Enhanced axillary assessment using intradermally injected microbubbles and contrast-enhanced ultrasound (CEUS) before neoadjuvant systemic therapy (NACT) identifies axillary disease missed by conventional B-mode ultrasound that may be clinically relevant.

PURPOSE: The purpose of this study is to measure pre-treatment diagnostic yield of malignant lymph nodes (LN) using contrast-enhanced ultrasound (CEUS) in addition to B-mode axillary ultrasound and compare clinicopathological features, response to NACT and long-term outcomes of patients with malignant LN detected with B-mode ultrasound versus CEUS. METHODS: Between August 2009 and October 2016, NACT patients were identified from a prospective database. Follow-up data were collected until May 2019. RESULTS: 288 consecutive NACT patients were identified; 77 were excluded, 110 had malignant LN identified by B-mode ultrasound (Group A) and 101 patients with negative B-mode axillary ultrasound had CEUS with biopsy of sentinel lymph nodes (SLN). In two cases CEUS failed. Malignant SLN were identified in 35/99 (35%) of B-mode ultrasound-negative cases (Group B). Patients in Group A were similar to those in Group B in age, mean diagnostic tumour size, grade and oestrogen receptor status. More Group A patients had a ductal phenotype. In the breast, 34 (31%) Group A patients and 8 (23%) Group B patients achieved a pathological complete response (PCR). In the axilla, 41 (37%) and 13 (37%) Groups A and B patients, respectively, had LN PCR. The systemic relapse rate was not statistically different (5% and 16% for Groups A and B, respectively). CONCLUSIONS: Enhanced assessment with CEUS before NACT identifies patients with axillary metastases missed by conventional B-mode ultrasound. Without CEUS, 22 (63%) of cases in Group B (negative B-mode ultrasound) may have been erroneously classed as progressive disease by surgical SLN excision after NACT.

Holding On to the Past: Older Adults Show Lingering Neural Activation of No-Longer-Relevant Items in Working Memory.

Goal-relevant information can be maintained in working memory over a brief delay interval to guide an upcoming decision. There is also evidence suggesting the existence of a complementary process: namely, the ability to suppress information that is no longer relevant to ongoing task goals. Moreover, this ability to suppress or inhibit irrelevant information appears to decline with age. In this study, we compared younger and older adults undergoing fMRI on a working memory task designed to address whether the modulation of neural representations of relevant and no-longer-relevant items during a delay interval is related to age and overall task performance. Following from the theoretical predictions of the inhibitory deficit hypothesis of aging, we hypothesized that older adults would show higher activation of no-longer-relevant items during a retention delay compared to young adults and that higher activation of these no-longer-relevant items would predict worse recognition memory accuracy for relevant items. Our results support this prediction and more generally demonstrate the importance of goal-driven modulation of neural activity in successful working memory maintenance. Furthermore, we showed that the largest age differences in the regulation of category-specific pattern activity during working memory maintenance were seen throughout the medial temporal lobe and prominently in the hippocampus, further establishing the importance of "long-term memory" retrieval mechanisms in the context of high-load working memory tasks that place large demands on attentional selection mechanisms.

Spontaneous Distractor Reactivation With Age: Evidence for Bound Target-Distractor Representations in Memory.

Reduced attentional control with age is associated with the processing and maintenance of task-irrelevant information in memory. Yet the nature of these memory representations remains unclear. We present evidence that, relative to younger adults (n = 48), older adults (n = 48) both (a) store simultaneously presented target and irrelevant information as rich, bound memory representations and (b) spontaneously reactivate irrelevant information when presented with previously associated targets. In a three-stage implicit reactivation paradigm, re-presenting a target picture that was previously paired with a distractor word spontaneously reactivated the previously associated word, making it become more accessible than an unreactivated distractor word in a subsequent implicit memory task. The accessibility of reactivated words, indexed by priming, was also greater than the degree of distractor priming shown by older adults in a control condition (n = 48). Thus, reduced attentional control influences the processing and representation of incoming information.

Contrast-Enhanced Ultrasound Biopsy of Sentinel Lymph Nodes in Patients with Breast Cancer: Implications for Axillary Metastases and Conservation.

