Comprehensive assessment of cryogenic storage risk and quality management concerns: best practice guidelines for ART labs.

Recent publicized events of cryogenic storage tank failures have created nationwide concern among infertility patients and patients storing embryos and gametes for future use. To assure patient confidence, quality management (QM) plans applied by in vitro fertilization (IVF) laboratories need to include a more comprehensive focus on the cryostorage of reproductive specimens. The purpose of this review is to provide best practice guidelines for the cryogenic storage of sperm, oocytes, embryos, and other reproductive tissues (e.g., testicular and ovarian tissue, cord blood cells, and stem cells) and recommend a strategy of thorough and appropriate quality and risk management procedures aimed to alleviate or minimize the consequences from catastrophic events.

Dark Matter Search Results from the PICO-60 C_{3}F_{8} Bubble Chamber.

New results are reported from the operation of the PICO-60 dark matter detector, a bubble chamber filled with 52 kg of C_{3}F_{8} located in the SNOLAB underground laboratory. As in previous PICO bubble chambers, PICO-60 C_{3}F_{8} exhibits excellent electron recoil and alpha decay rejection, and the observed multiple-scattering neutron rate indicates a single-scatter neutron background of less than one event per month. A blind analysis of an efficiency-corrected 1167-kg day exposure at a 3.3-keV thermodynamic threshold reveals no single-scattering nuclear recoil candidates, consistent with the predicted background. These results set the most stringent direct-detection constraint to date on the weakly interacting massive particle (WIMP)-proton spin-dependent cross section at 3.4×10^{-41} cm^{2} for a 30-GeV c^{-2} WIMP, more than 1 order of magnitude improvement from previous PICO results.

Dark Matter Search Results from the PICO-2L C3F8 Bubble Chamber.

New data are reported from the operation of a 2 liter C3F8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C3F8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of <3.5×10(-10) and an alpha rejection factor of >98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed during the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. These data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.

Improved limits on spin-dependent WIMP-proton interactions from a two liter CF3I bubble chamber.

Data from the operation of a bubble chamber filled with 3.5 kg of CF3I in a shallow underground site are reported. An analysis of ultrasound signals accompanying bubble nucleations confirms that alpha decays generate a significantly louder acoustic emission than single nuclear recoils, leading to an efficient background discrimination. Three dark matter candidate events were observed during an effective exposure of 28.1 kg day, consistent with a neutron background. This observation provides strong direct detection constraints on weakly interacting massive particle (WIMP)-proton spin-dependent scattering for WIMP masses >20 GeV/c2.

The role of modern imaging modalities on deep brain stimulation targeting for mental illness.

INTRODUCTION: The reversible nature of deep brain stimulation (DBS) brought renewed interest on surgery to medically intractable mental illnesses. The explosion of anatomical and functional imaging has allowed the development of new potential targets and the understanding of historical targets. METHODS: Fifteen patients undergoing stereotactic surgery for movement disorders, at UCLAs interventional MRI operating-room, were studied with fiber tracking. Stereotactic targets and fiber tracking were determined on MRIs using the Schaltenbrand-Wahren atlas for definition in the iPlan software. Cingulate, subcaudate, BA25/CgWM, amygdala, posterior hypothalamus, orbitofrontal cortex, nucleus accumbens, anterior limb of the internal capsule and dorsomedial thalamus were studied. DTI parameters used ranged from 10 to 20mm for voxel size in the x/y/z planes, fiber length was kept constant at 36 mm, and fractional anisotropy (FA) threshold varied from 0.20 to 0.25. RESULTS: Reliable interconnectivity of targets were determined with DTI and related to PET imaging. Mental illness targets were observed with functional and fiber tract maps. This confirmation yields reliability to DTI imaging in order to determine novel targets and enhance the understanding of areas not well understood. CONCLUSIONS: Currently available imaging techniques, the reversibility of DBS to modulate targets promises to bring a brighter future for surgery of mental illness.

Spin-dependent WIMP limits from a bubble chamber.

