Sotrovimab restores neutralization against current Omicron subvariants in patients with blood cancer.

Wu et al. report that patients with hematologic malignancies have reduced immunity against SARS-CoV-2 Omicron subvariants and Sotrovimab retains neutralizing capacity against all tested Omicron subvariants.

Documenting a Reduction in Signing Space in Nicaraguan Sign Language Using Depth and Motion Capture.

In this paper, we use motion tracking technology to document the birth of a brand new language: Nicaraguan Sign Language. Languages are dynamic entities that undergo change and growth through use, transmission, and learning, but the earliest stages of this process are generally difficult to observe as most languages have been used and passed down for many generations. Here, we observe a rare case of language emergence: the earliest stages of the new sign language in Nicaragua. By comparing the signing of the oldest and youngest signers of Nicaraguan Sign Language, we can track how the language itself is changing. Using motion tracking technology, we document a decrease in the size of articulatory space of Nicaraguan Sign Language signers over time. The reduction in articulatory space in Nicaraguan Sign appears to be the joint product of several decades of use and repeated transmission of this new language.

Late-Stage Metastatic Melanoma Emerges through a Diversity of Evolutionary Pathways.

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma. SIGNIFICANCE: Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA. See related commentary by Shain, p. 1294. This article is highlighted in the In This Issue feature, p. 1275.

Therapy Exercises Following Cranial Cruciate Ligament Repair in Dogs.

Therapy exercises can help to optimize the outcome for dogs following cranial cruciate ligament repair surgery. This article focuses on land exercises that can be done with minimal equipment in home or in clinic. The first 8 weeks of recovery are covered including therapy and basic exercises for each phase.

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer.

Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886), we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralizing antibody titers (NAbTs) using a live virus microneutralization assay against wild-type (WT), Delta, and Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titers and T cell responses after the fourth vaccine dose increased compared with that after the third vaccine dose. Patients who received B cell-depleting therapies within the 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study.

CAPTURE (NCT03226886) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable neutralizing antibody titers (NAbT) against SARS-CoV-2 variants of concern (VOCs) vs wildtype (WT). Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT vs solid cancers against both WT and VOCs. In comparison with individuals without cancer, patients with haematological, but not solid, malignancies had reduced NAb responses. Seroconversion showed poor concordance with NAbT against VOCs. Prior SARS-CoV-2 infection boosted NAb response including against VOCs, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T-cell responses were detected in 80% of patients, and were comparable between vaccines or cancer types. Our results have implications for the management of cancer patients during the ongoing COVID-19 pandemic.

Structural biases that children bring to language learning: A cross-cultural look at gestural input to homesign.

Linguistic input has an immediate effect on child language, making it difficult to discern whatever biases children may bring to language-learning. To discover these biases, we turn to deaf children who cannot acquire spoken language and are not exposed to sign language. These children nevertheless produce gestures, called homesigns, which have structural properties found in natural language. We ask whether these properties can be traced to gestures produced by hearing speakers in Nicaragua, a gesture-rich culture, and in the USA, a culture where speakers rarely gesture without speech. We studied 7 homesigning children and hearing family members in Nicaragua, and 4 in the USA. As expected, family members produced more gestures without speech, and longer gesture strings, in Nicaragua than in the USA. However, in both cultures, homesigners displayed more structural complexity than family members, and there was no correlation between individual homesigners and family members with respect to structural complexity. The findings replicate previous work showing that the gestures hearing speakers produce do not offer a model for the structural aspects of homesign, thus suggesting that children bring biases to construct, or learn, these properties to language-learning. The study also goes beyond the current literature in three ways. First, it extends homesign findings to Nicaragua, where homesigners received a richer gestural model than USA homesigners. Moreover, the relatively large numbers of gestures in Nicaragua made it possible to take advantage of more sophisticated statistical techniques than were used in the original homesign studies. Second, the study extends the discovery of complex noun phrases to Nicaraguan homesign. The almost complete absence of complex noun phrases in the hearing family members of both cultures provides the most convincing evidence to date that homesigners, and not their hearing family members, are the ones who introduce structural properties into homesign. Finally, by extending the homesign phenomenon to Nicaragua, the study offers insight into the gestural precursors of an emerging sign language. The findings shed light on the types of structures that an individual can introduce into communication before that communication is shared within a community of users, and thus sheds light on the roots of linguistic structure.

Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study.

Coronavirus disease 2019 (COVID-19) antiviral response in a pan-tumor immune monitoring (CAPTURE) ( NCT03226886 ) is a prospective cohort study of COVID-19 immunity in patients with cancer. Here we evaluated 585 patients following administration of two doses of BNT162b2 or AZD1222 vaccines, administered 12 weeks apart. Seroconversion rates after two doses were 85% and 59% in patients with solid and hematological malignancies, respectively. A lower proportion of patients had detectable titers of neutralizing antibodies (NAbT) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) versus wild-type (WT) SARS-CoV-2. Patients with hematological malignancies were more likely to have undetectable NAbT and had lower median NAbT than those with solid cancers against both SARS-CoV-2 WT and VOC. By comparison with individuals without cancer, patients with hematological, but not solid, malignancies had reduced neutralizing antibody (NAb) responses. Seroconversion showed poor concordance with NAbT against VOC. Previous SARS-CoV-2 infection boosted the NAb response including against VOC, and anti-CD20 treatment was associated with undetectable NAbT. Vaccine-induced T cell responses were detected in 80% of patients and were comparable between vaccines or cancer types. Our results have implications for the management of patients with cancer during the ongoing COVID-19 pandemic.