BACKGROUND: In breast cancer patients, sentinel lymph nodes (SLN) can be identified in the breast clinic using contrast-enhanced ultrasound (CEUS). This study aimed to characterize and compare the extent of axillary metastases in patients with either a benign or malignant SLN core biopsy at the end of surgical treatment. METHODS: Between 2009 and 2014, prospective data were collected on consecutive patients who underwent targeted core biopsy of SLN identified using CEUS in the breast clinic. Patients with abnormal lymph nodes (LN) detected on grey-scale ultrasound were not included. Patients whose initial SLN core biopsy was benign were compared with those who had a malignant SLN core biopsy. RESULTS: 555 patients with invasive breast cancer had SLN successfully identified and core biopsied. 487 had a benign SLN core biopsy and 427 (88 %) did not have metastases found in surgically excised SLN. Only 2 % of patients with an initial benign SLN core biopsy were found to have 2 or more LN macrometastases. 68 patients had a malignant SLN core biopsy and 52 % had 2 or more LN macrometastases. The total volume of LN metastases was higher in the group of patients who had an initial malignant SLN core biopsy (P < 0.001). CONCLUSIONS: Patients with a normal grey-scale ultrasound and benign SLN core biopsy are unlikely to have extensive axillary disease and may be ideally suited for axillary conservation. The decision to omit axillary LN dissection for patients with a malignant SLN core biopsy must be carefully considered because many will have undetected high-volume metastases.

Percutaneous removal of sentinel lymph nodes in a swine model using a breast lesion excision system and contrast-enhanced ultrasound.

OBJECTIVES: To investigate the feasibility of percutaneous removal of the entire sentinel lymph node (SLN) in an animal model using a breast lesion excision system after identifying these nodes using contrast-enhanced ultrasound (CEUS) and intradermal microbubbles. METHODS: Animal studies approval was obtained. SLNs were identified using CEUS and intradermal injection of microbubbles in two young pigs. Microbubbles were mixed with blue dye and injected around the mammary papillae to access lymphatic drainage to the superficial inguinal lymph nodes. When enhancing nodes were identified, the breast lesion excision system (BLES) was used to remove these nodes percutaneously. Both animals then underwent surgical lymph node dissection. Histopathological examination of all the samples was performed. RESULTS: Removal of the entire SLN was successful in three groins in the pigs. All three nodes were stained with blue dye. No other stained nodes were observed in the node dissection specimens. The nodal architecture of removed lymph nodes was well preserved on microscopy. There were no signs of excess trauma within the biopsy bed. CONCLUSION: The results obtained from the swine model demonstrated that it is feasible to remove the entire SLN percutaneously under the guidance of CEUS and microbubbles. KEY POINTS: Intradermal injection of microbubbles and CEUS can identify sentinel lymph nodes • Ultrasound could then guide percutaneous removal of intact and complete SLNs • We have shown this was feasible in pigs but not yet in humans • This technique may eventually have the potential to reduce futile SLN biopsies.

Preoperative needle biopsy of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasound in patients with breast cancer.

OBJECTIVE: The purpose of this study was to assess whether sentinel lymph nodes (SLNs) that undergo targeted needle biopsy after identification by contrast-enhanced ultrasound (CEUS) using intradermally injected microbubbles results in more node-positive breast cancer patients being diagnosed preoperatively. Furthermore, we sought to determine whether the addition of CEUS to gray-scale sonography of the axilla reduces the number of patients having axillary lymph node (ALN) dissection as a second procedure. SUBJECTS AND METHODS: Intradermal microbubble injection was performed in 136 breast cancer patients who had no abnormal ALNs on routine gray-scale axillary sonography. When an enhancing ALN was visualized, percutaneous sonography-guided fine-needle aspiration cytology or core needle biopsy was performed. Depending on the biopsy results, patients underwent SLN biopsy or ALN dissection. If the putative SLN biopsy was positive or a biopsy tract was seen in the excised SLN, the procedure was defined as successful. RESULTS: SLNs were identified and biopsied in 126 of the 136 cases (93%). Seventeen patients had positive sonography-guided biopsy results (13%) and were treated with immediate ALN dissection. In seven patients, the biopsied node was the only positive node. The remaining 109 patients underwent SLN biopsy. In nine cases (8%), a positive lymph node was identified. Four of these false-negative cases had only micrometastases. CONCLUSION: SLNs can be identified and biopsied using CEUS to increase the accuracy of preoperative axillary staging. If the needle biopsy result is negative, conventional SLN biopsy is indicated.

Influence of target-distractor neural similarity on working memory performance in older and younger adults.

According to the inhibitory deficit hypothesis, older adults often fail to selectively inhibit distractors and attend to relevant information in working memory, leading to poorer memory of target items but better recall of irrelevant distractors compared to younger adults. Here, we explored how neural similarity of activity patterns between relevant and irrelevant stimulus categories impacts memory performance. We found evidence that older adults may benefit from failing to inhibit distractors that are similar to targets, perhaps because sustained neural activation of distractors partially supports maintenance of targets when they share neural resources, allowing for better subsequent recognition of studied target items. We also found increased category-specific multivoxel pattern activity in medial temporal regions in younger compared to older adults as category similarity increased. We propose that this reduced category-specific activation in medial temporal regions in older adults may reflect more blended representations of all the information available in working memory.