Bubble chambers were the dominant technology used for particle detection in accelerator experiments for several decades, eventually falling into disuse with the advent of other techniques. We report here on a new application for these devices. We operated an ultraclean, room-temperature bubble chamber containing 1.5 kilograms of superheated CF3I, a target maximally sensitive to spin-dependent and -independent weakly interacting massive particle (WIMP) couplings. An extreme intrinsic insensitivity to the backgrounds that commonly limit direct searches for dark matter was measured in this device under operating conditions leading to the detection of low-energy nuclear recoils like those expected from WIMPs. Improved limits on the spin-dependent WIMP-proton scattering cross section were extracted during our experiments, excluding this type of coupling as a possible explanation for a recent claim of particle dark-matter detection.

Simulation of special bubble detectors for PICASSO.

The PICASSO project is a cold dark matter (CDM) search experiment relying on the superheated droplet technique. The detectors use superheated freon liquid droplets (active material) dispersed and trapped in a polymerised gel. This detection technique is based on the phase transition of superheated droplets at about room temperature and ambient pressure. The phase transition is induced by nuclear recoils when an atomic nucleus in the droplets interacts with incoming subatomic particles. This includes CDM particles candidate as the neutralino (a yet-to-discover particle predicted in extensions of the standard model of particle physics). Simulations performed to understand the detector response to neutrons and alpha particles are presented along with corresponding data obtained at the Montreal Laboratory.

Direct dark matter search using large-mass superheated droplet detectors in the PICASSO experiment.

The PICASSO experiment investigates the presence and nature of dark matter in the Universe. The experiment is based on the detection of acoustic signals generated in explosive phase transitions induced by dark matter particles. This technique is an alternative more traditional detection technique like scintillation and ionisation, which are largely employed for dark matter search. One of the main advantages of this technique, besides its sensitivity to very low nuclear recoil energies (few keV), is its excellent background suppression features. A pilot experiment consisting of six superheated droplet detectors (40 g of active mass) is presently taking data at the Sudbury Neutrino Observatory (SNO) at a depth of 2000 m. We discuss the operation, calibration and data acquisition of the experiment and also the ongoing work to increase the sensitivity and the active mass of the detectors.

Deep brain stimulation in intraoperative MRI environment - comparison of imaging techniques and electrode fixation methods.

We performed 118 consecutive DBS cases from November 1999 to June 2002. Intraoperatively there were 10 cases studied with fluoroscopy, 73 with 0.2 Tesla (T) MRI and 35 with 1.5 T MRI. Ten electrodes were secured by Medtronic caps, 25 by methyl methacrylate with titanium miniplates, and 82 by Navigus caps. The 3-dimensional displacement between the planned target and actual electrode position (3DD) was determined by fusing the postoperative MRI with the preoperative imaging. The 3DD for using Medtronic caps, methyl methacrylate with miniplates, and Navigus caps were 4.80 +/- 3.16, 2.64 +/- 1.26 and 2.23 +/- 1.15 mm (mean +/- SD), respectively. Navigus caps had statistically significant accuracy (P = 0.03) in holding the electrode when compared with Medtronic caps, and it facilitated electrode revision. The fixation devices significantly affect the final vertical position of the electrode. The 3DD for fluoroscopy, 0.2 T and 1.5 T MRI cases were 4.80 +/- 3.16, 2.31 +/- 1.21 and 2.34 +/- 1.14 mm (mean +/- SD), respectively. No statistically significant difference (P = 0.91) in 3DD was demonstrated between 0.2 T and 1.5 T MRI cases. The presence of intraoperative 1.5 T MRI allowed near real-time electrode position confirmation and early detection of hemorrhagic complications. Satisfactory microelectrode recording was feasible in low-field 0.2 T and high-field 1.5 T MRI environments. Further studies on performing DBS in real-time intraoperative MRI are warranted.

Functional neurosurgery in the MRI environment.

