariton pulses in waveguides.

Using a sub-millimeter exciton-polariton waveguide suitable for integrated photonics, we experimentally demonstrate nonlinear modulation of pico-Joule pulses at the same time as amplification sufficient to compensate the system losses. By comparison with a numerical model we explain the observed interplay of gain and nonlinearity as amplification of the interacting polariton field by stimulated scattering from an incoherent continuous-wave reservoir that is depleted by the pulses. This combination of gain and giant ultrafast nonlinearity operating on picosecond pulses has the potential to open up new directions in low-power all-optical information processing and nonlinear photonic simulation of conservative and driven-dissipative systems.

The Scandinavian Sarcoma Group Central Register: 6,000 patients after 25 years of monitoring of referral and treatment of extremity and trunk wall soft-tissue sarcoma.

Purpose - We wanted to examine the potential of the Scandinavian Sarcoma Group (SSG) Central Register, and evaluate referral and treatment practice for soft-tissue sarcomas in the extremities and trunk wall (STS) in the Nordic countries. Background - Based on incidence rates from the literature, 8,150 (7,000-9,300) cases of STS of the extremity and trunk wall should have been diagnosed in Norway, Finland, Iceland, and Sweden from 1987 through 2011. The SSG Register has 6,027 cases registered from this period, with 5,837 having complete registration of key variables. 10 centers have been reporting to the Register. The 5 centers that consistently report treat approximately 90% of the cases in their respective regions. The remaining centers have reported all the patients who were treated during certain time periods, but not for the entire 25-year period. Results - 59% of patients were referred to a sarcoma center untouched, i.e. before any attempt at open biopsy. There was an improvement from 52% during the first 5 years to 70% during the last 5 years. 50% had wide or better margins at surgery. Wide margins are now achieved less often than 20 years ago, in parallel with an increase in the use of radiotherapy. For the centers that consistently report, 97% of surviving patients are followed for more than 4 years. Metastasis-free survival (MFS) increased from 67% to 73% during the 25-year period. Interpretation - The Register is considered to be representative of extremity and trunk wall sarcoma disease in the population of Scandinavia, treated at the reporting centers. There were no clinically significant differences in treatment results at these centers.

Oestrogen receptor status, treatment and breast cancer prognosis in Icelandic BRCA2 mutation carriers.

BACKGROUND: The impact of an inherited BRCA2 mutation on the prognosis of women with breast cancer has not been well documented. We studied the effects of oestrogen receptor (ER) status, other prognostic factors and treatments on survival in a large cohort of BRCA2 mutation carriers. METHODS: We identified 285 breast cancer patients with a 999del5 BRCA2 mutation and matched them with 570 non-carrier patients. Clinical information was abstracted from patient charts and pathology records and supplemented by evaluation of tumour grade and ER status using archived tissue specimens. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival using Cox regression. The effects of various therapies were studied in patients treated from 1980 to 2012. RESULTS: Among mutation carriers, positive ER status was associated with higher risk of death than negative ER status (HR=1.94; 95% CI=1.22-3.07, P=0.005). The reverse association was seen for non-carriers (HR=0.71; 95% CI: 0.51-0.97; P=0.03). CONCLUSIONS: Among BRCA2 carriers, ER-positive status is an adverse prognostic factor. BRCA2 carrier status should be known at the time when treatment decisions are made.

Tumour diploidy and survival in breast cancer patients with BRCA2 mutations.

It is not well known to what extent carrying a BRCA2 mutation affects the survival of women with breast cancer and prognostic factors among BRCA2-positive women warrant investigation. Using a record linkage approach we compared the long-term survival in carriers and noncarriers of an inherited BRCA2 founder mutation (999del5), and sought to identify prognostic factors among the BRCA2 mutation-positive subset, including markers of genetic instability (aneuploidy) and mitotic activity (S-phase fraction). We established the genetic status of 2,967 Icelandic breast cancer patients (215 mutation carriers and 2,752 noncarriers) diagnosed from 1955 to 2004, representing 72 % of all cases diagnosed in the country during this period. Tumour ploidy and S-phase fraction were assessed on tumour cells by DNA flow cytometry. Prognostic factors were assessed blindly with respect to mutation status. Univariate and multivariate hazard ratios (HR) were estimated for breast cancer-specific survival by BRCA2 status, using Cox regression. After a median follow-up of 9.5 years, BRCA2 mutation carriers had a higher risk of death from breast cancer than noncarriers (HR 1.64, 95 % CI 1.24-2.16, p < 0.001). The risk increase was restricted to women with diploid tumours (HR 3.03, 95 % CI 1.91-4.79, p < 0.001). Among breast cancer patients with aneuploid tumours, survival of carriers was similar to that of noncarriers (HR 0.76, 95 % CI 0.41-1.41, p = 0.38). Increased tumour size and a positive nodal status predicted worse prognosis in all patients, whereas the highly correlated prognostic factors diploidy, low proliferative activity and a positive estrogen receptor status had reverse effects in mutation carriers and noncarriers. Breast cancer patients who carry the Icelandic founder BRCA2 mutation have inferior long-term survival than noncarriers, but the adverse prognosis is restricted to mutation carriers with diploid, slowly proliferating tumours.

