Physics-informed machine learning: case studies for weather and climate modelling.

Machine learning (ML) provides novel and powerful ways of accurately and efficiently recognizing complex patterns, emulating nonlinear dynamics, and predicting the spatio-temporal evolution of weather and climate processes. Off-the-shelf ML models, however, do not necessarily obey the fundamental governing laws of physical systems, nor do they generalize well to scenarios on which they have not been trained. We survey systematic approaches to incorporating physics and domain knowledge into ML models and distill these approaches into broad categories. Through 10 case studies, we show how these approaches have been used successfully for emulating, downscaling, and forecasting weather and climate processes. The accomplishments of these studies include greater physical consistency, reduced training time, improved data efficiency, and better generalization. Finally, we synthesize the lessons learned and identify scientific, diagnostic, computational, and resource challenges for developing truly robust and reliable physics-informed ML models for weather and climate processes. This article is part of the theme issue 'Machine learning for weather and climate modelling'.

Solitary intramedullary neurosarcoidosis: role of MRI in early detection.

BACKGROUND: Intramedullary neurosarcoidosis may be the first manifestation of the disease and may mimic a tumor clinically and radiographically. Two patients who presented with cervical intramedullary lesions on magnetic resonance imaging (MRI) scans were found to have neurosarcoidosis. CLINICAL PRESENTATION: Two patients with negative past medical history presented with progressive myelopathic features, and intramedullary cervical lesions were detected on MRI scan; the diagnosis was made on biopsy of the lesions. Early therapeutic intervention led to a favorable outcome. CONCLUSION: Intra-medullary neurosarcoidosis, especially in the cervical cord, can be the initial presentation of the disease, mimicking a tumor. MRI scan, biopsy, and, in fewer cases, angiotensin-converting enzyme levels can help with the diagnosis and may lead to a favorable outcome.

Cranial vault expansion: a comparison of magnetic coupled distraction to traditional surgical repositioning.

We compared the effectiveness of transcutaneously activated magnetic distraction of an osteotomized cranial bone flap to surgical repositioning of the flap with immediate, rigid internal fixation. Thirty immature rabbits were studied. All 30 rabbits underwent complete circumferential osteotomies of both parietal bones and postoperatively all were fitted with head frames. The rabbits were divided into 4 groups. The experimental magnetic distraction group consisted of 10 animals (group 1). In these rabbits magnets were secured to both parietal bones and magnets of opposite polarity were placed in the headframes. Each morning, the magnets in the head-frames were moved 0.25 mm farther away from the skull; this continued for 20 days for a total setback of 5 mm. Five animals served as the magnetic distraction controls; in these animals magnets were placed on the parietal bones but none were attached to the headframes (group 2). The experimental surgical repositioning group consisted of 10 rabbits (group 3). In each the parietal bones were elevated and fixed 5 mm above the rest of the skull using vitallium mesh and screws. Five rabbits made up the surgical respositioning control group (group 4). In these animals, parietal osteotomies were performed but the bones were secured to the skull in their original positions using hardware identical to that used in the experimental group. Six weeks later all of the animals were sacrificed. Two significant differences were identified between the experimental groups: (1) the cranial contours of the animals in the magnetic distraction group were rounded while those of the surgically repositioned group were acutely angled; (2) the osteotomies in rabbits in the magnetic distraction group were essentially completely ossified while in rabbits in the surgically repositioned group there were obvious gaps at the osteotomy sites that were filled with fibrous tissue. These conclusions support the potential utility of magnetically activated distraction as an alternative to current methods of cranial vault remodeling.

Transcriptional expression of tissue factor pathway inhibitor, thrombomodulin and von Willebrand factor in normal human tissues.

Under normal physiologic conditions, tissue factor pathway inhibitor (TFPI) is synthesized primarily by the microvascular endothelium. Using Northern blotting, we studied its transcriptional expression in different organs and compared it with the expression of two other endothelial specific proteins, namely thrombomodulin (TM) and von Willebrand factor (vWF). The order of mRNA expression for each protein was: TFPI-placenta>lung>liver>kidney>heart>skeletal muscle> or =pancreas>brain; TM-heart>pancreas>lung>skeletal muscle>kidney> or =liver>placenta>brain; and vWF-heart>skeletal muscle>pancreas>lung> or =kidney>placenta>brain>liver. Notably, heart expressed TM and vWF mRNA in large amounts and only small amounts of TFPI whereas lung expressed all three mRNAs in significant amounts. Placenta, on the contrary, expressed large amounts of TFPI but only small amounts of TM and vWF mRNAs. Brain by this technique was found to express undetectable amounts of TFPI and TM mRNAs but small amounts of vWF mRNA. The expression of TFPI mRNA in the brain was however detected by RT/PCR and the antigen was localized to the endothelium of microvessels as well as to the astrocytes and oligodendrocytes. Since ultimate expression of proteins is linked to the expression of their mRNAs, our data support a concept that vascular endothelium is made up of phenotypically diverse groups of cells and that endothelial cells of different vascular beds express specific sets of genes that enable them to carry out tissue-specific functions. Importantly, since astrocytes are known to express tissue factor, the TFPI expression by these cells may control coagulation in their microenvironment and their response to injury and inflammation.