OBJECTIVE: The purpose of this study was to evaluate the feasibility of microelectrode recording, electrical stimulation, and electrode position checking during functional neurosurgical procedures (DBS, lesion) in the interventional magnetic resonance imaging (iMRI) environment. METHODS: Seventy-six surgical procedures for DBS implant or radiofrequency lesion were performed in an open 0.2 T MRI operating room. DBS implants were performed in 54 patients (72 surgical procedures) and unilateral radiofrequency lesions in three for a total of 76 surgeries in 57 patients. Electrophysiological studies including macrostimulation and microelectrode recordings for localization were obtained in the 0.5 to 10 mT fringes of the magnetic field in 51 surgeries. MRI confirmation of the electrode position during the procedure was performed after electrophysiological localization. RESULTS: The magnetic field associated with the MRI scanner did not contribute significant noise to microelectrode recordings. Anatomical confirmation of electrode position was possible within the MRI artifact from the DBS hardware. Symptomatic hemorrhage was detected in two (2.6 %) patients during the operation. Image quality of the 0.2 T MRI scan was sub-optimal for anatomical localization. However, image fusion with pre-operative scans permitted excellent visualization of the DBS electrode tip in relation to the higher quality 1.5 T MRI anatomical scans. CONCLUSION: This study shows that conventional stereotactic localization, microelectrode recordings, electrical stimulation, implant of DBS hardware, and radiofrequency lesion placement are possible in the open 0.2 T iMRI environment. The convenience of having an imaging modality that can visualize the brain during the operation is ideal for stereotactic procedures.

Subclinical myocardial injury in small-for-gestational-age neonates.

OBJECTIVE: Small-for-gestational-age (SGA) infants are at risk for premature death from cardiovascular disease (myocardial infarction and stroke), hypertension, and diabetes in adult life. Severe intrauterine growth restriction is often associated with subclinical cardiovascular abnormalities detectable during fetal echocardiography. The objective of this study was to determine whether SGA newborns have evidence of myocardial injury at birth. STUDY DESIGN: Cardiac troponin I, a specific marker of myocardial injury widely used for the diagnosis of myocardial infarction in adults, was determined in umbilical cord blood. Umbilical cord venous blood was obtained at the time of birth from 72 SGA newborns (birth weight below the 10th centile for gestational age) and 309 newborns whose birth weights were appropriate for gestational age (AGA). Cardiac troponin I was determined with a commercially available immunoassay (sensitivity 0.2 ng/ml) employed in clinical laboratories (Immulite 2000, Diagnostic Products Corp., Los Angeles, CA). RESULTS: Cardiac troponin I was not detectable in any of the blood samples from AGA infants. In contrast, 4.2% (3/72) of SGA infants had detectable cardiac troponin I in umbilical cord blood (Fisher's exact test, p = 0.007). CONCLUSION: A subgroup of SGA newborns undergoes myocardial injury before birth. This insult may predispose to the development of adult premature cardiovascular disease and death.

Ultradian sleep-cycle variation of serotonin in the human lateral ventricle.

Serotonin is thought to be intimately involved in the regulation of sleep and waking in humans, though the evidence for such is indirect. Using in vivo microdialysis, the authors show that serotonin in human ventricular CSF covaries with the state of consciousness. They hypothesize that CSF serotonin may be acting in an endocrine-like manner through activation of known leptomeningeal serotonin receptors and possibly participating in modulation of choroidal production of CSF.

Staged bilateral pallidotomy for treatment of Parkinson disease.

OBJECT: Several investigators have described the motor benefits derived from performing unilateral stereotactic pallidotomy for the treatment of Parkinson disease (PD), but little is known about the efficacy and complication rates of bilateral procedures. The goal of this study was to assess both these factors in 12 patients. METHODS: Eleven patients with medically intractable PD underwent staged bilateral pallidotomy and one patient underwent a simultaneous bilateral procedure. Unilateral pallidotomy resulted in an improvement in the patients' Unified Parkinson Disease Rating Scale (UPDRS) total scores and motor subscores, Hoehn and Yahr stages, and Schwab and England Activities of Daily Living scores. There were no complications. The second procedures were performed 5 to 25 months after the first, and nearly complete 3-month follow-up data are available for eight of these patients. Staged bilateral pallidotomy did result in further improvements in some symptoms, but the patients proved to be less responsive to levodopa. In contrast to outcomes of the initial unilateral pallidotomy, there were significant complications. One patient suffered an acute stroke, two patients suffered delayed infarctions of the internal capsule, four patients had mild-to-moderate worsening of speech and increased drooling, and one patient complained of worsening memory. CONCLUSIONS: Bilateral pallidotomy results in modest benefits but is associated with an increased risk of complications.

