A trans-Neptunian object written transneptunian object, is any minor planet in the Solar System that orbits the Sun at a greater average distance than Neptune, which has a semi-major axis of 30.1 astronomical units. TNOs are further divided into the classical and resonant objects of the Kuiper belt, the scattered disc and detached objects with the sednoids being the most distant ones; as of October 2018, the catalog of minor planets contains 528 numbered and more than 2,000 unnumbered TNOs. The first trans-Neptunian object to be discovered was Pluto in 1930, it took until 1992 to discover a second trans-Neptunian object orbiting the Sun directly, 15760 Albion. The most massive TNO known is Eris, followed by Pluto, Haumea and Gonggong. More than 80 satellites have been discovered in orbit of trans-Neptunian objects. TNOs vary in color and are either grey-blue or red, they are thought to be composed of mixtures of rock, amorphous carbon and volatile ices such as water and methane, coated with tholins and other organic compounds.

Twelve minor planets with a semi-major axis greater than 150 AU and perihelion greater than 30 AU are known, which are called extreme trans-Neptunian objects. The orbit of each of the planets is affected by the gravitational influences of the other planets. Discrepancies in the early 1900s between the observed and expected orbits of Uranus and Neptune suggested that there were one or more additional planets beyond Neptune; the search for these led to the discovery of Pluto in February 1930, too small to explain the discrepancies. Revised estimates of Neptune's mass from the Voyager 2 flyby in 1989 showed that the problem was spurious. Pluto was easiest to find because it has the highest apparent magnitude of all known trans-Neptunian objects, it has a lower inclination to the ecliptic than most other large TNOs. After Pluto's discovery, American astronomer Clyde Tombaugh continued searching for some years for similar objects, but found none. For a long time, no one searched for other TNOs as it was believed that Pluto, which up to August 2006 was classified a planet, was the only major object beyond Neptune.

Only after the 1992 discovery of a second TNO, 15760 Albion, did systematic searches for further such objects begin. A broad strip of the sky around the ecliptic was photographed and digitally evaluated for moving objects. Hundreds of TNOs were found, with diameters in the range of 50 to 2,500 kilometers. Eris, the most massive TNO, was discovered in 2005, revisiting a long-running dispute within the scientific community over the classification of large TNOs, whether objects like Pluto can be considered planets. Pluto and Eris were classified as dwarf planets by the International Astronomical Union. In December 2018, the discovery of 2018 VG18, nicknamed "Farout", was announced. Farout is the most distant solar system object so-far observed and is about 120 AU away from the sun taking more than 1,000 years to complete one orbit. According to their distance from the Sun and their orbital parameters, TNOs are classified in two large groups: the Kuiper belt objects and the scattered disc objects.

The diagram to the right illustrates the distribution of known trans-Neptunian objects in relation to the orbits of the planets and the centaurs for reference. Different classes are represented in different colours. Resonant objects are plotted in classical Kuiper belt objects in blue; the scattered disc extends to the right, far beyond the diagram, with known objects at mean distances beyond 500 AU and aphelia beyond 1000 AU. The Edgeworth-Kuiper belt contains objects with an average distance to the Sun of 30 to about 55 AU having close-to-circular orbits with a small inclination from the ecliptic. Edgeworth-Kuiper belt objects are further classified into the resonant trans-Neptunian object, that are locked in an orbital resonance with Neptune, the classical Kuiper belt objects called "cubewanos", that have no such resonance, moving on circular orbits, unperturbed by Neptune. There are a large number of resonant subgroups, the largest being the twotinos and the plutinos, named after their most prominent member, Pluto.

Members of the classical Edgeworth-Kuiper belt include 50000 Quaoar and Makemake. The scattered disc contains objects farther from the Sun, with eccentric and inclined orbits; these orbits are non-planetary-orbit-crossing. A typical example is the most massive known Eris. Based on the Tisserand parameter relative to Neptune, the objects in the scattered disc can be further divided into the "typical" scattered disc objects with a TN of less than 3, into the detached objects with a TN greater than 3. In addition, detached objects have a time-averaged eccentricity greater than 0.2 The Sednoids are a further extreme sub-grouping of the detached objects with perihelia so distant that it is confirmed that their orbits cannot be explained by perturbations from the giant planets, nor by interaction with the galactic tides. Given the apparent magnitude of all but the biggest trans-Neptunian objects, the physical studies are limited to the following: thermal emissions for the largest objects colour indices, i.e. comparisons of the apparent magnitudes using different filters analysis of spectra and infraredStudying colours and spectra provides insight into the objects' origin and a potential correlation with other classes of objects, namely centaurs and some satellites of giant planets, suspected to originate in the Kuiper belt.