Disseminated histoplasmosis and Wegener's granulomatosis.

Disseminated histoplasmosis is an unusual complication in endemic areas and has been reported in patients with an immunodeficient state, either from human immunodeficiency virus (HIV) infection or transplantation. In the non-HIV population, rare cases of disseminated histoplasmosis have been reported in patients with leukemia and Hodgkin's disease and patients receiving steroid therapy for various diseases. We report a case of disseminated histoplasmosis in a patient with Wegener's granulomatosis.

Cranial vault expansion using transcutaneously activated magnetic implants.

The technique of distraction osteogenesis has not been widely used in the treatment of problems of the head and face because of the need for external fixators. By using magnetic, rather than mechanical, forces to drive bone movement we hope to expand the applications of the technique to include the treatment of cranial vault deformities. Thirty immature rabbits were studied. Twenty-six of the rabbits underwent operations. Each of the 26 had 2 magnets fixed to its skull: one on the left parietal bone and one on the right parietal bone. Incomplete circumferential osteotomies were then performed around each magnet on 13 of the rabbits. A head frame was attached to each animal. Head frames without magnets were placed on 6 of the rabbits (3 with osteotomy, 3 without osteotomy) while 20 of the animals (10 with osteotomy, 10 without osteotomy) had 2 magnets mounted on the frames which were of opposite polarity to those implanted. The remaining 4 rabbits served as nonoperative controls. Six weeks later all of the animals were sacrificed. There were significant differences in the cranial volumes and contours between the groups of animals. Many of the differences were increased by coincident osteotomy. Associated histologic findings are described.

Kappa-opioid receptor binding varies inversely with tumor grade in human gliomas.

BACKGROUND: Opioid agonists can inhibit cell proliferation in various neural tumor cell lines, including rat gliomas. Because opioid antimitogenic effects are mediated by opioid receptors, it was of interest to the authors to determine opioid receptor levels in human brain tumors. METHODS: Specimens obtained at craniotomy from 30 patients with glioma and nonneoplastic brain disorders were evaluated for their kappa-opioid receptor binding. Kd and Bmax values were estimated from homologous competition binding curves with the kappa1-selective radioligand [3H]U69,593. RESULTS: Receptor binding density was greatest in nonneoplastic brain tissue, less in Grade 2 and 3 astrocytoma, and least in glioblastoma multiforme. CONCLUSIONS: These results suggest that opioid receptor-based stratification of grade may have clinical utility in distinguishing glioblastoma multiforme from lower grade astrocytomas, and thereby may facilitate diagnosis and treatment.

Development of a malignant peripheral nerve sheath tumor following treatment for testicular seminoma.

A novel case is reported in which an S2 nerve root malignant peripheral nerve sheath tumor was diagnosed approximately 8 years after treatment for Stage I testicular seminoma. This patient underwent right orchiectomy and subsequent irradiation therapy to the periaortic region, including the sacrum. Postoperative radiation therapy likely played a role in the development of this second malignancy.

Epidural hematoma producing Brown-Séquard syndrome: a case due to ruptured hemangioma with magnetic resonance imaging findings.

A man developed spontaneous spinal epidural hematoma secondary to ruptured hemangioma with a clinical picture resembling acute partial Brown-Séquard syndrome. Diagnosis by magnetic resonance imaging (MRI) allowed prompt surgical decompression and complete reversal of the neurological deficits. The diagnosis, etiology, and MRI findings of spinal epidural hematomas are discussed.

Primary Ki-1 (anaplastic large cell) lymphoma of the brain and spinal cord.

The authors report a case of primary Ki-1 lymphoma of the brain. The patient was a 4 1/2-year-old black girl who presented with a 4- and 5-day history of headaches, nausea, vomiting, neck stiffness, and difficulty in walking. Computed tomography (CT) scan of the brain showed two discrete densities in the left occipital lobe and in the brain stem. Magnetic resonance imaging (MRI) showed multiple densities scattered over the brain surface and brain stem. Microscopically, the tumor was an anaplastic neoplasm that diffusely infiltrated brain parenchyma. The neoplastic cells were large with amphophilic cytoplasm, large nuclei with irregular nuclear contours and prominent nucleoli. A high mitotic rate including atypical mitotic figures was noted. Immunohistochemical stains showed diffuse strong positivity for CD30 and moderate focal staining for epithelial membrane antigen. Leukocyte common antigen, cytokeratin, neuron specific enolase, monocyte/macrophage and B- and T-marker stains were negative. The histology was characteristic for Ki-1 large cell lymphoma. Cytologic examination of cerebrospinal fluid (CSF) demonstrated similar neoplastic cells. This is one of the first reports of this variant in the pediatric population.