Increased dopamine release in the human amygdala during performance of cognitive tasks.

Accumulating data support a critical involvement of dopamine in the modulation of neuronal activity related to cognitive processing. The amygdala is a major target of midbrain dopaminergic neurons and is implicated in learning and memory processes, particularly those involving associations between novel stimuli and reward. We used intracerebral microdialysis to directly sample extracellular dopamine in the human amygdala during the performance of cognitive tasks. The initial transition from rest to either a working memory or a reading task was accompanied by significant increases in extracellular dopamine concentration of similar magnitude. During a sustained word paired-associates learning protocol, increase in dopamine release in the amygdala related to learning performance. These data provide evidence for sustained activation of the human mesolimbic dopaminergic system during performance of cognitive tasks.

Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. Technical note.

Monitoring physiological changes in the brain parenchyma has important applications in the care of neurosurgical patients. A technique is described for measuring extracellular neurochemicals by cerebral microdialysis with simultaneous recording of electroencephalographic (EEG) and single-unit (neuron) activity in selected targets in the human brain. Forty-two patients with medically intractable epilepsy underwent stereotactically guided implantation of a total of 423 intracranial depth electrodes to delineate potentially resectable seizure foci. The electrodes had platinum alloy contacts for EEG recordings and four to nine 40-microm microwires for recording single-unit neuron activity. Eighty-six electrodes also included microdialysis probes introduced via the electrode lumens. During monitoring on the neurosurgical ward, electrophysiological recording and cerebral microdialysis sampling were performed during seizures, cognitive tasks, and sleep-waking cycles. The technique described here could be used in developing novel approaches for evaluation and treatment in a variety of neurological conditions such as head injury, subarachnoid hemorrhage, epilepsy, and movement disorders.

Correlation between MRI-based stereotactic thalamic deep brain stimulation electrode placement, macroelectrode stimulation and clinical response to tremor control.

In this study we compared the position of the electronically active contact of the thalamic (Vim) deep brain stimulation (DBS) electrode to the stereotactic location of its tip. Fifteen patients with either Parkinson's disease (PD) or essential tremor (ET) underwent stereotactic, MRI-based placement of the Medtronic quadripolar DBS electrode. An overall improvement of 69% was achieved in the tremor scores during a period of 1-13 months after implantation of the DBS electrode. Eleven patients with ET showed 70% clinical improvement of tremor, compared to a 58% response observed in the 4 patients with PD. The electrode tip center was 11.2 +/- 1.54 mm lateral to the third ventricular wall, 5.38 +/- 1.02 mm anterior to the posterior commissure and 2.9 +/- 3.57 mm inferior to the level of AC-PC line. The most significant deviation from the planned stereotactic target was observed in the Z-coordinate. In our group of patients, stimulation settings favored the contacts closer to the AC-PC line, correcting the electrode tip position to 0.80 +/- 2.84 mm (p < 0.001) inferior to the level of the AC-PC line. In our experience, thalamic DBS offers a reversible and adjustable 'lesion' to compensate for the anatomic variabilities encountered in the positioning of the DBS electrode tip.

Motor, cognitive, and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson disease.