The Transient Sea Level Response to External Forcing in CMIP6 Models.

Earth is warming and sea levels are rising as land-based ice is lost to melt, and oceans expand due to accumulation of heat. The pace of ice loss and steric expansion is linked to the intensity of warming. How much faster sea level will rise as climate warms is, however, highly uncertain and difficult to model. Here, we quantify the transient sea level sensitivity of the sea level budget in both models and observations. Models show little change in sensitivity to warming between the first and second half of the twenty-first century for most contributors. The exception is glaciers and ice caps (GIC) that have a greater sensitivity pre-2050 (2.8 ± 0.4 mm/yr/K) compared to later (0.7 ± 0.1 mm/yr/K). We attribute this change to the short response time of glaciers and their changing area over time. Model sensitivities of steric expansion (1.5 ± 0.2 mm/yr/K), and Greenland Ice Sheet mass loss (0.8 ± 0.2 mm/yr/K) are greater than, but still compatible with, corresponding estimates from historical data (1.4 ± 0.5 and 0.4 ± 0.2 mm/yr/K). Antarctic Ice Sheet (AIS) models tends to show lower rates of sea level rise (SLR) with warming (-0.0 ± 0.3 mm/yr/K) in contrast to historical estimates (0.4 ± 0.2 mm/yr/K). This apparent low bias in AIS sensitivity is only partly able to account for a similar low bias identified in the sensitivity of global mean sea level excluding GIC (3.1 ± 0.4 vs. 2.3 ± 0.4 mm/yr/K). The balance temperature, where SLR is zero, lies close to the pre-industrial value, implying that SLR can only be mitigated by substantial global cooling.

Preoperative sentinel node identification with ultrasound using microbubbles in patients with breast cancer.

OBJECTIVE: Sentinel lymph node (SLN) biopsy is the standard procedure for axillary staging in early breast cancer. Lymphatic imaging after peritumoral microbubble injection has been described in animal models. The aim of this study was to identify and localize SLNs preoperatively by contrast-enhanced sonography after intradermal injection of microbubbles in patients with breast cancer. SUBJECTS AND METHODS: Eighty consecutive consenting patients with primary breast cancer were recruited. Patients received a periareolar intradermal injection of microbubble contrast agent. Breast lymphatics were visualized by sonography and followed to the axilla to identify SLNs. A guidewire was deployed to localize the SLN. The next day, patients underwent standard tumor excision and SLN biopsy. RESULTS: In 71 (89%) of the 80 patients, SLNs were identified and guidewires were inserted. In these patients, operative findings using conventional radioisotope and blue dye techniques confirmed that the wired nodes were SLNs. Fourteen patients were found to have metastases in SLNs. In these patients, the SLNs were identified correctly and were localized with guidewires before surgery. CONCLUSION: SLNs may be identified and localized before surgery using contrast-enhanced sonography after injection of microbubbles.

Forensic Nursing Response to Victim-Administered Evidence Kits.

The International Association of Forensic Nurses has issued guidance in response to victim- or self-administered evidence kits after sexual assault.

Position Statement: Child Maltreatment: International Association of Forensic Nurses Board of Directors, 2019.

The International Association of Forensic Nurses has developed a Position Statement regarding child maltreatment. The Position Statement identifies the problem statement, association position, and rationale for interventions.

Risk behaviors in a rural community with a known point-source exposure to chronic wasting disease.

BACKGROUND: The emergence and continuing spread of Chronic Wasting Disease (CWD) in cervids has now reached 14 U.S. states, two Canadian provinces, and South Korea, producing a potential for transmission of CWD prions to humans and other animals globally. In 2005, CWD spread for the first time from the Midwest to more densely populated regions of the East Coast. As a result, a large cohort of individuals attending a wild game feast in upstate New York were exposed to a deer that was subsequently confirmed positive for CWD. METHODS: Eighty-one participants who ingested or otherwise were exposed to a deer with chronic wasting disease at a local New York State sportsman's feast were recruited for this study. Participants were administered an exposure questionnaire and agreed to follow-up health evaluations longitudinally over the next six years. RESULTS: Our results indicate two types of risks for those who attended the feast, a Feast Risk and a General Risk. The larger the number of risk factors, the greater the risk to human health if CWD is transmissible to humans. Long-term surveillance of feast participants exposed to CWD is ongoing. CONCLUSION: The risk data from this study provide a relative scale for cumulative exposure to CWD-infected tissues and surfaces, and those in the upper tiers of cumulative risk may be most at risk if CWD is transmissible to humans.

