Corrigendum to "Neural distinctiveness and discriminability underlying unitization and associative memory in aging" [Aging Brain 4 (2023) 100097].

[This corrects the article DOI: 10.1016/j.nbas.2023.100097.].

Neural distinctiveness and discriminability underlying unitization and associative memory in aging.

Previous work has suggested unitized pairs behave as a single unit and more critically, are processed neurally different than those of associative memories. The current works examines the neural differences between unitization and non-unitized memory using fMRI and multivoxel analyses. Specifically, we examined the differences across face-occupation pairings as a function of whether the pairing was viewed as a person performing the given job (unitized binding) or a person saying they knew someone who had a particular job (non-unitized binding). The results show that at encoding and retrieval, the angular gyrus can discriminate between unitized and non-unitized target trials. Additionally, during encoding, the medial temporal lobe (hippocampus and perirhinal cortex), frontal parietal regions (angular gyrus and medial frontal gyrus) and visual regions (middle occipital cortex) exhibit distinct neural patterns to recollected unitized and non-unitized targets. Furthermore, the perirhinal cortex and medial frontal gyrus show greater neural similarity within subsequently recollected unitized trials compared to non-unitized trials. We conclude that an encoding based strategy to elicit unitization can produce greater associative memory compared to non-unitized trials in older adults. Additionally, when unitized trials are subsequently recollected in the perirhinal cortex older adults show greater neural similarity within unitized trials compared to non-unitized trials.

Neural distinctiveness and reinstatement of hippocampal representations support unitization for associations.

The medial temporal lobe (MTL) is critical to associative memory success, yet not all types of associations may be processed in a similar manner within MTL subregions. In particular, previous work suggests intra- and inter-item associations not only exhibit differences in overall rates of recollection, but also recruit different MTL subregions. Whereas intra-item associations, akin to unitization, take advantage of associations between within-item features, inter-item associations form links across discrete items. The current work examines the neural differences between these two types of associations using fMRI and multivoxel analyses. Specifically, the current study examines differences across face-occupation as a function of whether the pairing was viewed as a person performing the given job (intra-item binding) or a person saying they knew someone who had a particular job (inter-item binding). The results show that at encoding, successfully recollected neural patterns related to intra- and inter-item associations are distinct from one another in the hippocampus, parahippocampal and perirhinal cortex. Additionally, the two trial types are reinstated distinctly such that inter-item trials have higher neural reinstatement from encoding to retrieval compared to intra-item trials in the hippocampus. We conclude that intra- and inter- associative pairs may utilize similar neural regions that represent patterns of activation differentially at encoding. However, to reinstate information to the same degree (i.e., subsequently successfully recollected) inter-item associations, that are all encoded in the same manner, may be reinstated more similarly compared to intra-item associations that are encoded by imagining pairs differently and occupation specific. This may indicate that intra-item associations promote more efficient reinstatement.

Within-category similarity negatively affects associative memory performance in both younger and older adults.

Associative memory involves the ability to encode and remember the relationship between individual items. This ability can become diminished when there is a high degree of similarity between stimuli that are being learned. Associative memory errors often stem from the fact that lures include a high degree of item familiarity as well as mnemonic similarity with the original associative episode. The current set of experiments examined how this overlap, in the form of within-category similarity, affects veridical and false retrieval in both younger and older adults. Across three experiments, results suggest that mnemonic overlap between targets and lures is detrimental to the ability to discriminate between highly similar information. Specifically, shared category membership for targets and lures led to increased false associative memories across age groups. These results have implications for scenarios where there is a high degree of overlap between target and lure events and indicate that these types of associative memory distinctions are difficult irrespective of age.

Limited-angle x-ray luminescence tomography: methodology and feasibility study.

