Achievement of Target Gain Larger than Unity in an Inertial Fusion Experiment.

On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.

AIMS: To test the reproducibility of the current World Health Organization (WHO) classification of thymic epithelial tumours and to determine the level of interobserver variation within a group of pathologists, all with experience and expertise in thoracic pathology. METHODS AND RESULTS: Ninety-five thymic tumours were circulated to a group of 17 pathologists in the UK and The Netherlands over a 1-year period. Participants were asked to classify them according to WHO criteria. The diagnoses were subjected to statistical analysis and kappa values calculated. The overall level of agreement was moderate (kappa 0.45). When the categories were reduced in number by creating two groups, (A + AB + B1 + B2 and B3 + C), the level of agreement increased to 0.62. An alternative grouping (A + AB + B1 and B2 + B3 + C) increased it slightly further. The best agreement was in tumour types A and AB. Difficulties arose in distinguishing B1 tumours from B2 tumours and B2 tumours from B3 tumours. CONCLUSIONS: Although the WHO system describes a number of well-defined tumour types with clear diagnostic criteria, the overall level of agreement was moderate and improved if some groups were amalgamated.

Segmental pulmonary veno-occlusive disease secondary to lung cancer.

This report describes two cases of segmental pulmonary vein occlusion secondary to lung malignancy in which lung biopsies showed histological features of veno-occlusive disease. These are the first cases to be reported in the literature in which such lung parenchymal histological changes are described in association with lung malignancy.

Inter-observer variation between pathologists in diffuse parenchymal lung disease.

BACKGROUND: There have been few inter-observer studies of diffuse parenchymal lung disease (DPLD), but the recent ATS/ERS consensus classification provides a basis for such a study. METHODS: A method for categorising numerically the percentage likelihood of these differential diagnoses was developed, and the diagnostic confidence of pathologists using this classification and the reproducibility of their diagnoses were assessed. RESULTS: The overall kappa coefficient of agreement for the first choice diagnosis was 0.38 (n = 133 biopsies), increasing to 0.43 for patients (n = 83) with multiple biopsies. Weighted kappa coefficients of agreement, quantifying the level of probability of individual diagnoses, were moderate to good (mean 0.58, range 0.40-0.75). However, in 18% of biopsy specimens the diagnosis was given with low confidence. Over 50% of inter-observer variation related to the diagnosis of non-specific interstitial pneumonia and, in particular, its distinction from usual interstitial pneumonia. CONCLUSION: These results show that the ATS/ERS classification can be applied reproducibly by pathologists who evaluate DPLD routinely, and support the practice of taking multiple biopsy specimens.

Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies.

AIM: The value of immunohistochemical staining in differentiating between malignant mesothelioma and pulmonary adenocarcinoma was re-examined using newly available commercial antibodies, with the aim of increasing the sensitivity and specificity of diagnosis, and simplifying the antibody panel required. METHODS: Forty one malignant mesotheliomas and 35 lung adenocarcinomas were studied. Commercial antibodies to calretinin, E-cadherin, N-cadherin, surfactant apoprotein A (SP-A), thyroid transcription factor 1 (TTF-1), thrombomodulin, and cytokeratin 5/6 were applied using the streptavidin-biotin-peroxidase complex procedure on formalin fixed, paraffin wax embedded tissue. RESULTS: E-cadherin was expressed in all adenocarcinomas and in 22% of the mesotheliomas. TTF-1 expression was detected in 69% of the adenocarcinomas and none of the mesotheliomas. Positive staining with polyclonal anticalretinin was detected in 80% of the mesotheliomas and 6% of the adenocarcinomas. N-cadherin was expressed in 78% of mesotheliomas and 26% of adenocarcinomas. Thrombomodulin was expressed in 6% of the adenocarcinomas and in 53% of the mesotheliomas. Cytokeratin 5/6 expression was detected in 6% of the adenocarcinomas and 63% of the mesotheliomas. The results were compared with the standard laboratory panel for mesothelioma diagnosis: anticarcinoembryonic antigen (anti-CEA), LeuM1, BerEP4, and HBME-1. CONCLUSION: Of the antibodies used in this study, E-cadherin was 100% sensitive for pulmonary adenocarcinoma and TTF-1 was 100% specific for pulmonary adenocarcinoma. The application of these two antibodies alone was adequate for the diagnosis of 69% of adenocarcinomas and 78% of mesotheliomas. Where TTF-1 is negative and E-cadherin is positive, a secondary panel of antibodies, including BerEP4 and LeuM1 (CD15) and antibodies directed against CEA, calretinin, cytokeratin 5/6, thrombomodulin, and N-cadherin, is required for differentiation between malignant mesothelioma and pulmonary adenocarcinoma.

The role and histological classification of needle core biopsy in comparison with fine needle aspiration cytology in the preoperative assessment of impalpable breast lesions.