Older adults encode more, not less: evidence for age-related attentional broadening.

Previous work has shown that older adults attend to and implicitly remember more distracting information than young adults; however, it is unknown whether they show a corresponding decrease in implicit memory for targets in the presence of distracters. Using implicit memory tests, we asked whether older adults show a tradeoff in memory between targets and distracters. Here, young and older adults performed a selective attention task in which they were instructed to attend to target pictures and ignore superimposed distracter words. We measured priming for distracter words using fragment completion and for target pictures using naming time. Older adults showed greater priming for distracting words compared to young adults, but equivalent priming for target pictures. These results suggest that older adults have a broader attentional scope than young adults, encompassing both relevant and irrelevant information.

Leveraging older adults' susceptibility to distraction to improve memory for face-name associations.

Forgetting people's names is a common memory complaint among older adults and one that is consistent with experimental evidence of age-related decline in memory for face-name associations. Despite this difficulty intentionally forming face-name associations, a recent study demonstrated that older adults hyperbind distracting names and attended faces, which produces better learning of these face-name pairs when they reappear on a memory test (Weeks, Biss, Murphy, & Hasher, 2016). The current study explored whether this effect could be leveraged as an intervention to reduce older adults' forgetting of face-name associations, using a method previously shown to improve older adults' retention of a word list (Biss, Ngo, Hasher, Campbell, & Rowe, 2013). Twenty-five younger and 32 older adults studied 24 face-name pairs and were tested via immediate and delayed memory tests. During the 30-min retention interval, 10 of the face-name pairs reoccurred as distraction in an ostensibly unrelated face-judgment task, providing an opportunity to implicitly rehearse these pairs. Older adults showed reduced forgetting of repeated face-name pairs as well as improved recollection. Younger adults showed no reliable benefit. These findings indicate that useful distraction benefits older adults' memory for face-name associations, suggesting its potential utility as a memory intervention technique. (PsycINFO Database Record

Enhanced pre-operative axillary staging using intradermal microbubbles and contrast-enhanced ultrasound to detect and biopsy sentinel lymph nodes in breast cancer: a potential replacement for axillary surgery.

OBJECTIVE: To compare the experience of four UK Centres in the use of intradermal microbubbles and contrast enhanced ultrasound (CEUS) to pre-operatively identify and biopsy sentinel lymph nodes (SLN) in patients with breast cancer. METHODS: In all centres, breast cancer patients had a microbubble/CEUS SLN core biopsy prior to axillary surgery and patients in Centres 1 and 2 had a normal greyscale axillary ultrasound. Data were collected between 2010 and 2016; 1361 from Centre 1 (prospective, sequential), 376 from Centre 2 (retrospective, sequential), 121 from Centre 3 (retrospective, selected) and 48 from Centre 4 (prospective, selected). RESULTS: SLN were successfully core biopsied in 80% (Centre 1), 79.6% (Centre 2), 77.5% (Centre 3) and 88% (Centre 4). The sensitivities to identify all SLN metastases were 46.9% [95% confidence intervals (CI) (39.4-55.1)], 52.5% [95% CI (39.1-65.7)], 46.4% [95% CI (27.5-66.1)] and 45.5% [95% CI (16.7-76.6)], respectively. The specificities were 99.7% [95% CI (I98.9-100)], 98.1% [95% CI (94.5-99.6)], 100% [95% CI (93.2-100%)] and 96.3% [95% CI (81-99.9)], respectively.The negative predictive values were 87.0% [95% CI (84.3-89.3)], 84.5% [95% CI (78.4-89.5)], 86.9% [95% CI (82.4-90.3)] and 86.2% [95% CI (78.4-91.5)], respectively. At Centres 1 and 2, 12/730 (1.6%) and 7/181 (4%), respectively, of patients with a benign microbubble/CEUS SLN core biopsy had two or more lymph node (LN) macrometastases found at the end of primary surgical treatment. CONCLUSION: The identification and biopsy of SLN using CEUS is a reproducible technique. Advances in knowledge: In the era of axillary conservation, microbubble/CEUS SLN core biopsy has the potential to succeed surgical staging of the axilla.

Divided attention reduces resistance to distraction at encoding but not retrieval.