X-ray luminescence tomography (XLT) has recently been proposed as a new imaging modality for biological imaging applications. This modality utilizes phosphor nanoparticles which luminesce near-infrared light when excited by x-ray photons. The advantages of this modality are that it uniquely combines the high sensitivity of radioluminescent nanoparticles and the high spatial localization of collimated x-ray beams. Currently, XLT has been demonstrated using x-ray spatial encoding to resolve the imaging volume. However, there are applications where the x-ray excitation may be limited by geometry, where increased temporal resolution is desired, or where a lower dose is mandatory. This paper extends the utility of XLT to meet these requirements by incorporating a photon propagation model into the reconstruction algorithm in an x-ray limited-angle (LA) geometry. This enables such applications as image-guided surgery, where the ability to resolve lesions at depths of several centimeters can be the key to successful resection. The hybrid x-ray/diffuse optical model is first formulated and then demonstrated in a breast-sized phantom, simulating a breast lumpectomy geometry. Both numerical and experimental phantoms are tested, with lesion-simulating objects of various sizes and depths. Results show localization accuracy with median error of 2.2 mm, or 4% of object depth, for small 2-14 mm diameter lesions positioned from 1 to 4.5 cm in depth. This compares favorably with fluorescence optical imaging, which is not able to resolve such small objects at this depth. The recovered lesion size has lower size bias in the x-ray excitation direction than the optical direction, which is expected due to the increased optical scatter. However, the technique is shown to be quite invariant in recovered size with respect to depth, as the standard deviation is less than 2.5 mm. Sensitivity is a function of dose; radiological doses are found to provide sufficient recovery for µg ml(-1) concentrations, while therapy dosages provide recovery for ng ml(-1) concentrations. Experimental phantom results agree closely with the numerical results, with positional errors recovered within 8.6% of the effective depth for a 5 mm object, and within 5.2% of the depth for a 10 mm object. Object-size median error is within 2.3% and 2% for the 5 and 10 mm objects, respectively. For shallow-to-medium depth applications where optical and radio-emission imaging modalities are not ideal, such as in intra-operative procedures, LAXLT may be a useful tool to detect molecular signatures of disease.

Hybrid x-ray/optical luminescence imaging: characterization of experimental conditions.

PURPOSE: The feasibility of x-ray luminescence imaging is investigated using a dual-modality imaging system that merges x-ray and optical imaging. This modality utilizes x-ray activated nanophosphors that luminesce when excited by ionizing photons. By doping phosphors with lanthanides, which emit light in the visible and near infrared range, the luminescence is suitable for biological applications. This study examines practical aspects of this new modality including phosphor concentration, light emission linearity, detector damage, and spectral emission characteristics. Finally, the contrast produced by these phosphors is compared to that of x-ray fluoroscopy. METHODS: Gadolinium and lanthanum oxysulfide phosphors doped with terbium (green emission) or europium (red emission) were studied. The light emission was imaged in a clinical x-ray scanner with a cooled CCD camera and a spectrophotometer; dose measurements were determined with a calibrated dosimeter. Using these properties, in addition to luminescence efficiency values found in the literature for a similar phosphor, minimum concentration calculations are performed. Finally, a 2.5 cm agar phantom with a 1 cm diameter cylindrical phosphor-filled inclusion (diluted at 10 mg/ml) is imaged to compare x-ray luminescence contrast with x-ray fluoroscopic contrast at a superficial location. RESULTS: Dose to the CCD camera in the chosen imaging geometry was measured at less than 0.02 cGy/s. Emitted light was found to be linear with dose (R(2)= 1) and concentration (R(2)= 1). Emission peaks for clinical x-ray energies are less than 3 nm full width at half maximum, as expected from lanthanide dopants. The minimum practical concentration necessary to detect luminescent phosphors is dependent on dose; it is estimated that subpicomolar concentrations are detectable at the surface of the tissue with typical mammographic doses, with the minimum detectable concentration increasing with depth and decreasing with dose. In a reflection geometry, x-ray luminescence had nearly a 430-fold greater contrast to background than x-ray fluoroscopy. CONCLUSIONS: X-ray luminescence has the potential to be a promising new modality for enabling molecular imaging within x-ray scanners. Although much work needs to be done to ensure biocompatibility of x-ray exciting phosphors, the benefits of this modality, highlighted in this work, encourage further study.

Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging.

PURPOSE: The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen/ carbogen, air/carbogen, and air/oxygen) was investigated. METHODS: Subjects breathed combinations of gases which were modulated in time. MR-guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air/air control to determine the hemodynamic changes compared to the baseline physiology. RESULTS: This study demonstrated that a gas stimulus consisting of alternating oxygen/carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air/oxygen or air/carbogen modulated breathing protocols. CONCLUSIONS: MR-guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements.