Laparostomy management using the ABThera™ open abdomen negative pressure therapy system in a grade IV open abdomen secondary to acute pancreatitis.

Wound control in laparostomy for the treatment of intra-abdominal hypertension remains challenging and numerous techniques have been described. We report the first UK experience with a new commercially available device specifically designed to facilitate management of the open abdomen. A 44-year-old gentleman presented with a 3-day history of constant severe epigastric pain and associated vomiting. Amylase was markedly elevated and he was admitted for supportive management of pancreatitis, with subsequent transfer to intensive care due to severe systemic inflammatory syndrome. The patient decompensated, developing intra-abdominal hypertension with renal and respiratory failure. This was successfully managed by performing a laparostomy and using an ABThera™ Open Abdomen Negative Pressure Therapy System (KCI, San Antonio, TX). We describe its use to facilitate wound control, including enteroatmospheric fistula, allowing granulation and eventual restoration of gastrointestinal continuity 383-days after admission. We found the ABThera™ System proved to be a useful treatment adjunct, protecting intra-abdominal contents while removing large volumes of exudate and infected material from within the abdominal cavity. Complex cases such as this remain infrequent and this article provides a summary of our experience, including a review of indications for laparostomy and the underlying basic science in this difficult area.

[Clostridium difficile infections at Landspítali - 1998-2008]. / Clostridium difficile sýkingar á Landspítala 1998-2008.

OBJECTIVE: To study the epidemiology and severity of C. difficile infections (CDI) at Landspítali over 11 year period, 1998-2008. MATERIAL AND METHODS: CDI were identified by a positive toxin assay in stools from the database of the Department of Microbiology. Chart review was conducted on patients diagnosed in January and June each year during the study period, a total of 237 infections. RESULTS: Overall, 1,861 of 11,968 submitted stool samples were positive for C. difficile toxin, representing 1,492 infections. The population-based incidence was 29% higher in the end than in the beginning of the period and was highest in the age group >80 years where it was 387 cases per 100,000 person-years. The incidence per 1,000 admissions and 10,000 hospital days increased by 71% and 102%, respectively. 47% of the infections were nosocomial. Most patients had history of antibiotic exposure prior to the infection and the most common symptom was diarrhea. Response to a single antibiotics course was good (93%). No patient required surgery due to colitis. CONCLUSION: The incidence of CDI was higher in 2008 than 11 years before. Most patients had well characterized risk factors for CDI. For most patients a single course of metronidazole treatment resolved the infection. Based on these data, the severity of CDI does not seem to be increasing in Iceland.

Ancestry-shift refinement mapping of the C6orf97-ESR1 breast cancer susceptibility locus.

We used an approach that we term ancestry-shift refinement mapping to investigate an association, originally discovered in a GWAS of a Chinese population, between rs2046210[T] and breast cancer susceptibility. The locus is on 6q25.1 in proximity to the C6orf97 and estrogen receptor alpha (ESR1) genes. We identified a panel of SNPs that are correlated with rs2046210 in Chinese, but not necessarily so in other ancestral populations, and genotyped them in breast cancer case:control samples of Asian, European, and African origin, a total of 10,176 cases and 13,286 controls. We found that rs2046210[T] does not confer substantial risk of breast cancer in Europeans and Africans (OR = 1.04, P = 0.099, and OR = 0.98, P = 0.77, respectively). Rather, in those ancestries, an association signal arises from a group of less common SNPs typified by rs9397435. The rs9397435[G] allele was found to confer risk of breast cancer in European (OR = 1.15, P = 1.2 x 10(-3)), African (OR = 1.35, P = 0.014), and Asian (OR = 1.23, P = 2.9 x 10(-4)) population samples. Combined over all ancestries, the OR was 1.19 (P = 3.9 x 10(-7)), was without significant heterogeneity between ancestries (P(het) = 0.36) and the SNP fully accounted for the association signal in each ancestry. Haplotypes bearing rs9397435[G] are well tagged by rs2046210[T] only in Asians. The rs9397435[G] allele showed associations with both estrogen receptor positive and estrogen receptor negative breast cancer. Using early-draft data from the 1,000 Genomes project, we found that the risk allele of a novel SNP (rs77275268), which is closely correlated with rs9397435, disrupts a partially methylated CpG sequence within a known CTCF binding site. These studies demonstrate that shifting the analysis among ancestral populations can provide valuable resolution in association mapping.

Parental origin of sequence variants associated with complex diseases.

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.