AIMS: To investigate the role of needle core biopsy (NCB) in the preoperative assessment of impalpable breast lesions, mainly derived from the NHS Breast Screening Programme (NHSBSP) and to assess our own modifications to a suggested system for the classification of breast NCBs. METHODS: The NCB, fine needle aspiration cytology (FNAC), and radiology scores from 298 women with non-palpable breast lesions presenting between January 1997 and December 1998, together with the open biopsy results (where available) were collated and analysed. RESULTS: The mean follow up period was 15.8 months (range, 5-28). The 298 NCB specimens were categorised as follows: unsatisfactory/non-representative (B1; n = 61; 20.5%), benign but uncertain whether representative (B2r; n = 52; 17.4%), benign (B2; n = 103; 34.6%), lesions possibly associated with malignancy but essentially benign (B3a; n = 9; 3.0%), atypical epithelial proliferations (B3b; n = 10; 3.4%), suspicious of malignancy (B4; n = 7; 2.3%), and malignant (B5; n = 56; 18.7%). Excision biopsy was performed in 43 cases within the B1 (n = 19), B2r (n = 8), B2 (n = 8), and the B3a (n = 8; data unavailable in one case) categories, revealing malignancy in 18 (42.8%) cases and in 65 cases within the B3b, B4, and B5 categories, revealing malignancy in 64 cases (98.5%). The sensitivity of NCB for malignancy was 87.7%, with a specificity and positive predictive value of 99.3% and 98.5%, respectively. FNAC had an inadequacy rate of 58.7%, a complete sensitivity of 34.5% and a specificity of 47.6%. CONCLUSIONS: This study confirms the value of NCB in the preoperative assessment of impalpable breast lesions. Two new categories are suggested for the NCB classification; category B2r for benign breast tissue where representativeness is uncertain, and the subdivision of category B3 into B3a for benign lesions potentially associated with malignancy (for example, radial scars and intraduct papillomas) and B3b for more worrisome atypical epithelial proliferations. These will aid the accurate audit of NCB and identify more clearly the intellectual pathway leading to a particular assessment.

Non-invasive assessment of bleeding pulmonary artery aneurysms due to Behçet disease.

Because of its ability to depict intravascular, intramural, and extramural pathology, non-invasive imaging is well suited to assessing life-threatening hemoptysis that may complicate Behçet disease. We made exclusive use of CT angiography supplemented by MR to identify pulmonary thromboembolism, mediastinal lymphadenopathy, and bilateral pulmonary artery aneurysms with signs of previous unilateral rupture. Two-dimensional reformatted CT images provided surgeons with a road map of upstream and downstream vascular relationships prior to aneurysm resection. Imaging findings were confirmed by surgery and pathology. Non-invasive imaging proved to be a useful alternative to standard catheter arteriography in the preoperative assessment of hemoptysis in this patient with Behçet disease.

The distribution and density of airway vasoactive intestinal polypeptide (VIP) binding sites in cystic fibrosis and asthma.

The densities of airway binding sites for Vasoactive intestinal polypeptide (VIP) were determined using 125I-labelled VIP (IVIP) and the technique of autoradiography applied to cryostat sections. Tissue studied included: grossly normal airway tissue taken from lungs resected for bronchial carcinoma (Ca; n = 11) and lungs removed at transplant from patients with cystic fibrosis (CF; n = 7). Lung tissue obtained at post-mortem in cases of fatal asthma (n = 3) or lobes resected for bronchiectasis (n = 3) were taken as further disease controls. In the Ca controls there was dense IVIP labelling, of alveolar wall, blood vessels, airway epithelium, submucosal glands, and bronchial smooth muscle: labelling of bronchiolar smooth muscle was sparse. In comparison with the Ca controls, IVIP labelling of all tissue structures in CF, with the exception of bronchial smooth muscle, was reduced (P <0.01). The most striking reductions were associated with airway epithelium and alveolar wall. These reductions showed a similar trend in bronchiectasis but did not achieve statistical significance. There was no such change in lung tissue obtained from the cases of fatal asthma where labelling of bronchial smooth muscle and all other structures was similar to that of the Ca controls. It is likely that the reduction of VIP binding sites in CF is secondary to infection and inflammation.

Interstitial pneumonia in simian immunodeficiency virus infection.

Interstitial pneumonia unrelated to Pneumocystis carinii or other infections was observed histopathologically in 5 of 25 rhesus monkeys infected with simian immunodeficiency virus (SIV). The predominant lesion was lymphocytic infiltration of interalveolar septa and hyperplasia of peribronchial and perivascular lymphoid tissue. Immunohistochemical staining using a panel of antibodies against human T and B lymphocytes, macrophages, and immunoglobulins showed that peribronchial aggregates and interstitial infiltrates were predominantly B cells, whereas perivascular masses consisted mainly of T cells. One animal with a primary B-cell lymphoma of the spinal cord had secondary plasmacytoid lymphomatous nodules throughout the lung which were accompanied locally by reactive B-cell lymphoid follicles. Another animal also had large areas of diffuse alveolar fibrosis and epithelial metaplasia to a bronchiolar type. In two monkeys, branches of the pulmonary arteries showed intimal proliferation and organizing occlusive thrombi, some of which were mineralized.

Long-term survival of a patient with malignant lymphoma of bone.

Malignant lymphoma of bone is an uncommon tumour. A number of studies have outlined the clinicopathological findings and overall favourable prognosis in adults. We report on a woman whose tumour was originally diagnosed as a secondary carcinoma of the upper femur. Twenty-three years later following proximal femoral replacement, the original histology was reviewed using immunohistochemical techniques and revised to B-cell malignant lymphoma of bone.