Developing smokeless tobacco products for smokers: an examination of tobacco industry documents.

OBJECTIVE: To investigate whether development of smokeless tobacco products (SLT) is intended to target current smokers. METHODS: This study analysed internal tobacco industry documents to describe research related to the smokeless tobacco market. Relevant documents included those detailing the development and targeting of SLT products with a particular emphasis on moist snuff. RESULTS: Cigarette and SLT manufacturers recognised that shifting demographics of SLT users, as well as indoor smoking restrictions, health concerns and reduced social acceptability of smoking could impact the growth of the SLT market. Manufacturers developed new SLT products to target cigarette smokers promoting dual cigarette and SLT use. CONCLUSIONS: Heavy marketing of new SLT products may encourage dual use and result in unknown public health effects. SLT products have been designed to augment cigarette use and offset regulatory strategies such as clean indoor air laws. In the United States, the SLT strategy may provide cigarette companies with a diversified range of products under the prospect of federal regulation. These products may pose significant challenges to efforts by federal agencies to reduce harm caused by tobacco use.

Comparison of the antibody in lymphocyte supernatant (ALS) and ELISPOT assays for detection of mucosal immune responses to antigens of enterotoxigenic Escherichia coli in challenged and vaccinated volunteers.

In the present study we compared the ELISPOT and antibody in lymphocyte supernatants (ALS) assays as surrogate measures of mucosal immunity. In separate studies, 20 inpatient volunteers received oral doses of 6 x 10(8) or 4 x 10(9)cfu of ETEC strain E24377A (LT+, ST+, CS1+, CS3+) and 20 subjects received 1 (n = 9) or 2 (n = 11) oral doses of the attenuated ETEC vaccine, PTL-003 expressing CFA/II (CS1+ and CS3+) (2 x 10(9)cfu/dose). Peripheral blood mononuclear cells (PBMCs) from all subjects were assayed for anti-colonization factor or toxin-specific IgA antibody responses using the ALS and ELISPOT procedures. ALS responses were measured using a standard ELISA, as well as by time-resolved fluorescence (TRF). Following challenge with E24377A, significant anti-CS3, CS1 and LT ALS responses were detected in the lymphocyte supernatants of 75-95% of the subjects. A similar proportion (75%) of subjects mounted an ALS response to CFA/II antigen after vaccination with the PTL-003 vaccine. Inter-assay comparisons between ALS and ELISPOT methods also revealed a high degree of correlation in both immunization groups. ALS sensitivity versus the ELISPOT assay for LT, CS3 and CS1-specific responses following challenge were 95%, 94% and 78%, respectively and 83% for the ALS response to CFA/II antigen after vaccination with PTL-003. Correlation coefficients for the LT and CS3 antigens were 0.94 (p<0.001) and 0.82 (p<0.001), respectively after challenge and 0.78 (p<0.001) after vaccination. The association between ALS and ELISPOT for the CS1 antigen was however, significant only when ALS supernatants were tested by TRF (r = 0.91, p<0.001). These results demonstrate the value and flexibility of the ALS assay as an alternative to ELISPOT for the measurement of mucosal immune responses to ETEC antigens, particularly when the complexities of ELISPOT may make it impractical to perform.

Expression of 70 kDa heat shock proteins in antarctic and New Zealand notothenioid fish.

The cold and constant water temperature of the Southern Ocean surrounding Antarctica provides a natural laboratory to address questions of temperature adaptation in marine organisms. In this study, endogenous levels and the number of isoforms of the 70 kDa heat shock protein multigene family (hsp70) of Antarctic and cold temperate notothenioid fishes were determined by SDS-polyacrylamide gel electrophoresis and Western blotting. Tissues from three Antarctic Trematomus congeners had significantly lower levels of 70 kDa Hsp isoforms than their temperate confamilial from New Zealand waters. However, these two thermally disparate sets of fish did not differ in number or pattern of 70 kDa Hsp isoforms expressed under normal physiological conditions. Additionally, levels of 70 kDa Hsp isoforms in specimens of one Antarctic species, Trematomus bernacchii, acclimated to 4 degrees C were significantly higher than non-acclimated conspecifics, indicating a direct effect of temperature on Hsp expression in this species. This study shows that constitutive expression of some members of the 70 kDa Hsp multigene family have been maintained, despite the absence of environmental heat stress for at least 2.5 million years.