Older adults show implicit memory for previously seen distraction, an effect attributed to poor attentional control. It is unclear whether this effect results from lack of control over encoding during the distraction task, lack of retrieval constraint during the test task, or both. In the present study, we simulated poor distraction control in young adults using divided attention at encoding, at retrieval, at both times, or not at all. The encoding task was a 1-back task on pictures with distracting superimposed letter strings, some of which were words. The retrieval task was a word fragment completion task testing implicit memory for the distracting words. Attention was divided using an auditory odd digit detection task. Dividing attention at encoding, but not at retrieval, resulted in significant priming for distraction, which suggests that control over encoding processes is a primary determinant of distraction transfer in populations with low inhibitory control (e.g. older adults).

Face-name learning in older adults: a benefit of hyper-binding.

Difficulty remembering faces and corresponding names is a hallmark of cognitive aging, as is increased susceptibility to distraction. Given evidence that older adults spontaneously encode relationships between target pictures and simultaneously occurring distractors (a hyper-binding phenomenon), we asked whether memory for face-name pairs could be improved through prior exposure to faces presented with distractor names. In three experiments, young and older adults performed a selective attention task on faces while ignoring superimposed names. After a delay, they learned and were tested on face-name pairs that were either maintained or rearranged from the initial task but were not told of the connection between tasks. In each experiment, older but not younger participants showed better memory for maintained than for rearranged pairs, indicating that older adults' natural propensity to tacitly encode and bind relevant and irrelevant information can be employed to aid face-name memory performance.

Metal Ion Dependent Molecular Inclusion Chemistry: Inclusion of p-Toluenesulfonate and p-Nitrophenolate within the Structure of Coordinated 1,4,7,10-Tetrakis((S)-2-hydroxy-3-phenoxypropyl)-1,4,7,10-tetraazacyclododecane.

The pendant donor macrocyclic ligand 1,4,7,10-tetrakis((S)-2-hydroxy-3-phenoxypropyl)-1,4,7,10-tetraazacyclododecane ((S)-thphpc12) has been synthesized in quantitative yield from cyclen (1,4,7,10-tetraazacyclododecane) and (2S)-(+)-3-phenoxy-1,2-epoxypropane. An X-ray diffraction study supports the result of molecular orbital calculations in showing that complexation with hydrated cadmium(II) diperchlorate produces an approximately square-antiprismatic complex in which the metal ion is located between a plane containing the four nitrogen atoms and a plane containing the four oxygen atoms. As a consequence of this the four phenoxymethyl moieties, each attached to one of the four N-O chelate rings, juxtapose to form a substantial empty cavity allowing the complex to act as a molecular receptor. Inclusion complexes have been formed from this complex in which either a p-toluenesulfonate or p-nitrophenolate anion has entered the cavity. An X-ray crystallographic study of [Cd((S)-thphpc12)(p-toluenesulfonate)]ClO(4) shows that the guest anion is retained within the cavity by four hydrogen bonds to the group of hydroxyl moieties associated with the ligand. (13)C NMR and conductivity studies indicate that this inclusion complex retains its integrity in DMSO or DMF solution. Parallel studies have been conducted with [Pb((S)-thphpc12)](ClO(4))(2) indicating that the corresponding inclusion complexes are of lower stability.

The disruptive - and beneficial - effects of distraction on older adults' cognitive performance.

Older adults' decreased ability to inhibit irrelevant information makes them especially susceptible to the negative effects of simultaneously occurring distraction. For example, older adults are more likely than young adults to process distraction presented during a task, which can result in delayed response times, decreased reading comprehension, disrupted problem solving, and reduced memory for target information. However, there is also some evidence that the tendency to process distraction can actually facilitate older adults' performance when the distraction is congruent with the target information. For example, congruent distraction can speed response times, increase reading comprehension, benefit problem solving, and reduce forgetting in older adults. We review data showing that incongruent distraction can harm older adults' performance, as well as evidence suggesting that congruent distraction can play a supportive role for older adults by facilitating processing of target information. Potential applications of distraction processing are also discussed.

How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye.

BACKGROUND: Blue dye used for sentinel lymph node biopsy (SLNB) in breast cancer patients may cause prolonged skin discoloration at the site of injection. The aim of this study was to assess the duration of such skin discoloration. PATIENTS AND METHODS: 236 consecutive patients who had undergone breast conserving surgery and SLNB for breast cancer were reviewed prospectively from January 2007 to December 2009. RESULTS: Of the 236 patients, 2 had undergone bilateral surgery, and 41 had been examined in consecutive yearly reviews. Blue discoloration remained visible at the injection site after 12, 24, and > 36 months in 36.5, 23.6, and 8.6% of the patients, respectively. CONCLUSION: The use of patent blue for identification of the sentinel lymph node in patients undergoing breast cancer surgery may result in prolonged discoloration of the skin at the injection site.