The communicative importance of agent-backgrounding: Evidence from homesign and Nicaraguan Sign Language.

Some concepts are more essential for human communication than others. In this paper, we investigate whether the concept of agent-backgrounding is sufficiently important for communication that linguistic structures for encoding this concept are present in young sign languages. Agent-backgrounding constructions serve to reduce the prominence of the agent - the English passive sentence a book was knocked over is an example. Although these constructions are widely attested cross-linguistically, there is little prior research on the emergence of such devices in new languages. Here we studied how agent-backgrounding constructions emerge in Nicaraguan Sign Language (NSL) and adult homesign systems. We found that NSL signers have innovated both lexical and morphological devices for expressing agent-backgrounding, indicating that conveying a flexible perspective on events has deep communicative value. At the same time, agent-backgrounding devices did not emerge at the same time as agentive devices. This result suggests that agent-backgrounding does not have the same core cognitive status as agency. The emergence of agent-backgrounding morphology appears to depend on receiving a linguistic system as input in which linguistic devices for expressing agency are already well-established.

Rehabilitation Therapy in Perioperative Pain Management.

Physical agent modalities can be effective in the perioperative period for controlling pain and inflammation. This article presents research-based evidence to support the use of these modalities in pain management and to reduce the use of pain medications, including opioids. The mechanism of action, applications, contraindications, and adverse effects of cryotherapy, pulsed electromagnetic field therapy, transcutaneous electrical nerve stimulation, and laser therapy are reviewed. Incorporation of 1 or more of these therapies in anesthesia pain management protocols can improve outcomes and reduce potential drug side effects.

The emergence of the formal category "symmetry" in a new sign language.

Logical properties such as negation, implication, and symmetry, despite the fact that they are foundational and threaded through the vocabulary and syntax of known natural languages, pose a special problem for language learning. Their meanings are much harder to identify and isolate in the child's everyday interaction with referents in the world than concrete things (like spoons and horses) and happenings and acts (like running and jumping) that are much more easily identified, and thus more easily linked to their linguistic labels (spoon, horse, run, jump). Here we concentrate attention on the category of symmetry [a relation R is symmetrical if and only if (iff) for all x, y: if R(x,y), then R(y,x)], expressed in English by such terms as similar, marry, cousin, and near After a brief introduction to how symmetry is expressed in English and other well-studied languages, we discuss the appearance and maturation of this category in Nicaraguan Sign Language (NSL). NSL is an emerging language used as the primary, daily means of communication among a population of deaf individuals who could not acquire the surrounding spoken language because they could not hear it, and who were not exposed to a preexisting sign language because there was none available in their community. Remarkably, these individuals treat symmetry, in both semantic and syntactic regards, much as do learners exposed to a previously established language. These findings point to deep human biases in the structures underpinning and constituting human language.

Generating a lexicon without a language model: Do words for number count?

Homesigns are communication systems created by deaf individuals without access to conventional linguistic input. To investigate how homesign gestures for number function in short-term memory compared to homesign gestures for objects, actions, or attributes, we conducted memory span tasks with adult homesigners in Nicaragua, and with comparison groups of unschooled hearing Spanish speakers and deaf Nicaraguan Sign Language signers. There was no difference between groups in recall of gestures or words for objects, actions or attributes; homesign gestures therefore can function as word units in short-term memory. However, homesigners showed poorer recall of numbers than the other groups. Unlike the other groups, increasing the numerical value of the to-be-remembered quantities negatively affected recall in homesigners, but not controls. When developed without linguistic input, gestures for number do not seem to function as summaries of the cardinal values of the sets (four), but rather as indexes of items within a set (one-one-one-one).

Alternative therapies in veterinary dermatology.

This article presents an overview of alternative therapies for skin disorders including traditional Chinese medicine (acupuncture and Chinese herbs), homeopathy, and Western herbs and plant extracts. The medical and veterinary literature on the aforementioned modalities will be reviewed with a focus on reduction of inflammation and pruritus of the skin and ear canal in the canine species. Clinical application and potential adverse effects will also be included when available.

Numerosity and number signs in deaf Nicaraguan adults.

What abilities are entailed in being numerate? Certainly, one is the ability to hold the exact quantity of a set in mind, even as it changes, and even after its members can no longer be perceived. Is counting language necessary to track and reproduce exact quantities? Previous work with speakers of languages that lack number words involved participants only from non-numerate cultures. Deaf Nicaraguan adults all live in a richly numerate culture, but vary in counting ability, allowing us to experimentally differentiate the contribution of these two factors. Thirty deaf and 10 hearing participants performed 11 one-to-one matching and counting tasks. Results suggest that immersion in a numerate culture is not enough to make one fully numerate. A memorized sequence of number symbols is required, though even an unconventional, iconic system is sufficient. Additionally, we find that within a numerate culture, the ability to track precise quantities can be acquired in adulthood.