OBJECTIVE: To evaluate the effects of ventroposterior pallidotomy on motor disability and on behavior and cognition in patients with medically intractable idiopathic Parkinson disease. DESIGN: Detailed motor testing both while receiving and discontinuing levodopa medication, posturography, and neurocognitive and behavioral assessments were performed before and 3 to 6 months after unilateral ventroposterior pallidotomy. SETTING: University-based movement disorder program. PATIENTS: Thirty-two patients without dementia with medically refractory idiopathic Parkinson disease were studied. MAIN OUTCOME MEASURES: Motor function and disability were measured using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and the Schwab and England Activities of Daily Living Scale. Dynamic balance was measured by sway (amplitude and velocity) using the Chattecx Balance System. Detailed cognitive and behavioral assessments were also performed both before and after surgery. RESULTS: Eighty-three percent of patients experienced improvement of their total Unified Parkinson's Disease Rating Scale score at 3 to 6 months after surgery. Significant improvements were also seen in the contralateral Unified Parkinson's Disease Rating Scale motor subscore (78%) as well as in the contralateral Unified Parkinson's Disease Rating Scale total score both during the on and off period (78% and 79%, respectively). The Hoehn and Yahr stage, Schwab and England Activities of Daily Living Scale score, and dynamic balance when standing on foam also improved following unilateral pallidotomy in many patients. Cognitive performance remained relatively unchanged following surgery with the exception of category fluency, which exhibited a modest decline (P < .04). A significant improvement in depression was found on the Beck Depression Inventory. CONCLUSIONS: Ventroposterior pallidotomy significantly improves motor performance and daily level of function in Parkinson disease. Cognition and behavior are not adversely affected in patients without dementia, and a cognitive screening battery is proposed.

Paired pulse suppression and facilitation in human epileptogenic hippocampal formation.

Paired pulse stimulation has commonly been employed to investigate changes in excitability in epileptic hippocampal tissue employing the in vitro slice preparation. We used paired pulse stimulation in the intact temporal lobe of patients with temporal lobe seizures to compare the excitability of pathways in the epileptogenic hippocampus (located in the temporal lobe in which seizures arise) with those in the non-epileptogenic hippocampus of the contralateral temporal lobe (in the hemisphere to which seizures spread). A total of 20 patients with temporal lobe seizure onsets were studied during chronic depth electrode monitoring for seizure localization. Intracranial in vivo stimulation and recording sites included the hippocampus, entorhinal cortex, subicular cortex and parahippocampal gyrus. A comparison of all hippocampal pathways located in the temporal lobe where seizures typically started (n = 37) with those in temporal lobes contralateral to seizure onset (n = 53) showed significantly greater paired pulse suppression of population post-synaptic potentials on the epileptogenic side (F(1,87) = 6.1, P < 0.01). Similarly, mean paired pulse suppression was significantly greater for epileptogenic perforant path responses than for contralateral perforant path responses (F(1,13) = 7.5, P < 0.01). In contrast, local stimulation activating intrinsic associational pathways of the epileptogenic hippocampus showed decreased paired pulse suppression in comparison to the epileptogenic perforant path. These results may be a functional consequence of the formation of abnormal recurrent inhibitory and recurrent excitatory pathways in the sclerotic hippocampus. Enhanced inhibition may be adaptive in suppressing seizures during interictal periods, while abnormal recurrent excitatory circuits in the presence of enhanced inhibition may drive the hypersynchronization of principal neurons necessary for seizure genesis.

Birth of a western lowland gorilla (Gorilla gorilla gorilla) following in vitro fertilization and embryo transfer.

A 21-year-old multiparous female exhibiting 31-41 day menstrual cycles was given hFSH (225 IU/day, Metrodin 75, from cycle day 3 through 9 (menses = day 1) and hCG (10,000 IU, Profasi, on day 10 to stimulate follicular development. At 35 h after hCG, under isoflurane (AErrane) anesthesia, follicles were aspirated by controlled suction under transvaginal ultrasound guidance. Metaphase II oocytes (n = 11) were placed in modified human tubal fluid (mHTF, 100 microliters) medium under oil at 37 degrees C in humidified 5% CO2. Frozen semen, collected by voluntary ejaculation, was thawed (70 degrees C H2O bath, 6 sec), diluted slowly, centrifuged, and resuspended in mHTF, and 160,000 motile spermatozoa/ml were added at 6 h after oocyte recovery. At 21 h postinsemination (p.i.) eight oocytes were at the two-cell stage, five were cryopreserved, and three were cultured to the six- to eight-cell stage in mHTF with granulosa cells before transcervical uterine transfer at 47 h p.i. using a Teflon catheter. Micronized progesterone (400 mg/d) was orally administered for 10 weeks posttransfer (p.t.). Ultrasound examination revealed a single fetus at 15 weeks p.t., and unassisted delivery of a live 1.37 kg female infant occurred at 29 weeks. Am. J. Primatol. 41:247-260, 1997.