However, the inter

Gerrit Bolkestein was a Dutch politician and member of the Free-thinking Democratic League. Bolkestein was the Minister for Education and Science from 1939 until 1945, was part of the Dutch government-in-exile from 1940. In early 1944 he gave a radio address from London in which he said that after the war he would collect written evidence from Dutch people relating to the oppression they had endured during the Nazi occupation. Among those who heard the broadcast was Anne Frank, keeping a diary for two years, which she had spent multiple years in hiding, his comment that he was interested in diaries and letters, led Frank to edit what had been a diary kept for her own amusement. Frank died in Bergen-Belsen concentration camp, but her edited diary was saved, published in 1947. Bolkestein is the grandfather of prominent market liberal Frits Bolkestein, he is buried at Zorgvlied cemetery

Anaplastic large-cell lymphoma is a type of non-Hodgkin lymphoma involving aberrant T cells or null lymphocytes. It is described in detail in the "Classification of Tumours of the Haematopoietic and Lymphoid Tissues" edited by experts of the World Health Organisation; the term anaplastic large-cell lymphoma encompasses at least four different clinical entities, all sharing the same name, which histologically share the presence of large pleomorphic cells that express CD30 and T-cell markers. Two types of ALCL present as systemic disease and are considered as aggressive lymphomas, while two types present as localized disease and may progress locally. Anaplastic large cell lymphoma is associated with various types of medical implants; the clinical presentation varies according to the type of ALCL. Two of the ALCL subtypes are systemic lymphomas, in that they present with enlarged lymph nodes in multiple regions of the body, or with tumors outside the lymph nodes such as bone, muscle, liver, or spleen.

These 2 subtypes associate with weight loss and night sweats, can be lethal if left untreated without chemotherapy. The third type of ALCL is so-called cutaneous ALCL, is a tumor that presents in the skin as ulcers that may persist, or may involute spontaneously, recur; this type of ALCL manifests in different regions of the body and may extend to regional lymph nodes, i.e. an axillary lymph node if the ALCL presents in the arm. A rare subtype of ALCL has been identified in women; this is known as breast implant associated anaplastic large cell lymphoma, or BIA-ALCL. It can occur as a result of breast reconstruction after a diagnosis of breast cancer or as a result of cosmetic surgery using textured silicone implants. BIA-ALCL occurs in the fluid contained within the scar capsule surrounding the implant, rather than the breast tissue itself; the tumor manifests with swelling of the breast due to fluid accumulation around the implant. The disease may progress to invade the tissue surrounding the capsule, if left untreated may progress to the axillary lymph nodes.

It presents at a late stage and is associated with systemic symptoms. A form of ALCL is associated with implants. Textured breast implants are most identified and have been the focus of research, but tibial implants, dental implants, injection port implants, gluteal implants, gastric band placement have been reported. Risk is highest with most textured implants. Chronic inflammation is known to lead to lymphoma, it has been suggested that inflammation surrounding textured implants causes proliferation and activation of T-cells. The diagnosis of ALCL requires the examination by a pathologist of any enlarged lymph node, or any affected extranodal tissue where there the tumor is found, such as the intestine, the liver or bone in the case of systemic ALCL. For the case of cutaneous ALCL, a skin excision is recommended, for the diagnosis of ALCL associated with breast implants, a cytologic specimen of the effusion around the breast implant or complete examination of the breast capsule surrounding the implant is required.

Four forms of anaplastic large cell lymphoma are recognized: primary systemic anaplastic lymphoma kinase -positive ALCL, primary systemic ALK-negative ALCL, primary cutaneous ALCL, breast implant-associated ALCL. Anaplastic large cell lymphoma is characterized by "hallmark" cells and presence for CD30. Integration of this information with clinical presentation is crucial for final classification and management of patients; the classification acknowledges the recognition of large cells with pleomorphic nuclei and abundant cytoplasm. Required in the diagnosis is immunophenotypic evidence that cells are T lymphocytes, such as the expression of immunologic markers CD3 or CD4, but CD30 expression must be present in all neoplastic cells. Out of the 4 types of ALCL, one subtype of systemic ALCL expresses the protein anaplastic lymphoma kinase; the hallmark cells are of medium size and feature abundant cytoplasm, kidney shaped nuclei, a paranuclear eosinophilic region. Occasional cells may be identified in which the plane of section passes through the nucleus in such a way that it appears to enclose a region of cytoplasm within a ring.

On histological examination, hallmark cells must be present. Where they are not present in large numbers, they are located around blood vessels. Morphologic variants include the following types: Common Small-cell Lymphohistiocytic Sarcomatoid Signet ring The hallmark cells show immunopositivity for CD30. True positivity requires localisation of signal to the cell paranuclear region. Another useful marker which helps to differentiate this lesion from Hodgkin's lymphoma is clusterin; the neoplastic cells have a golgi staining pattern, characteristic of this lymphoma. The cells are typically positive for a subset of markers of T-cell lineage. However, as with other T-cell lymphomas, they are negative for the pan T-cell marker CD3. Cells are of null cell type; these lymphomas show immunopositivity for ALK protein in 70% of cases. They are typically positive for EMA. In contrast to many B-cell anaplastic CD30 positive lymphomas, they are negative for markers of Epstein–Barr virus. Greater than 90%