Runaway pacemaker in an implantable cardioverter defibrillator.

INTRODUCTION: Runaway pacemaker is a potentially catastrophic complication of any permanent pacing system. METHODS AND RESULTS: A 70-year-old man was found to have erratic behavior of his implantable cardioverter defibrillator (ICD) during a routine outpatient interrogation. His device was turned off, and he was hospitalized in preparation for a pulse generator replacement. During his hospitalization, his ICD unexpectedly began pacing rapidly. Despite prompt resuscitation attempts, the patient died. Postmortem examination of the device demonstrated a crystal oscillator failure. CONCLUSION: A previously unrecognized component malfunction is a potentially lethal complication of ICDs.

Drug therapy for atrial fibrillation--interactions with interventional therapy and implications for local drug delivery.

Multiple therapeutic alternatives, both pharmacological and non-pharmacological, are under active investigation for the treatment of atrial fibrillation. Although many promising approaches are being investigated, there is as yet no universally accepted therapy, nor is there likely to be in the foreseeable future. It is possible that, since no one therapeutic intervention is ideal, a combination of pharmacological and non-pharmacological approaches may succeed in patients in whom neither therapy alone would be effective. In this paper, we explore interactions between devices and antiarrhythmic drugs, as well as novel methods of delivering anti-arrhythmic drug therapy.

Radiologic dilatation preceding palliative surgical tube placement for esophageal cancer.

A new two-stage technique is reported for tube placement in the palliative treatment of esophageal cancer. The first step consists of radiologic intervention with balloon dilatation of the stricture. The patient is then transferred to the operating room, where the permanent esophageal tube placement is performed. A comparison of technique-related complications in a group of 34 patients with esophageal malignancies who had a permanent tube inserted by either the two-stage technique or by a standard endoscopic operative method show the new technique to have fewer complications and markedly decreased operative time.

Neodymium yttrium aluminum garnet laser treatment of hemobilia via a percutaneous biliary catheter track.

The authors describe the use of neodymium yttrium aluminum garnet laser introduced via a percutaneous catheter track for photocoagulation of a bleeding bile duct tumor.

Discordance in the sizing of abdominal aortic aneurysm and its significance.

Much of the confusion surrounding the repair of asymptomatic abdominal aortic aneurysms related to inaccuracies in their measurement, both preoperatively and intraoperatively. Multiple measurements of aneurysms at operation have convinced us that the largest and least variable diameter is the anteroposterior diameter measured from aortic wall anteriorly to vertebral bodies posteriorly. This AP-to-spine distance is accurately predicted by ultrasonography to within 0.3 cm. Computerized tomography does no better. plain radiography is accurate but seldom applicable. When properly estimated, aneurysm size can be accurately determined preoperatively by either ultrasonography, computerized tomography, or plain radiography, in that order of preference. Since the decision to operate on asymptomatic aneurysms is based largely on their size, accurate preoperative estimation is essential.

Management of central venous catheters using a wire introducer.

The wire introducer method is a satisfactory technique for management of central venous catheters if bacteriologic monitoring of the removed catheter is used to determine whether the introduced catheter should be allowed to remain. The data indicate that when central venous catheters become infected, they do so through the whole length of the catheter, from subcutaneous tunnel to intravascular tip. An intravenous catheter which produces negative cultures can be safely changed by the introducer method aseptically. An infected catheter must be removed as soon as the diagnosis is apparent, since the replacement catheter will be seeded by the colonized tract. Blood specimens drawn through central venous lines do not reflect the status of the line itself but rather the presence or absence of systemic bacteremia.

Re-examination of histocompatibility antigens found in patients with juvenile rheumatoid arthritis.

One hundred and twenty-three patients with juvenile rheumatoid arthritis and a similar number of controls were tissue typed for 30 HL-A antigens to determine if there were any associations between particular HL-A antigens and the disease. None were found. However, HL-A7 was found more frequently in patients with juvenile rheumatoid arthritis demonstrating tenosynovitis than in the population with juvenile rheumatoid arthritis as a whole. These observations fail to support the contention of others that HL-A-W27 is found more frequently than expected in such patients.