Hyperdense basilar artery. An early computed tomography sign of thrombosis.

Noncontrast computed tomographic scans (CT scans) may show a hyperdense basilar artery before a brainstem infarct is visualized. This early sign should assist clinicians in confirming the diagnosis of basilar artery thrombosis. In a review of admission records of 750 patients with acute cerebrovascular disease from July 1991 to June 1993, at Saint Louis University Hospital, 20 patients were identified with clinical signs of nonlacunar, vertebrobasilar distribution infarction. Eight of these had pontomesencephalic ischemia. Their neuroimaging studies and medical records were evaluated. Four patients with acute clinical signs of pontomesencephalic infarction were found to have a hyperdense basilar artery on CT scans. The scans of 2 patients were excluded because of dolichoectasia; in the other 2 patients, the basilar artery appeared normal on the CT scan. The hyperdense basilar artery was detected within the early hours of neurological symptoms and often was the only detectable abnormality on the scan. In 3 patients extensive brainstem infarcts subsequently developed and they died. Basilar artery thrombosis was confirmed by pathological study in all these patients. In the fourth patient basilar artery occlusion and a large pontine infarct were evident by magnetic resonance imaging and angiography. A hyperdense basilar artery is a common feature on CT scans of patients presenting with an early clinical diagnosis of thrombosis. Untreated, the hyperintense basilar artery often portends a poor prognosis. Its ready recognition should guide further interventional studies and treatment.

Recurrent syncope and quadriplegia.

A 72-year-old man had posturally induced syncopal episodes, followed by quadriparesis, coma, and death. Neuroimaging studies supported the clinical diagnosis confirmed by neuropathological findings.

Unusual hemorrhage with use of synthetic dural substitute: MR findings.

Delayed hemorrhage is an unusual complication of silastic dural substitute that can have a prolonged latent period. Two such patients that presented 6 and 12 years following surgery and that were evaluated by MR imaging are reported.

Role of serotonin in hypothalamo pituitary adrenal axis escape from dexamethasone suppression.

1. The authors investigated the role of serotonin in the hypothalamo pituitary adrenal escape from depression. 2. Maximal dose of fenfluramine was administered to normal individuals pretreated with dexamethasone. 3. Fenfluramine had only a minimal and inconsistent effect on the hypothalamo pituitary adrenal axis in the presence of dexamethasone.

Fast feedback regulation of ACTH by cortisol.

1. Fast feedback regulation of ACTH by cortisol has not been well studied in humans. The authors studied the existence and characteristics of fast feedback regulation in normal humans. 2. Hydrocortisone hemisuccinate was infused at two different rates: 6 mg/hour and 12 mg/hour for two hours. 3. The studies did not demonstrate the existence of fast feedback regulation of basal ACTH concentration by cortisol in man. Further, the response was variable and the rate sensitive character was difficult to demonstrate.

Circadian rhythm of adrenergic regulation of adrenocorticotropin and cortisol secretion in man.

The effects of the alpha-adrenergic agonist methoxamine on the human hypothalamic-pituitary-adrenal axis was assessed by a placebo-controlled study in the morning and one in the evening. A 5-mg iv bolus dose of methoxamine in normal subjects caused a significant rise in plasma ACTH and cortisol concentrations in the morning study. However, no significant change in plasma cortisol or ACTH concentrations was noted during the evening study. These studies suggest the existence of a diurnal variation in alpha 1-adrenergic regulation of the hypothalamic-pituitary-adrenal axis.

Growth hormone response to growth hormone-releasing factor in depression.

A blunted growth hormone (GH) response to clonidine and other pharmacologic stimuli has been reported in patients with depression. This blunted growth hormone response to clonidine has led to the speculation that there is a central alpha-2 adrenergic receptor subsensitivity in depression. This hypothesis is based on the assumption that the pituitary somatotroph response to growth hormone-releasing factor (GHRF) is not altered in depression. In the present preliminary study, the somatotroph response to GHRF in depressed patients and normal controls has been evaluated in four depressed patients and four age- and sex-matched controls. The GH response to GRF is highly variable both in normal individuals and in the depressed patients studied. Larger numbers of patients and controls must be studied before any definitive conclusions can be drawn about GH responses to GRF in depressed patients.

Growth hormone-releasing factor stimulation test in depression.

The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.

What does the dexamethasone suppression test identify?

The authors studied the Dexamethasone Suppression Test (DST) in chronic pain patients with and without major depression, using items from a modified version of the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Montgomery-Asberg Depression Rating Scale. The purpose of the study was to identify the factor or factors which discriminated DST suppressors from nonsuppressors. The data suggest that depression and its profile are efficient discriminators of suppressors and nonsuppressors. Anxiety-related items were not as good as discriminators. The items that identified nonsuppression were the items that are often seen in combination in endogenous depression.